US-MULT-250253
WARNING: Serious Infections, Mortality, Malignancies, Major Adverse Cardiovascular Events, and Thrombosis
‡Clinical remission does not mean drug-free remission or complete absence of disease activity.
ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; bDMARD=biologic disease‑modifying antirheumatic drug; CRP=C‑reactive protein; DAS28‑CRP=28‑joint disease activity score using C‑reactive protein; NPA=National Prescription Audit; NSP=National Sales Perspectives; tsDMARD=targeted synthetic disease-modifying antirheumatic drug.
INDICATION
RINVOQ is indicated for the treatment of adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to one or more tumor necrosis factor (TNF) blockers.
Limitations of Use: RINVOQ is not recommended for use in combination with other Janus kinase (JAK) inhibitors, biologic disease-modifying antirheumatic drugs (bDMARDs), or with potent immunosuppressants such as azathioprine and cyclosporine.
‡As of 08/2025: In PsA, ~6.4 years maximum exposure (~3.6 years median) to RINVOQ 15 mg; in AS, ~3.8 years maximum exposure (~1.8 years median) to RINVOQ 15 mg; in nr-axSpA, ~2.3 years maximum exposure (~1.0 years median) to RINVOQ 15 mg.9
§RINVOQ is on a preferred tier or otherwise has preferred status on the plan’s formulary.
||Coverage requirements and benefit designs vary by payer and may change over time. Please consult with payers directly for the most current reimbursement policies.
ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; AS=ankylosing spondylitis; CRP=C-reactive protein; csDMARD=conventional synthetic disease-modifying antirheumatic drug; DAS28-CRP=28 joint disease activity score using C-reactive protein; GCA=giant cell arteritis; max=maximum; nr-axSpA=non-radiographic axial spondyloarthritis; PsA=psoriatic arthritis; TNFi=tumor necrosis factor inhibitor.
Please see Important Safety Information, including BOXED WARNING on Serious Infections, Mortality, Malignancies, Major Adverse Cardiovascular Events, and Thrombosis, below.
Primary Endpoint Results (Week 12 or 14)
*NRI-MI used for SELECT-SWITCH. †P≤0.001 RINVOQ vs placebo or MTX. ‡P<0.001 RINVOQ vs HUMIRA. §P=0.0001; Week 1 analyses were not controlled for multiplicity; P-values obtained through nominal statistical testing.
RINVOQ is indicated for moderate to severe RA in adult TNFi‑IR patients.
RINVOQ has a Boxed Warning on Serious Infections, Mortality, Malignancy, Major Adverse Cardiovascular Events, and Thrombosis.
HUMIRA is indicated in adults with moderate to severe active RA.
HUMIRA has a Boxed Warning for Serious Infections and Malignancy.
Details about these Boxed Warnings and other risks can be found throughout.
Clinical decisions regarding treatment selection should take into account all relevant information, including full benefit/risk profiles in each product’s PI.
SELECT-BEYOND (STUDY RA-V):1,7 24‐week, randomized, double-blind, placebo‐controlled study of 499 adult patients with moderate to severe RA who had an inadequate response or intolerance to bDMARDs.
SELECT-COMPARE (STUDY RA-IV):1,12 48‐week, randomized, double-blind, active‐comparator‐controlled study of 1629 adult patients with moderate to severe RA who had an inadequate response to MTX.
SELECT-MONOTHERAPY (STUDY RA-II):1,3 14‐week, randomized, double‐blind, active comparator‐controlled study of 648 adult patients with moderate to severe RA who had an inadequate response to MTX.
SELECT-SWITCH:13 12‐week, randomized, double‐blind, active‐comparator‐controlled study of 491 adult patients with moderate to severe RA who did not respond to 1 TNFi (non-adalimumab).
ACR=American College of Rheumatology; bDMARD=biologic disease-modifying antirheumatic drug; cMTX=continued methotrexate; csDMARD=conventional synthetic disease-modifying antirheumatic drug; DAS28‑CRP=28‑joint disease activity score using C-reactive protein; IR=intolerance or inadequate response; LDA=low disease activity; MTX=methotrexate; NRI=nonresponder imputation; NRI-MI=nonresponder imputation incorporating multiple imputation; PI=prescribing information; RA=rheumatoid arthritis; TNFi=tumor necrosis factor inhibitor.
RINVOQ is indicated for the treatment of adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to one or more tumor necrosis factor (TNF) blockers.
Limitations of Use: RINVOQ is not recommended for use in combination with other Janus kinase (JAK) inhibitors, biologic disease-modifying antirheumatic drugs (bDMARDs), or with potent immunosuppressants such as azathioprine and cyclosporine.
REFERENCES:
SELECT-BEYOND
Adults with moderately to severely active RA who had an inadequate response or intolerance to bDMARDs1
RINVOQ is indicated for TNFi-IR patients1
Upadacitinib 30 mg is not an approved dose.
aStarting at Week 24, initiation of or change in corticosteroids, NSAIDs, acetaminophen, and csDMARDs was permitted. Patients not achieving response criteria ≥20% improvement in SJC and TJC at 2 consecutive visits were removed from the study.4,5
bFollowing a protocol amendment, all patients in the long-term extension received UPA 15 mg QD, including those previously on UPA 30 mg.8
PRIMARY ENDPOINT1
RANKED SECONDARY ENDPOINTS6,7
At Week 12:
SELECT PRESPECIFIED NONRANKED ENDPOINTS7
DATA LIMITATIONS
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
BASELINE CHARACTERISTICS6
| MEAN (SD) OR N (%) | PBO + csDMARDs n=169 | RINVOQ 15 mg + csDMARDs n=164 |
|---|---|---|
| Female, n (%) | 143 (85) | 137 (84) |
| Age (years), mean (SD) | 57.6 (11.4) | 56.3 (11.3) |
| Duration since RA diagnosis (years), mean (SD) | 14.5 (9.2) | 12.4 (9.4) |
| RF+ and/or ACPA+, n (%) | 128 (76) | 131 (80) |
| csDMARD use at baseline* | ||
| - MTX alone,† n (%) | 122 (73) | 118 (73) |
| - MTX plus other csDMARD,‡ n (%) | 17 (10) | 19 (12) |
| - MTX dose§ (mg), mean (SD) | 16.6 (4.7) | 17.3 (4.6) |
| - csDMARD other than MTX, n (%) | 29 (17) | 24 (15) |
| - Missing, n | 1 | 3 |
| Prior bDMARD exposure | ||
| - 1, n (%) | 83 (49) | 86 (52) |
| - 2, n (%) | 46 (27) | 40 (24) |
| - ≥3, n (%) | 40 (24) | 38 (23) |
| Inadequate response or intolerance to ≥1 anti-TNF drug | 152 (90) | 146 (89) |
| - Lack of efficacy with ≥1 bDMARD | 159 (94) | 146 (89) |
| - Lack of efficacy with ≥1 anti–IL-6 | 30 (18) | 27 (16) |
| Oral glucocorticoid use, n (%) | 74 (44) | 83 (51) |
| - Oral glucocorticoid dosell (mg), mean (SD) | 6.3 (2.4) | 5.7 (2.4) |
| TJC68, mean (SD) | 28.5 (15.3) | 27.8 (16.3) |
| SJC66, mean (SD) | 16.3 (9.6) | 17.0 (10.8) |
| PtGA (0–100 mm VAS), mean (SD) | 66.3 (22.7) | 67.2 (19.6) |
| PhGA (0–100 mm VAS), mean (SD) | 66.9 (16.9) | 68.7 (16.6) |
| Pain (0–100 mm VAS), mean (SD) | 68.9 (21.0) | 68.2 (19.8) |
| hsCRP (mg/L), mean (SD) | 16.3 (21.1) | 16.2 (18.6) |
| DAS28-CRP, mean (SD) | 5.8 (1.0) | 5.9 (1.0) |
| HAQ-DI, mean (SD) | 1.6 (0.6) | 1.7 (0.6) |
| CDAI, mean (SD) | 41.0 (13.3) | 41.7 (13.3) |
| SDAI, mean (SD) | 42.6 (13.9) | 43.3 (13.8) |
*Oral or parenteral methotrexate (7.5–25 mg per week).
†Data available for 168 patients receiving placebo and 161 patients receiving RINVOQ 15 mg.
‡All combinations allowed except MTX and leflunomide.
§Mean MTX dose calculated only for patients receiving MTX.
‖Based on prednisone equivalent.
ACPA=anti‑citrullinated protein antibodies; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; bDMARD=biologic disease‑modifying antirheumatic drug; CDAI=Clinical Disease Activity Index; CR=clinical remission; CRP=C‑reactive protein; csDMARD=conventional synthetic disease‑modifying antirheumatic drug; DAS28-CRP=28-joint disease activity score using C-reactive protein; DAS28-ESR=28-joint disease activity score using erythrocyte sedimentation rate; ESR=erythrocyte sedimentation rate; HAQ‑DI=Health Assessment Questionnaire Disability Index; hsCRP=high‑sensitivity C‑reactive protein; IL-6=interleukin 6; IR=intolerance or inadequate response; LDA=low disease activity; MTX=methotrexate; NSAID=nonsteroidal anti‑inflammatory drug; PBO=placebo; PhGA=Physician’s Global Assessment; PtGA=patient global assessment; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=Simplified Disease Activity Index; SF‑36 (PCS)=36‑item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; UPA=upadacitinib; VAS=visual analog scale.
REFERENCES:
SELECT-COMPARE
Adults with moderately to severely active RA who had an inadequate response to MTX1
RINVOQ is indicated for TNFi-IR patients1
aX-ray imaging was performed at these time points; Week 14 for nonresponder patients, who were rescued.2,3
bRescue criteria: At Weeks 14, 18, and 22, if <20% improvement in TJC and SJC vs baseline; at Week 26, all remaining PBO patients were switched to RINVOQ, and patients receiving RINVOQ or active comparator were switched to active comparator or RINVOQ, respectively, if CDAI >10.2
cStarting at Week 26, initiation or change in background RA medication(s), including corticosteroids, NSAIDs, or acetaminophen was permitted.4
dStarting at Week 48, patients who failed to show ≥20% improvement in TJC and SJC compared to baseline at 2 consecutive visits were removed from the study.5
eAt Week 48, initiation or change in csDMARDs was allowed; however, not all patients received background MTX.5
fPatients continued treatment with UPA or active comparator in a blinded manner until the last patient completed the Week 48 visit and received open-label treatment thereafter.8
PRIMARY ENDPOINT1
SELECT RANKED SECONDARY ENDPOINTS2
At Week 12 vs placebo + MTX:
At Week 12 vs active comparator + MTX:
At Week 26 vs placebo + MTX:
SELECT PRESPECIFIED NONRANKED ENDPOINTS3,9,10
DATA LIMITATIONS
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
SELECT-COMPARE was not designed to evaluate the efficacy of active comparator + MTX vs placebo + MTX. No conclusions regarding this comparison can be made.
BASELINE CHARACTERISTICS3
| MEAN (SD) OR N (%) | PBO + MTX n=651 | RINVOQ 15 mg QD + MTX n=651 |
|---|---|---|
| Female, n (%) | 512 (79) | 521 (80) |
| Age (years), mean (SD) | 54 (12) | 54 (12) |
| Duration since RA diagnosis (years), mean (SD) | 8 (8) | 8 (8) |
| RF+ and/or anti-CCP+, n (%) | 571 (88) | 566 (87) |
| MTX dose (mg/week), mean (SD) | 16.8 (3.8) | 17.0 (4.2) |
| Prior bDMARD use, n (%) | 63 (10) | 54 (8) |
| Oral glucocorticoid use, n (%) | 392 (60) | 388 (60) |
| - Dose (mg),* mean (SD) | 6.3 (2.4) | 6.2 (2.3) |
| TJC68, mean (SD) | 26 (14) | 26 (15) |
| SJC66, mean (SD) | 16 (9) | 17 (10) |
| PtGA (0–100 mm VAS), mean (SD) | 64 (21) | 64 (22) |
| PhGA (0–100 mm VAS), mean (SD) | 66 (18) | 66 (17) |
| Pain (0–100 mm VAS), mean (SD) | 65 (21) | 66 (21) |
| hsCRP (mg/L), mean (SD) | 18 (22) | 18 (22) |
| DAS28-CRP, mean (SD) | 5.8 (0.9) | 5.8 (1.0) |
| HAQ-DI, mean (SD) | 1.6 (0.6) | 1.6 (0.6) |
| CDAI, mean (SD) | 40 (13) | 40 (13) |
| SDAI, mean (SD) | 41.8 (13.3) | 41.5 (13.6) |
| mTSS, mean (SD) | 36 (52) | 34 (50) |
| - JE score, mean (SD) | 17 (27) | 17 (26) |
| - JSN score, mean (SD) | 19 (26) | 18 (25) |
*Based on prednisone equivalent.
ACPA=anti-citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; bDMARD=biologic disease‑modifying antirheumatic drug; CCP=cyclic citrullinated peptide; CDAI=Clinical Disease Activity Index; CR=clinical remission; CRP=C‑reactive protein; csDMARD=conventional synthetic disease-modifying antirheumatic drug; DAS28-CRP=28-joint disease activity score using C-reactive protein; DAS28-ESR=28-joint disease activity score using erythrocyte sedimentation rate; EOW=every other week; ESR=erythrocyte sedimentation rate; HAQ‑DI=Health Assessment Questionnaire Disability Index; hsCRP=high-sensitivity C‑reactive protein; IR=intolerance or inadequate response; JE=joint erosion; JSN=joint space narrowing; LDA=low disease activity; mTSS=modified total Sharp score; MTX=methotrexate; NSAID=nonsteroidal anti-inflammatory drug; PBO=placebo; PhGA=Physician's Global Assessment; PtGA=patient global assessment; QD=once per day; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=Simplified Disease Activity Index; SF‑36 (PCS)=36-item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; UPA=upadacitinib; VAS=visual analog scale.
REFERENCES:
SELECT-MONOTHERAPY
Adults with moderately to severely active RA who had an inadequate response to MTX1
RINVOQ is indicated for TNFi-IR patients1
Upadacitinib 30 mg is not an approved dose.
aPatients on cMTX were randomized to receive either RINVOQ 15 mg or upadacitinib 30 mg at Week 14.3
bStarting at Week 26, patients who did not achieve CDAI ≤10 could have initiated or adjusted corticosteroids, NSAIDs, acetaminophen, or ≤2 csDMARDs. Patients who failed to show ≥20% improvement in TJC and SJC compared to baseline at 2 consecutive visits were removed from the study.5
cFollowing a protocol amendment, all patients in the long-term extension received UPA 15 mg QD, including those previously on UPA 30 mg.4
PRIMARY ENDPOINT1
RANKED SECONDARY ENDPOINTS3,6
At Week 14:
SELECT PRESPECIFIED NONRANKED ENDPOINTS3,6
DATA LIMITATIONS
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
BASELINE CHARACTERISTICS3
| MEAN (SD) OR N (%) | cMTX n=216 | RINVOQ 15 mg QD n=217 |
|---|---|---|
| Female, n (%) | 179 (83) | 174 (80) |
| Age (years), mean (SD) | 55.3 (11.1) | 54.5 (12.2) |
| Duration since RA diagnosis (years), mean (SD) | 5.8 (6.6) | 7.5 (8.9) |
| RF+ and/or ACPA+, n (%) | 169 (78) | 172 (79) |
| Prior MTX dose* (mg/week), mean (SD) | 16.7 (4.4) | 16.8 (4.2) |
| Prior MTX duration (years), mean (SD) | 3.3 (3.9) | 3.8 (4.8) |
| Oral glucocorticoid use, n (%) | 115 (53) | 114 (53) |
| - Oral glucocorticoid dose† (mg), mean (SD) | 6.2 (2.6) | 6.1 (2.5) |
| TJC68, mean (SD) | 25.2 (16.0) | 24.5 (15.1) |
| SJC66, mean (SD) | 16.9 (11.5) | 16.4 (10.9) |
| PtGA (0–100 mm VAS), mean (SD) | 59.6 (21.8) | 62.2 (22.3) |
| PhGA (0–100 mm VAS), mean (SD) | 62.1 (17.5) | 65.7 (18.5) |
| Pain (0–100 mm VAS), mean (SD) | 62.5 (21.3) | 62.3 (22.5) |
| hsCRP (mg/L), mean (SD) | 14.5 (17.3) | 14.0 (16.5) |
| DAS28-CRP, mean (SD) | 5.6 (1.0) | 5.6 (0.9) |
| HAQ-DI, mean (SD) | 1.5 (0.7) | 1.5 (0.7) |
| CDAI, mean (SD) | 37.8 (14.4) | 38.0 (13.1) |
| SDAI, mean (SD) | 39.2 (14.6) | 39.4 (13.4) |
*Prior to receiving study drug. In the control arm, patients continued prior MTX dose as blinded study drug.3
†Prednisone equivalent.
ACPA=anti‑citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; CDAI=Clinical Disease Activity Index; cMTX=continuous methotrexate; csDMARD=conventional synthetic disease‑modifying antirheumatic drug; CR=clinical remission; CRP=C‑reactive protein; DAS28-CRP=28-joint disease activity score using C-reactive protein; DAS28-ESR=28-joint disease activity score using erythrocyte sedimentation rate; ESR=erythrocyte sedimentation rate; HAQ‑DI=Health Assessment Questionnaire Disability Index; hsCRP=high-sensitivity C‑reactive protein; IR=intolerance or inadequate response; LDA=low disease activity; MTX=methotrexate; NSAID=nonsteroidal anti‑inflammatory drug; PhGA=Physician’s Global Assessment; PtGA=patient global assessment; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=Simplified Disease Activity Index; SF‑36 (PCS)=36-item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; UPA=upadacitinib; VAS=visual analog scale.
REFERENCES:
SELECT-SWITCH
Head-to-head study powered to evaluate superiority of RINVOQ vs HUMIRA (adalimumab) in RA patients who had inadequate response or intolerance to 1 TNFi2
A 12-week, randomized, double-blind, active-comparator–controlled study of 491 adult patients with moderate to severe RA who did not respond to 1 TNFi (non-adalimumab). Designed to evaluate superiority of continuing TNFi therapy with HUMIRA (adalimumab) vs switching to RINVOQ (upadacitinib).
PRIMARY ENDPOINT2
SELECT RANKED SECONDARY ENDPOINTS2
At Week 12 vs HUMIRA:
SELECT PRESPECIFIED NONRANKED ENDPOINTS2
At all visits:
| MEAN (SD) Unless otherwise stated |
RINVOQ 15 mg QD + MTX (n=245) | HUMIRA 40 mg EOW + MTX n=246* |
|---|---|---|
| Parameter | ||
| Age (years) | 55.3 (12.7) | 55.9 (12.5) |
| Age ≥65 years, n (%) | 57 (23.3) | 72 (29.3) |
| Female, n (%) | 189 (77.1) | 191 (77.6) |
| BMI (kg/m2) | 29.4 (6.5) | 28.8 (7.0) |
| RA duration since diagnosis (years) | 10.1 (8.5) (n=244) | 10.3 (9.3) |
| Disease Characteristics | ||
| DAS28-CRP | 5.7 (0.8) (n=235) | 5.7 (0.8) (n=236) |
| DAS28-ESR | 6.3 (0.9) (n=234) | 6.4 (0.9) (n=235) |
| TJC68 | 22.4 (12.3) | 22.8 (12.6) |
| SJC66 | 15.5 (6.6) | 15.9 (8.3) |
| hsCRP (mg/L) | 16.8 (25.4) (n=245) | 14.0 (17.6) |
| ESR (mm/hr) | 37.1 (23.4) (n=243) | 38.9 (24.4) (n=245) |
| PtGA (0–10 NRS) | 7.1 (1.9) (n=235) | 7.4 (1.9) (n=236) |
| PhGA (0–10 NRS) | 7.0 (1.6) | 6.9 (1.6) |
| Pain (0–10 NRS) | 7.4 (1.9) | 7.4 (1.9) (n=232) |
| HAQ-DI | 1.6 (0.6) (n=234) | 1.6 (0.6) (n=234) |
| FACIT-Fatigue | 26.8 (11.5) (n=234) | 26.8 (10.5) (n=233) |
| Concomitant Therapies | ||
| Patients receiving oral corticosteroid at baseline, n (%) | 99 (40.4) | 100 (40.7) |
| Oral steroid dose (prednisone equivalent) at baseline (mg/day) | 6.4 (2.7) (n=99) | 6.7 (3.2) (n=100) |
| MTX dose at baseline (mg/week), median | 15.0 | 15.0 (n=245) |
| NSAIDs | 128 (52.2) | 111 (45.1) |
| Patient History, n (%) | ||
| HZ vaccination | 35 (14.6) | 31 (12.8) |
| History of VTE | 2 (0.8) | 2 (0.8) |
| History of CV event | 18 (7.3) | 11 (4.5) |
| Number of CV risk factorsa, n (%) | ||
| 0 | 72 (29.4) | 65 (26.4) |
| 1 | 94 (38.4) | 107 (43.5) |
| 2 | 58 (23.7) | 61 (24.8) |
| 3+ | 21 (8.6) | 13 (5.3) |
| CV risk factors at baseline, n (%) | ||
| Hypertension | 90 (36.7) | 85 (34.6) |
| Diabetes mellitus | 6 (2.4) | 2 (0.8) |
| History of tobacco/nicotine use (current/former) | 89 (36.3) | 77 (31.3) |
| Elevated LDL-Cb | 42 (17.1) | 65 (26.4) |
| Low HDL-Cc | 36 (14.7) | 32 (13.0) |
| Reason for discontinuation of prior TNFi, n (%) | ||
| Intolerance | 25 (10.2) | 27 (11.0) |
| Inadequate response | 220 (89.8) | 219 (89.0) |
| Type of inadequate response to prior TNFi, n (%) | ||
| Primary nonresponder | 121 (55.8) | 115 (54.0) |
| Secondary nonresponder | 96 (44.2) | 98 (46.0) |
| Missing | 3 | 6 |
| Prior TNFi administered, n (%) | ||
| Etanercept | 165 (67.3) | 170 (69.1) |
| Certolizumab | 40 (16.3) | 35 (14.2) |
| Golimumab | 24 (9.8) | 21 (8.5) |
| Infliximab | 15 (6.1) | 13 (5.3) |
| Adalimumab† | 0 | 1 (0.4) |
*Patients entered the study while receiving a stable dose of MTX (15–25 mg/week). MTX was not considered an ancillary drug in the study.2
†Protocol deviations.2
aCV risk factors included CV event, hypertension, diabetes mellitus, tobacco/nicotine use, elevated LDL-C, and lowered HDL‑C.
b≥3.36 mmol/L (ie, >129.9 mg/dL).
c<1.034 mmol/L (ie, <18.6 mg/dL).
ACR=American College of Rheumatology; BMI=body mass index; CDAI=Clinical Disease Activity Index; CRP=C-reactive protein; CV=cardiovascular; DAS28-CRP=Disease Activity Score in 28 joints using C-reactive protein; DAS28-ESR=28-joint Disease Activity Score using erythrocyte sedimentation rate; EOW=every other week; ESR=erythrocyte sedimentation rate; FACIT-Fatigue=Functional Assessment of Chronic Illness Therapy-Fatigue; HAQ-DI=Health Assessment Questionnaire-Disability Index; HDL-C=high-density lipoprotein cholesterol; hsCRP=high-sensitivity C-reactive protein; HZ=herpes zoster; IR=intolerance or inadequate response; LDA=low disease activity; LDL-C=low-density lipoprotein cholesterol; MACE=major adverse cardiovascular event; MTX=methotrexate; NSAID=nonsteroidal anti-inflammatory drug; PhGA=Physician's Global Assessment; PtGA=patient global assessment; primary nonresponder=patient who did not respond to prior TNFi treatment; QD=once daily; RA=rheumatoid arthritis; SC=subcutaneous; SD=standard deviation; SDAI=Simplified Disease Activity Index; secondary nonresponder=patient who initially responded to prior TNFi treatment but lost response over time; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; VTE=venous thromboembolism.
REFERENCES:
SELECT-EARLY
Adults with moderately to severely active RA who were MTX‑naïve1
RINVOQ is indicated for TNFi-IR patients1
Upadacitinib 30 mg is not an approved dose.
aInitially 947 patients were randomized in the study, but 2 patients were never dosed.
bX-ray images of hands and feet obtained at these time points.2
cStarting at Week 12, patients with ≤20% improvement in TJC and SJC compared to baseline at 2 consecutive visits continued blinded therapy and optimized background RA medications (corticosteroids, NSAIDs, and/or low‑potency analgesics).3,4
dAt Week 26, patients with CDAI ≤2.8 continued their original study drug; background medications (NSAIDs, corticosteroids, and/or low‑potency analgesics, and csDMARDs) were optimized in patients with CDAI >2.8 but ≥20% improvement in TJC and SJC; among patients with CDAI >2.8 and <20% improvement in TJC and SJC, RINVOQ 15 mg or upadacitinib 30 mg were added by re‑randomization according to 1:1 ratio for those initially randomized to MTX, and MTX was added for those initially randomized to RINVOQ 15 mg or upadacitinib 30 mg.2,5
eStarting at Week 48, patients who did not achieve ≥20% improvement in both TJC and SJC at 2 consecutive visits were removed from the study. Initiation of or change in background RA medications (NSAIDs, corticosteroids, low-potency analgesics, and csDMARDs; not all patients received background MTX) is allowed at anytime during Period 2.6
fFollowing a protocol amendment, all patients in the long-term extension who were previously receiving UPA 30 mg received RINVOQ 15 mg.11
PRIMARY ENDPOINT1
RANKED SECONDARY ENDPOINTS3,8
At Week 12:
At Week 24:
SELECT PRESPECIFIED NONRANKED ENDPOINTS2,3,9,10
DATA LIMITATIONS
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
BASELINE CHARACTERISTICS3
| MEAN (SD) OR N (%) | MTX n=314 | RINVOQ 15 mg QD n=317 |
|---|---|---|
| Female, n (%) | 240 (76) | 241 (76) |
| Age (years), mean (SD) | 53.3 (12.9) | 51.9 (12.6) |
| Duration since RA diagnosis (years), mean (SD) | 2.6 (5.1) | 2.9 (5.4) |
| RF+ and/or ACPA+, n (%) | 255 (81) | 279 (88) |
| MTX exposure, n (%) | 19 (6) | 30 (9.5) |
| csDMARD exposure, n (%) | 79 (25) | 80 (25) |
| Oral glucocorticoid use, n (%) | 163 (52) | 147 (46) |
| - Dose (mg),* mean (SD) | 6.4 (2.4) | 6.4 (3.1) |
| TJC68, mean (SD) | 26.4 (16.2) | 25.4 (14.4) |
| SJC66, mean (SD) | 16.9 (10.6) | 16.9 (10.4) |
| PtGA (0–100 mm VAS), mean (SD) | 65.8 (21.5) | 66.6 (22.0) |
| PhGA (0–100 mm VAS), mean (SD) | 68.7 (16.5) | 67.1 (17.0) |
| Pain (0–100 mm VAS), mean (SD) | 65.7 (21.5) | 68.4 (20.6) |
| hsCRP (mg/L), mean (SD) | 21.2 (22.1) | 23.0 (27.4) |
| DAS28-CRP, mean (SD) | 5.9 (1.0) | 5.9 (1.0) |
| HAQ-DI, mean (SD) | 1.6 (0.7) | 1.6 (0.7) |
| CDAI, mean (SD) | 40.5 (13.3) | 40.4 (13.3) |
| SDAI, mean (SD) | 42.6 (14.0) | 42.7 (13.9) |
| mTSS, mean (SD) | 13.3 (30.6) | 18.1 (38.2) |
| - Erosion Score, mean (SD) | 6.1 (15.5) | 8.6 (19.3) |
| - Joint Space Narrowing Score, mean (SD) | 7.2 (16.2) | 9.6 (20.1) |
*Prednisone equivalent dose in patients receiving oral glucocorticoids at baseline.
ACPA=anti-citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; CDAI=Clinical Disease Activity Index; CR=clinical remission; CRP=C-reactive protein; csDMARD=conventional synthetic disease-modifying antirheumatic drug; DAS28-CRP=28-joint disease activity score using C-reactive protein; HAQ-DI=Health Assessment Questionnaire Disability Index; hsCRP=high-sensitivity C-reactive protein; IR=intolerance or inadequate response; JE=joint erosion; JSN=joint space narrowing; LDA=low disease activity; mTSS=modified total Sharp score; MTX=methotrexate; NSAID=nonsteroidal anti-inflammatory drug; PhGA=Physician's Global Assessment; PtGA=patient global assessment; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=Simplified Disease Activity Index; SF-36 (PCS)=36-item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; UPA=upadacitinib; VAS=visual analog scale.
REFERENCES:
SELECT-NEXT
Adults with moderately to severely active RA who had an inadequate response to csDMARD(s)1
RINVOQ is indicated for TNFi-IR patients1
Upadacitinib 30 mg is not an approved dose.
aStarting at Week 24, patients who did not achieve CDAI ≤10 could have initiated or adjusted corticosteroids, NSAIDs, acetaminophen, or ≤2 csDMARDs. Patients who failed to show ≥20% improvement in TJC and SJC compared to baseline at 2 consecutive visits were removed from the study.4
bFollowing a protocol amendment, all patients in the long-term extension received UPA 15 mg QD, including those previously on UPA 30 mg.7
PRIMARY ENDPOINT1
RANKED SECONDARY ENDPOINTS5,6
At Week 12:
SELECT PRESPECIFIED NONRANKED ENDPOINTS6
DATA LIMITATIONS
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
BASELINE CHARACTERISTICS3
| MEAN (SD) OR N (%) | PBO + csDMARDs n=221 | RINVOQ 15 mg QD + csDMARDs n=221 |
|---|---|---|
| Female, n (%) | 166 (75) | 182 (82) |
| Age (years), mean (SD) | 56.0 (12.2) | 55.3 (11.5) |
| Duration since RA diagnosis (years), mean (SD) | 7.2 (7.5) | 7.3 (7.9) |
| RF+ and/or ACPA+, n (%) | 181 (82) | 184 (83) |
| csDMARD use at baseline | ||
| - MTX alone, n (%) | 141 (64) | 122 (55) |
| - MTX plus other csDMARD, n (%) | 49 (22) | 47 (21) |
| - csDMARD other than MTX, n (%) | 30 (14) | 51 (23) |
| - Missing, n (%) | 1 (<1) | 1 (<1) |
| Prior bDMARD exposure, n (%) | 29 (13) | 27 (12) |
| Oral glucocorticoid use, n (%) | 106 (48) | 96 (43) |
| - Oral glucocorticoid dose* (mg), mean (SD) | 6.3 (2.6) | 6.0 (2.4) |
| TJC68, mean (SD) | 24.7 (15.0) | 25.2 (13.8) |
| SJC66, mean (SD) | 15.4 (9.2) | 16.0 (10.0) |
| PtGA (0–100 mm VAS), mean (SD) | 60.3 (20.5) | 63.1 (21.9) |
| PhGA (0–100 mm VAS), mean (SD) | 64.4 (17.7) | 64.3 (16.2) |
| Pain (0–100 mm VAS), mean (SD) | 61.5 (20.8) | 64.1 (19.5) |
| hsCRP (mg/L), mean (SD) | 12.6 (14.0) | 16.6 (19.2) |
| DAS28-CRP, mean (SD) | 5.6 (0.8) | 5.7 (1.0) |
| HAQ-DI, mean (SD) | 1.4 (0.6) | 1.5 (0.6) |
| CDAI, mean (SD) | 37.8 (11.8) | 38.3 (11.9) |
| SDAI, mean (SD) | 39.0 (11.9) | 39.9 (12.5) |
*Based on prednisone equivalent.
ACPA=anti-citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; bDMARD=biologic disease-modifying antirheumatic drug; CDAI=Clinical Disease Activity Index; CR=clinical remission; CRP=C-reactive protein; csDMARD=conventional synthetic disease-modifying antirheumatic drug; DAS28-CRP=28-joint disease activity score using C-reactive protein; HAQ-DI=Health Assessment Questionnaire Disability Index; hsCRP=high-sensitivity C-reactive protein; IR=intolerance or inadequate response; JE=joint erosion; JSN=joint space narrowing; LDA=low disease activity; MTX=methotrexate; NSAID=nonsteroidal anti-inflammatory drug; PBO=placebo; PhGA=Physician's Global Assessment; PtGA=patient global assessment; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=Simplified Disease Activity Index; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; UPA=upadacitinib; VAS=visual analog scale.
REFERENCES:
US-RNQR-260103
SELECT-BEYOND
Adults with moderately to severely active RA who had an inadequate response or intolerance to bDMARDs1
RINVOQ is indicated for TNFi-IR patients1
Upadacitinib 30 mg is not an approved dose.
aStarting at Week 24, initiation of or change in corticosteroids, NSAIDs, acetaminophen, and csDMARDs was permitted. Patients not achieving response criteria ≥20% improvement in SJC and TJC at 2 consecutive visits were removed from the study.4,5
bFollowing a protocol amendment, all patients in the long-term extension received UPA 15 mg QD, including those previously on UPA 30 mg.8
PRIMARY ENDPOINT1
RANKED SECONDARY ENDPOINTS6,7
At Week 12:
SELECT PRESPECIFIED NONRANKED ENDPOINTS7
DATA LIMITATIONS
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
BASELINE CHARACTERISTICS6
| MEAN (SD) OR N (%) | PBO + csDMARDs n=169 | RINVOQ 15 mg + csDMARDs n=164 |
|---|---|---|
| Female, n (%) | 143 (85) | 137 (84) |
| Age (years), mean (SD) | 57.6 (11.4) | 56.3 (11.3) |
| Duration since RA diagnosis (years), mean (SD) | 14.5 (9.2) | 12.4 (9.4) |
| RF+ and/or ACPA+, n (%) | 128 (76) | 131 (80) |
| csDMARD use at baseline* | ||
| - MTX alone,† n (%) | 122 (73) | 118 (73) |
| - MTX plus other csDMARD,‡ n (%) | 17 (10) | 19 (12) |
| - MTX dose§ (mg), mean (SD) | 16.6 (4.7) | 17.3 (4.6) |
| - csDMARD other than MTX, n (%) | 29 (17) | 24 (15) |
| - Missing, n | 1 | 3 |
| Prior bDMARD exposure | ||
| - 1, n (%) | 83 (49) | 86 (52) |
| - 2, n (%) | 46 (27) | 40 (24) |
| - ≥3, n (%) | 40 (24) | 38 (23) |
| Inadequate response or intolerance to ≥1 anti-TNF drug | 152 (90) | 146 (89) |
| - Lack of efficacy with ≥1 bDMARD | 159 (94) | 146 (89) |
| - Lack of efficacy with ≥1 anti–IL-6 | 30 (18) | 27 (16) |
| Oral glucocorticoid use, n (%) | 74 (44) | 83 (51) |
| - Oral glucocorticoid dosell (mg), mean (SD) | 6.3 (2.4) | 5.7 (2.4) |
| TJC68, mean (SD) | 28.5 (15.3) | 27.8 (16.3) |
| SJC66, mean (SD) | 16.3 (9.6) | 17.0 (10.8) |
| PtGA (0–100 mm VAS), mean (SD) | 66.3 (22.7) | 67.2 (19.6) |
| PhGA (0–100 mm VAS), mean (SD) | 66.9 (16.9) | 68.7 (16.6) |
| Pain (0–100 mm VAS), mean (SD) | 68.9 (21.0) | 68.2 (19.8) |
| hsCRP (mg/L), mean (SD) | 16.3 (21.1) | 16.2 (18.6) |
| DAS28-CRP, mean (SD) | 5.8 (1.0) | 5.9 (1.0) |
| HAQ-DI, mean (SD) | 1.6 (0.6) | 1.7 (0.6) |
| CDAI, mean (SD) | 41.0 (13.3) | 41.7 (13.3) |
| SDAI, mean (SD) | 42.6 (13.9) | 43.3 (13.8) |
*Oral or parenteral methotrexate (7.5–25 mg per week).
†Data available for 168 patients receiving placebo and 161 patients receiving RINVOQ 15 mg.
‡All combinations allowed except MTX and leflunomide.
§Mean MTX dose calculated only for patients receiving MTX.
‖Based on prednisone equivalent.
ACPA=anti‑citrullinated protein antibodies; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; bDMARD=biologic disease‑modifying antirheumatic drug; CDAI=Clinical Disease Activity Index; CR=clinical remission; CRP=C‑reactive protein; csDMARD=conventional synthetic disease‑modifying antirheumatic drug; DAS28-CRP=28-joint disease activity score using C-reactive protein; DAS28-ESR=28-joint disease activity score using erythrocyte sedimentation rate; ESR=erythrocyte sedimentation rate; HAQ‑DI=Health Assessment Questionnaire Disability Index; hsCRP=high‑sensitivity C‑reactive protein; IL-6=interleukin 6; IR=intolerance or inadequate response; LDA=low disease activity; MTX=methotrexate; NSAID=nonsteroidal anti‑inflammatory drug; PBO=placebo; PhGA=Physician’s Global Assessment; PtGA=patient global assessment; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=Simplified Disease Activity Index; SF‑36 (PCS)=36‑item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; UPA=upadacitinib; VAS=visual analog scale.
REFERENCES:
SELECT-COMPARE
Adults with moderately to severely active RA who had an inadequate response to MTX1
RINVOQ is indicated for TNFi-IR patients1
aX-ray imaging was performed at these time points; Week 14 for nonresponder patients, who were rescued.2,3
bRescue criteria: At Weeks 14, 18, and 22, if <20% improvement in TJC and SJC vs baseline; at Week 26, all remaining PBO patients were switched to RINVOQ, and patients receiving RINVOQ or active comparator were switched to active comparator or RINVOQ, respectively, if CDAI >10.2
cStarting at Week 26, initiation or change in background RA medication(s), including corticosteroids, NSAIDs, or acetaminophen was permitted.4
dStarting at Week 48, patients who failed to show ≥20% improvement in TJC and SJC compared to baseline at 2 consecutive visits were removed from the study.5
eAt Week 48, initiation or change in csDMARDs was allowed; however, not all patients received background MTX.5
fPatients continued treatment with UPA or active comparator in a blinded manner until the last patient completed the Week 48 visit and received open-label treatment thereafter.8
PRIMARY ENDPOINT1
SELECT RANKED SECONDARY ENDPOINTS2
At Week 12 vs placebo + MTX:
At Week 12 vs active comparator + MTX:
At Week 26 vs placebo + MTX:
SELECT PRESPECIFIED NONRANKED ENDPOINTS3,9,10
DATA LIMITATIONS
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
SELECT-COMPARE was not designed to evaluate the efficacy of active comparator + MTX vs placebo + MTX. No conclusions regarding this comparison can be made.
BASELINE CHARACTERISTICS3
| MEAN (SD) OR N (%) | PBO + MTX n=651 | RINVOQ 15 mg QD + MTX n=651 |
|---|---|---|
| Female, n (%) | 512 (79) | 521 (80) |
| Age (years), mean (SD) | 54 (12) | 54 (12) |
| Duration since RA diagnosis (years), mean (SD) | 8 (8) | 8 (8) |
| RF+ and/or anti-CCP+, n (%) | 571 (88) | 566 (87) |
| MTX dose (mg/week), mean (SD) | 16.8 (3.8) | 17.0 (4.2) |
| Prior bDMARD use, n (%) | 63 (10) | 54 (8) |
| Oral glucocorticoid use, n (%) | 392 (60) | 388 (60) |
| - Dose (mg),* mean (SD) | 6.3 (2.4) | 6.2 (2.3) |
| TJC68, mean (SD) | 26 (14) | 26 (15) |
| SJC66, mean (SD) | 16 (9) | 17 (10) |
| PtGA (0–100 mm VAS), mean (SD) | 64 (21) | 64 (22) |
| PhGA (0–100 mm VAS), mean (SD) | 66 (18) | 66 (17) |
| Pain (0–100 mm VAS), mean (SD) | 65 (21) | 66 (21) |
| hsCRP (mg/L), mean (SD) | 18 (22) | 18 (22) |
| DAS28-CRP, mean (SD) | 5.8 (0.9) | 5.8 (1.0) |
| HAQ-DI, mean (SD) | 1.6 (0.6) | 1.6 (0.6) |
| CDAI, mean (SD) | 40 (13) | 40 (13) |
| SDAI, mean (SD) | 41.8 (13.3) | 41.5 (13.6) |
| mTSS, mean (SD) | 36 (52) | 34 (50) |
| - JE score, mean (SD) | 17 (27) | 17 (26) |
| - JSN score, mean (SD) | 19 (26) | 18 (25) |
*Based on prednisone equivalent.
ACPA=anti-citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; bDMARD=biologic disease‑modifying antirheumatic drug; CCP=cyclic citrullinated peptide; CDAI=Clinical Disease Activity Index; CR=clinical remission; CRP=C‑reactive protein; csDMARD=conventional synthetic disease-modifying antirheumatic drug; DAS28-CRP=28-joint disease activity score using C-reactive protein; DAS28-ESR=28-joint disease activity score using erythrocyte sedimentation rate; EOW=every other week; ESR=erythrocyte sedimentation rate; HAQ‑DI=Health Assessment Questionnaire Disability Index; hsCRP=high-sensitivity C‑reactive protein; IR=intolerance or inadequate response; JE=joint erosion; JSN=joint space narrowing; LDA=low disease activity; mTSS=modified total Sharp score; MTX=methotrexate; NSAID=nonsteroidal anti-inflammatory drug; PBO=placebo; PhGA=Physician's Global Assessment; PtGA=patient global assessment; QD=once per day; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=Simplified Disease Activity Index; SF‑36 (PCS)=36-item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; UPA=upadacitinib; VAS=visual analog scale.
REFERENCES:
SELECT-MONOTHERAPY
Adults with moderately to severely active RA who had an inadequate response to MTX1
RINVOQ is indicated for TNFi-IR patients1
Upadacitinib 30 mg is not an approved dose.
aPatients on cMTX were randomized to receive either RINVOQ 15 mg or upadacitinib 30 mg at Week 14.3
bStarting at Week 26, patients who did not achieve CDAI ≤10 could have initiated or adjusted corticosteroids, NSAIDs, acetaminophen, or ≤2 csDMARDs. Patients who failed to show ≥20% improvement in TJC and SJC compared to baseline at 2 consecutive visits were removed from the study.5
cFollowing a protocol amendment, all patients in the long-term extension received UPA 15 mg QD, including those previously on UPA 30 mg.4
PRIMARY ENDPOINT1
RANKED SECONDARY ENDPOINTS3,6
At Week 14:
SELECT PRESPECIFIED NONRANKED ENDPOINTS3,6
DATA LIMITATIONS
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
BASELINE CHARACTERISTICS3
| MEAN (SD) OR N (%) | cMTX n=216 | RINVOQ 15 mg QD n=217 |
|---|---|---|
| Female, n (%) | 179 (83) | 174 (80) |
| Age (years), mean (SD) | 55.3 (11.1) | 54.5 (12.2) |
| Duration since RA diagnosis (years), mean (SD) | 5.8 (6.6) | 7.5 (8.9) |
| RF+ and/or ACPA+, n (%) | 169 (78) | 172 (79) |
| Prior MTX dose* (mg/week), mean (SD) | 16.7 (4.4) | 16.8 (4.2) |
| Prior MTX duration (years), mean (SD) | 3.3 (3.9) | 3.8 (4.8) |
| Oral glucocorticoid use, n (%) | 115 (53) | 114 (53) |
| - Oral glucocorticoid dose† (mg), mean (SD) | 6.2 (2.6) | 6.1 (2.5) |
| TJC68, mean (SD) | 25.2 (16.0) | 24.5 (15.1) |
| SJC66, mean (SD) | 16.9 (11.5) | 16.4 (10.9) |
| PtGA (0–100 mm VAS), mean (SD) | 59.6 (21.8) | 62.2 (22.3) |
| PhGA (0–100 mm VAS), mean (SD) | 62.1 (17.5) | 65.7 (18.5) |
| Pain (0–100 mm VAS), mean (SD) | 62.5 (21.3) | 62.3 (22.5) |
| hsCRP (mg/L), mean (SD) | 14.5 (17.3) | 14.0 (16.5) |
| DAS28-CRP, mean (SD) | 5.6 (1.0) | 5.6 (0.9) |
| HAQ-DI, mean (SD) | 1.5 (0.7) | 1.5 (0.7) |
| CDAI, mean (SD) | 37.8 (14.4) | 38.0 (13.1) |
| SDAI, mean (SD) | 39.2 (14.6) | 39.4 (13.4) |
*Prior to receiving study drug. In the control arm, patients continued prior MTX dose as blinded study drug.3
†Prednisone equivalent.
ACPA=anti‑citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; CDAI=Clinical Disease Activity Index; cMTX=continuous methotrexate; csDMARD=conventional synthetic disease‑modifying antirheumatic drug; CR=clinical remission; CRP=C‑reactive protein; DAS28-CRP=28-joint disease activity score using C-reactive protein; DAS28-ESR=28-joint disease activity score using erythrocyte sedimentation rate; ESR=erythrocyte sedimentation rate; HAQ‑DI=Health Assessment Questionnaire Disability Index; hsCRP=high-sensitivity C‑reactive protein; IR=intolerance or inadequate response; LDA=low disease activity; MTX=methotrexate; NSAID=nonsteroidal anti‑inflammatory drug; PhGA=Physician’s Global Assessment; PtGA=patient global assessment; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=Simplified Disease Activity Index; SF‑36 (PCS)=36-item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; UPA=upadacitinib; VAS=visual analog scale.
REFERENCES:
SELECT-SWITCH
Head-to-head study powered to evaluate superiority of RINVOQ vs HUMIRA (adalimumab) in RA patients who had inadequate response or intolerance to 1 TNFi2
A 12-week, randomized, double-blind, active-comparator–controlled study of 491 adult patients with moderate to severe RA who did not respond to 1 TNFi (non-adalimumab). Designed to evaluate superiority of continuing TNFi therapy with HUMIRA (adalimumab) vs switching to RINVOQ (upadacitinib).
PRIMARY ENDPOINT2
SELECT RANKED SECONDARY ENDPOINTS2
At Week 12 vs HUMIRA:
SELECT PRESPECIFIED NONRANKED ENDPOINTS2
At all visits:
| MEAN (SD) Unless otherwise stated |
RINVOQ 15 mg QD + MTX (n=245) | HUMIRA 40 mg EOW + MTX n=246* |
|---|---|---|
| Parameter | ||
| Age (years) | 55.3 (12.7) | 55.9 (12.5) |
| Age ≥65 years, n (%) | 57 (23.3) | 72 (29.3) |
| Female, n (%) | 189 (77.1) | 191 (77.6) |
| BMI (kg/m2) | 29.4 (6.5) | 28.8 (7.0) |
| RA duration since diagnosis (years) | 10.1 (8.5) (n=244) | 10.3 (9.3) |
| Disease Characteristics | ||
| DAS28-CRP | 5.7 (0.8) (n=235) | 5.7 (0.8) (n=236) |
| DAS28-ESR | 6.3 (0.9) (n=234) | 6.4 (0.9) (n=235) |
| TJC68 | 22.4 (12.3) | 22.8 (12.6) |
| SJC66 | 15.5 (6.6) | 15.9 (8.3) |
| hsCRP (mg/L) | 16.8 (25.4) (n=245) | 14.0 (17.6) |
| ESR (mm/hr) | 37.1 (23.4) (n=243) | 38.9 (24.4) (n=245) |
| PtGA (0–10 NRS) | 7.1 (1.9) (n=235) | 7.4 (1.9) (n=236) |
| PhGA (0–10 NRS) | 7.0 (1.6) | 6.9 (1.6) |
| Pain (0–10 NRS) | 7.4 (1.9) | 7.4 (1.9) (n=232) |
| HAQ-DI | 1.6 (0.6) (n=234) | 1.6 (0.6) (n=234) |
| FACIT-Fatigue | 26.8 (11.5) (n=234) | 26.8 (10.5) (n=233) |
| Concomitant Therapies | ||
| Patients receiving oral corticosteroid at baseline, n (%) | 99 (40.4) | 100 (40.7) |
| Oral steroid dose (prednisone equivalent) at baseline (mg/day) | 6.4 (2.7) (n=99) | 6.7 (3.2) (n=100) |
| MTX dose at baseline (mg/week), median | 15.0 | 15.0 (n=245) |
| NSAIDs | 128 (52.2) | 111 (45.1) |
| Patient History, n (%) | ||
| HZ vaccination | 35 (14.6) | 31 (12.8) |
| History of VTE | 2 (0.8) | 2 (0.8) |
| History of CV event | 18 (7.3) | 11 (4.5) |
| Number of CV risk factorsa, n (%) | ||
| 0 | 72 (29.4) | 65 (26.4) |
| 1 | 94 (38.4) | 107 (43.5) |
| 2 | 58 (23.7) | 61 (24.8) |
| 3+ | 21 (8.6) | 13 (5.3) |
| CV risk factors at baseline, n (%) | ||
| Hypertension | 90 (36.7) | 85 (34.6) |
| Diabetes mellitus | 6 (2.4) | 2 (0.8) |
| History of tobacco/nicotine use (current/former) | 89 (36.3) | 77 (31.3) |
| Elevated LDL-Cb | 42 (17.1) | 65 (26.4) |
| Low HDL-Cc | 36 (14.7) | 32 (13.0) |
| Reason for discontinuation of prior TNFi, n (%) | ||
| Intolerance | 25 (10.2) | 27 (11.0) |
| Inadequate response | 220 (89.8) | 219 (89.0) |
| Type of inadequate response to prior TNFi, n (%) | ||
| Primary nonresponder | 121 (55.8) | 115 (54.0) |
| Secondary nonresponder | 96 (44.2) | 98 (46.0) |
| Missing | 3 | 6 |
| Prior TNFi administered, n (%) | ||
| Etanercept | 165 (67.3) | 170 (69.1) |
| Certolizumab | 40 (16.3) | 35 (14.2) |
| Golimumab | 24 (9.8) | 21 (8.5) |
| Infliximab | 15 (6.1) | 13 (5.3) |
| Adalimumab† | 0 | 1 (0.4) |
*Patients entered the study while receiving a stable dose of MTX (15–25 mg/week). MTX was not considered an ancillary drug in the study.2
†Protocol deviations.2
aCV risk factors included CV event, hypertension, diabetes mellitus, tobacco/nicotine use, elevated LDL-C, and lowered HDL‑C.
b≥3.36 mmol/L (ie, >129.9 mg/dL).
c<1.034 mmol/L (ie, <18.6 mg/dL).
ACR=American College of Rheumatology; BMI=body mass index; CDAI=Clinical Disease Activity Index; CRP=C-reactive protein; CV=cardiovascular; DAS28-CRP=Disease Activity Score in 28 joints using C-reactive protein; DAS28-ESR=28-joint Disease Activity Score using erythrocyte sedimentation rate; EOW=every other week; ESR=erythrocyte sedimentation rate; FACIT-Fatigue=Functional Assessment of Chronic Illness Therapy-Fatigue; HAQ-DI=Health Assessment Questionnaire-Disability Index; HDL-C=high-density lipoprotein cholesterol; hsCRP=high-sensitivity C-reactive protein; HZ=herpes zoster; IR=intolerance or inadequate response; LDA=low disease activity; LDL-C=low-density lipoprotein cholesterol; MACE=major adverse cardiovascular event; MTX=methotrexate; NSAID=nonsteroidal anti-inflammatory drug; PhGA=Physician's Global Assessment; PtGA=patient global assessment; primary nonresponder=patient who did not respond to prior TNFi treatment; QD=once daily; RA=rheumatoid arthritis; SC=subcutaneous; SD=standard deviation; SDAI=Simplified Disease Activity Index; secondary nonresponder=patient who initially responded to prior TNFi treatment but lost response over time; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; VTE=venous thromboembolism.
REFERENCES:
SELECT-EARLY
Adults with moderately to severely active RA who were MTX‑naïve1
RINVOQ is indicated for TNFi-IR patients1
Upadacitinib 30 mg is not an approved dose.
aInitially 947 patients were randomized in the study, but 2 patients were never dosed.
bX-ray images of hands and feet obtained at these time points.2
cStarting at Week 12, patients with ≤20% improvement in TJC and SJC compared to baseline at 2 consecutive visits continued blinded therapy and optimized background RA medications (corticosteroids, NSAIDs, and/or low‑potency analgesics).3,4
dAt Week 26, patients with CDAI ≤2.8 continued their original study drug; background medications (NSAIDs, corticosteroids, and/or low‑potency analgesics, and csDMARDs) were optimized in patients with CDAI >2.8 but ≥20% improvement in TJC and SJC; among patients with CDAI >2.8 and <20% improvement in TJC and SJC, RINVOQ 15 mg or upadacitinib 30 mg were added by re‑randomization according to 1:1 ratio for those initially randomized to MTX, and MTX was added for those initially randomized to RINVOQ 15 mg or upadacitinib 30 mg.2,5
eStarting at Week 48, patients who did not achieve ≥20% improvement in both TJC and SJC at 2 consecutive visits were removed from the study. Initiation of or change in background RA medications (NSAIDs, corticosteroids, low-potency analgesics, and csDMARDs; not all patients received background MTX) is allowed at anytime during Period 2.6
fFollowing a protocol amendment, all patients in the long-term extension who were previously receiving UPA 30 mg received RINVOQ 15 mg.11
PRIMARY ENDPOINT1
RANKED SECONDARY ENDPOINTS3,8
At Week 12:
At Week 24:
SELECT PRESPECIFIED NONRANKED ENDPOINTS2,3,9,10
DATA LIMITATIONS
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
BASELINE CHARACTERISTICS3
| MEAN (SD) OR N (%) | MTX n=314 | RINVOQ 15 mg QD n=317 |
|---|---|---|
| Female, n (%) | 240 (76) | 241 (76) |
| Age (years), mean (SD) | 53.3 (12.9) | 51.9 (12.6) |
| Duration since RA diagnosis (years), mean (SD) | 2.6 (5.1) | 2.9 (5.4) |
| RF+ and/or ACPA+, n (%) | 255 (81) | 279 (88) |
| MTX exposure, n (%) | 19 (6) | 30 (9.5) |
| csDMARD exposure, n (%) | 79 (25) | 80 (25) |
| Oral glucocorticoid use, n (%) | 163 (52) | 147 (46) |
| - Dose (mg),* mean (SD) | 6.4 (2.4) | 6.4 (3.1) |
| TJC68, mean (SD) | 26.4 (16.2) | 25.4 (14.4) |
| SJC66, mean (SD) | 16.9 (10.6) | 16.9 (10.4) |
| PtGA (0–100 mm VAS), mean (SD) | 65.8 (21.5) | 66.6 (22.0) |
| PhGA (0–100 mm VAS), mean (SD) | 68.7 (16.5) | 67.1 (17.0) |
| Pain (0–100 mm VAS), mean (SD) | 65.7 (21.5) | 68.4 (20.6) |
| hsCRP (mg/L), mean (SD) | 21.2 (22.1) | 23.0 (27.4) |
| DAS28-CRP, mean (SD) | 5.9 (1.0) | 5.9 (1.0) |
| HAQ-DI, mean (SD) | 1.6 (0.7) | 1.6 (0.7) |
| CDAI, mean (SD) | 40.5 (13.3) | 40.4 (13.3) |
| SDAI, mean (SD) | 42.6 (14.0) | 42.7 (13.9) |
| mTSS, mean (SD) | 13.3 (30.6) | 18.1 (38.2) |
| - Erosion Score, mean (SD) | 6.1 (15.5) | 8.6 (19.3) |
| - Joint Space Narrowing Score, mean (SD) | 7.2 (16.2) | 9.6 (20.1) |
*Prednisone equivalent dose in patients receiving oral glucocorticoids at baseline.
ACPA=anti-citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; CDAI=Clinical Disease Activity Index; CR=clinical remission; CRP=C-reactive protein; csDMARD=conventional synthetic disease-modifying antirheumatic drug; DAS28-CRP=28-joint disease activity score using C-reactive protein; HAQ-DI=Health Assessment Questionnaire Disability Index; hsCRP=high-sensitivity C-reactive protein; IR=intolerance or inadequate response; JE=joint erosion; JSN=joint space narrowing; LDA=low disease activity; mTSS=modified total Sharp score; MTX=methotrexate; NSAID=nonsteroidal anti-inflammatory drug; PhGA=Physician's Global Assessment; PtGA=patient global assessment; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=Simplified Disease Activity Index; SF-36 (PCS)=36-item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; UPA=upadacitinib; VAS=visual analog scale.
REFERENCES:
SELECT-NEXT
Adults with moderately to severely active RA who had an inadequate response to csDMARD(s)1
RINVOQ is indicated for TNFi-IR patients1
Upadacitinib 30 mg is not an approved dose.
aStarting at Week 24, patients who did not achieve CDAI ≤10 could have initiated or adjusted corticosteroids, NSAIDs, acetaminophen, or ≤2 csDMARDs. Patients who failed to show ≥20% improvement in TJC and SJC compared to baseline at 2 consecutive visits were removed from the study.4
bFollowing a protocol amendment, all patients in the long-term extension received UPA 15 mg QD, including those previously on UPA 30 mg.7
PRIMARY ENDPOINT1
RANKED SECONDARY ENDPOINTS5,6
At Week 12:
SELECT PRESPECIFIED NONRANKED ENDPOINTS6
DATA LIMITATIONS
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
BASELINE CHARACTERISTICS3
| MEAN (SD) OR N (%) | PBO + csDMARDs n=221 | RINVOQ 15 mg QD + csDMARDs n=221 |
|---|---|---|
| Female, n (%) | 166 (75) | 182 (82) |
| Age (years), mean (SD) | 56.0 (12.2) | 55.3 (11.5) |
| Duration since RA diagnosis (years), mean (SD) | 7.2 (7.5) | 7.3 (7.9) |
| RF+ and/or ACPA+, n (%) | 181 (82) | 184 (83) |
| csDMARD use at baseline | ||
| - MTX alone, n (%) | 141 (64) | 122 (55) |
| - MTX plus other csDMARD, n (%) | 49 (22) | 47 (21) |
| - csDMARD other than MTX, n (%) | 30 (14) | 51 (23) |
| - Missing, n (%) | 1 (<1) | 1 (<1) |
| Prior bDMARD exposure, n (%) | 29 (13) | 27 (12) |
| Oral glucocorticoid use, n (%) | 106 (48) | 96 (43) |
| - Oral glucocorticoid dose* (mg), mean (SD) | 6.3 (2.6) | 6.0 (2.4) |
| TJC68, mean (SD) | 24.7 (15.0) | 25.2 (13.8) |
| SJC66, mean (SD) | 15.4 (9.2) | 16.0 (10.0) |
| PtGA (0–100 mm VAS), mean (SD) | 60.3 (20.5) | 63.1 (21.9) |
| PhGA (0–100 mm VAS), mean (SD) | 64.4 (17.7) | 64.3 (16.2) |
| Pain (0–100 mm VAS), mean (SD) | 61.5 (20.8) | 64.1 (19.5) |
| hsCRP (mg/L), mean (SD) | 12.6 (14.0) | 16.6 (19.2) |
| DAS28-CRP, mean (SD) | 5.6 (0.8) | 5.7 (1.0) |
| HAQ-DI, mean (SD) | 1.4 (0.6) | 1.5 (0.6) |
| CDAI, mean (SD) | 37.8 (11.8) | 38.3 (11.9) |
| SDAI, mean (SD) | 39.0 (11.9) | 39.9 (12.5) |
*Based on prednisone equivalent.
ACPA=anti-citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; bDMARD=biologic disease-modifying antirheumatic drug; CDAI=Clinical Disease Activity Index; CR=clinical remission; CRP=C-reactive protein; csDMARD=conventional synthetic disease-modifying antirheumatic drug; DAS28-CRP=28-joint disease activity score using C-reactive protein; HAQ-DI=Health Assessment Questionnaire Disability Index; hsCRP=high-sensitivity C-reactive protein; IR=intolerance or inadequate response; JE=joint erosion; JSN=joint space narrowing; LDA=low disease activity; MTX=methotrexate; NSAID=nonsteroidal anti-inflammatory drug; PBO=placebo; PhGA=Physician's Global Assessment; PtGA=patient global assessment; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=Simplified Disease Activity Index; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; UPA=upadacitinib; VAS=visual analog scale.
REFERENCES:
US-RNQR-260103
SELECT-BEYOND
Adults with moderately to severely active RA who had an inadequate response or intolerance to bDMARDs1
RINVOQ is indicated for TNFi-IR patients1
Upadacitinib 30 mg is not an approved dose.
aStarting at Week 24, initiation of or change in corticosteroids, NSAIDs, acetaminophen, and csDMARDs was permitted. Patients not achieving response criteria ≥20% improvement in SJC and TJC at 2 consecutive visits were removed from the study.4,5
bFollowing a protocol amendment, all patients in the long-term extension received UPA 15 mg QD, including those previously on UPA 30 mg.8
PRIMARY ENDPOINT1
RANKED SECONDARY ENDPOINTS6,7
At Week 12:
SELECT PRESPECIFIED NONRANKED ENDPOINTS7
DATA LIMITATIONS
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
BASELINE CHARACTERISTICS6
| MEAN (SD) OR N (%) | PBO + csDMARDs n=169 | RINVOQ 15 mg + csDMARDs n=164 |
|---|---|---|
| Female, n (%) | 143 (85) | 137 (84) |
| Age (years), mean (SD) | 57.6 (11.4) | 56.3 (11.3) |
| Duration since RA diagnosis (years), mean (SD) | 14.5 (9.2) | 12.4 (9.4) |
| RF+ and/or ACPA+, n (%) | 128 (76) | 131 (80) |
| csDMARD use at baseline* | ||
| - MTX alone,† n (%) | 122 (73) | 118 (73) |
| - MTX plus other csDMARD,‡ n (%) | 17 (10) | 19 (12) |
| - MTX dose§ (mg), mean (SD) | 16.6 (4.7) | 17.3 (4.6) |
| - csDMARD other than MTX, n (%) | 29 (17) | 24 (15) |
| - Missing, n | 1 | 3 |
| Prior bDMARD exposure | ||
| - 1, n (%) | 83 (49) | 86 (52) |
| - 2, n (%) | 46 (27) | 40 (24) |
| - ≥3, n (%) | 40 (24) | 38 (23) |
| Inadequate response or intolerance to ≥1 anti-TNF drug | 152 (90) | 146 (89) |
| - Lack of efficacy with ≥1 bDMARD | 159 (94) | 146 (89) |
| - Lack of efficacy with ≥1 anti–IL-6 | 30 (18) | 27 (16) |
| Oral glucocorticoid use, n (%) | 74 (44) | 83 (51) |
| - Oral glucocorticoid dosell (mg), mean (SD) | 6.3 (2.4) | 5.7 (2.4) |
| TJC68, mean (SD) | 28.5 (15.3) | 27.8 (16.3) |
| SJC66, mean (SD) | 16.3 (9.6) | 17.0 (10.8) |
| PtGA (0–100 mm VAS), mean (SD) | 66.3 (22.7) | 67.2 (19.6) |
| PhGA (0–100 mm VAS), mean (SD) | 66.9 (16.9) | 68.7 (16.6) |
| Pain (0–100 mm VAS), mean (SD) | 68.9 (21.0) | 68.2 (19.8) |
| hsCRP (mg/L), mean (SD) | 16.3 (21.1) | 16.2 (18.6) |
| DAS28-CRP, mean (SD) | 5.8 (1.0) | 5.9 (1.0) |
| HAQ-DI, mean (SD) | 1.6 (0.6) | 1.7 (0.6) |
| CDAI, mean (SD) | 41.0 (13.3) | 41.7 (13.3) |
| SDAI, mean (SD) | 42.6 (13.9) | 43.3 (13.8) |
*Oral or parenteral methotrexate (7.5–25 mg per week).
†Data available for 168 patients receiving placebo and 161 patients receiving RINVOQ 15 mg.
‡All combinations allowed except MTX and leflunomide.
§Mean MTX dose calculated only for patients receiving MTX.
‖Based on prednisone equivalent.
ACPA=anti‑citrullinated protein antibodies; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; bDMARD=biologic disease‑modifying antirheumatic drug; CDAI=Clinical Disease Activity Index; CR=clinical remission; CRP=C‑reactive protein; csDMARD=conventional synthetic disease‑modifying antirheumatic drug; DAS28-CRP=28-joint disease activity score using C-reactive protein; DAS28-ESR=28-joint disease activity score using erythrocyte sedimentation rate; ESR=erythrocyte sedimentation rate; HAQ‑DI=Health Assessment Questionnaire Disability Index; hsCRP=high‑sensitivity C‑reactive protein; IL-6=interleukin 6; IR=intolerance or inadequate response; LDA=low disease activity; MTX=methotrexate; NSAID=nonsteroidal anti‑inflammatory drug; PBO=placebo; PhGA=Physician’s Global Assessment; PtGA=patient global assessment; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=Simplified Disease Activity Index; SF‑36 (PCS)=36‑item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; UPA=upadacitinib; VAS=visual analog scale.
REFERENCES:
SELECT-COMPARE
Adults with moderately to severely active RA who had an inadequate response to MTX1
RINVOQ is indicated for TNFi-IR patients1
aX-ray imaging was performed at these time points; Week 14 for nonresponder patients, who were rescued.2,3
bRescue criteria: At Weeks 14, 18, and 22, if <20% improvement in TJC and SJC vs baseline; at Week 26, all remaining PBO patients were switched to RINVOQ, and patients receiving RINVOQ or active comparator were switched to active comparator or RINVOQ, respectively, if CDAI >10.2
cStarting at Week 26, initiation or change in background RA medication(s), including corticosteroids, NSAIDs, or acetaminophen was permitted.4
dStarting at Week 48, patients who failed to show ≥20% improvement in TJC and SJC compared to baseline at 2 consecutive visits were removed from the study.5
eAt Week 48, initiation or change in csDMARDs was allowed; however, not all patients received background MTX.5
fPatients continued treatment with UPA or active comparator in a blinded manner until the last patient completed the Week 48 visit and received open-label treatment thereafter.8
PRIMARY ENDPOINT1
SELECT RANKED SECONDARY ENDPOINTS2
At Week 12 vs placebo + MTX:
At Week 12 vs active comparator + MTX:
At Week 26 vs placebo + MTX:
SELECT PRESPECIFIED NONRANKED ENDPOINTS3,9,10
DATA LIMITATIONS
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
SELECT-COMPARE was not designed to evaluate the efficacy of active comparator + MTX vs placebo + MTX. No conclusions regarding this comparison can be made.
BASELINE CHARACTERISTICS3
| MEAN (SD) OR N (%) | PBO + MTX n=651 | RINVOQ 15 mg QD + MTX n=651 |
|---|---|---|
| Female, n (%) | 512 (79) | 521 (80) |
| Age (years), mean (SD) | 54 (12) | 54 (12) |
| Duration since RA diagnosis (years), mean (SD) | 8 (8) | 8 (8) |
| RF+ and/or anti-CCP+, n (%) | 571 (88) | 566 (87) |
| MTX dose (mg/week), mean (SD) | 16.8 (3.8) | 17.0 (4.2) |
| Prior bDMARD use, n (%) | 63 (10) | 54 (8) |
| Oral glucocorticoid use, n (%) | 392 (60) | 388 (60) |
| - Dose (mg),* mean (SD) | 6.3 (2.4) | 6.2 (2.3) |
| TJC68, mean (SD) | 26 (14) | 26 (15) |
| SJC66, mean (SD) | 16 (9) | 17 (10) |
| PtGA (0–100 mm VAS), mean (SD) | 64 (21) | 64 (22) |
| PhGA (0–100 mm VAS), mean (SD) | 66 (18) | 66 (17) |
| Pain (0–100 mm VAS), mean (SD) | 65 (21) | 66 (21) |
| hsCRP (mg/L), mean (SD) | 18 (22) | 18 (22) |
| DAS28-CRP, mean (SD) | 5.8 (0.9) | 5.8 (1.0) |
| HAQ-DI, mean (SD) | 1.6 (0.6) | 1.6 (0.6) |
| CDAI, mean (SD) | 40 (13) | 40 (13) |
| SDAI, mean (SD) | 41.8 (13.3) | 41.5 (13.6) |
| mTSS, mean (SD) | 36 (52) | 34 (50) |
| - JE score, mean (SD) | 17 (27) | 17 (26) |
| - JSN score, mean (SD) | 19 (26) | 18 (25) |
*Based on prednisone equivalent.
ACPA=anti-citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; bDMARD=biologic disease‑modifying antirheumatic drug; CCP=cyclic citrullinated peptide; CDAI=Clinical Disease Activity Index; CR=clinical remission; CRP=C‑reactive protein; csDMARD=conventional synthetic disease-modifying antirheumatic drug; DAS28-CRP=28-joint disease activity score using C-reactive protein; DAS28-ESR=28-joint disease activity score using erythrocyte sedimentation rate; EOW=every other week; ESR=erythrocyte sedimentation rate; HAQ‑DI=Health Assessment Questionnaire Disability Index; hsCRP=high-sensitivity C‑reactive protein; IR=intolerance or inadequate response; JE=joint erosion; JSN=joint space narrowing; LDA=low disease activity; mTSS=modified total Sharp score; MTX=methotrexate; NSAID=nonsteroidal anti-inflammatory drug; PBO=placebo; PhGA=Physician's Global Assessment; PtGA=patient global assessment; QD=once per day; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=Simplified Disease Activity Index; SF‑36 (PCS)=36-item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; UPA=upadacitinib; VAS=visual analog scale.
REFERENCES:
SELECT-MONOTHERAPY
Adults with moderately to severely active RA who had an inadequate response to MTX1
RINVOQ is indicated for TNFi-IR patients1
Upadacitinib 30 mg is not an approved dose.
aPatients on cMTX were randomized to receive either RINVOQ 15 mg or upadacitinib 30 mg at Week 14.3
bStarting at Week 26, patients who did not achieve CDAI ≤10 could have initiated or adjusted corticosteroids, NSAIDs, acetaminophen, or ≤2 csDMARDs. Patients who failed to show ≥20% improvement in TJC and SJC compared to baseline at 2 consecutive visits were removed from the study.5
cFollowing a protocol amendment, all patients in the long-term extension received UPA 15 mg QD, including those previously on UPA 30 mg.4
PRIMARY ENDPOINT1
RANKED SECONDARY ENDPOINTS3,6
At Week 14:
SELECT PRESPECIFIED NONRANKED ENDPOINTS3,6
DATA LIMITATIONS
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
BASELINE CHARACTERISTICS3
| MEAN (SD) OR N (%) | cMTX n=216 | RINVOQ 15 mg QD n=217 |
|---|---|---|
| Female, n (%) | 179 (83) | 174 (80) |
| Age (years), mean (SD) | 55.3 (11.1) | 54.5 (12.2) |
| Duration since RA diagnosis (years), mean (SD) | 5.8 (6.6) | 7.5 (8.9) |
| RF+ and/or ACPA+, n (%) | 169 (78) | 172 (79) |
| Prior MTX dose* (mg/week), mean (SD) | 16.7 (4.4) | 16.8 (4.2) |
| Prior MTX duration (years), mean (SD) | 3.3 (3.9) | 3.8 (4.8) |
| Oral glucocorticoid use, n (%) | 115 (53) | 114 (53) |
| - Oral glucocorticoid dose† (mg), mean (SD) | 6.2 (2.6) | 6.1 (2.5) |
| TJC68, mean (SD) | 25.2 (16.0) | 24.5 (15.1) |
| SJC66, mean (SD) | 16.9 (11.5) | 16.4 (10.9) |
| PtGA (0–100 mm VAS), mean (SD) | 59.6 (21.8) | 62.2 (22.3) |
| PhGA (0–100 mm VAS), mean (SD) | 62.1 (17.5) | 65.7 (18.5) |
| Pain (0–100 mm VAS), mean (SD) | 62.5 (21.3) | 62.3 (22.5) |
| hsCRP (mg/L), mean (SD) | 14.5 (17.3) | 14.0 (16.5) |
| DAS28-CRP, mean (SD) | 5.6 (1.0) | 5.6 (0.9) |
| HAQ-DI, mean (SD) | 1.5 (0.7) | 1.5 (0.7) |
| CDAI, mean (SD) | 37.8 (14.4) | 38.0 (13.1) |
| SDAI, mean (SD) | 39.2 (14.6) | 39.4 (13.4) |
*Prior to receiving study drug. In the control arm, patients continued prior MTX dose as blinded study drug.3
†Prednisone equivalent.
ACPA=anti‑citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; CDAI=Clinical Disease Activity Index; cMTX=continuous methotrexate; csDMARD=conventional synthetic disease‑modifying antirheumatic drug; CR=clinical remission; CRP=C‑reactive protein; DAS28-CRP=28-joint disease activity score using C-reactive protein; DAS28-ESR=28-joint disease activity score using erythrocyte sedimentation rate; ESR=erythrocyte sedimentation rate; HAQ‑DI=Health Assessment Questionnaire Disability Index; hsCRP=high-sensitivity C‑reactive protein; IR=intolerance or inadequate response; LDA=low disease activity; MTX=methotrexate; NSAID=nonsteroidal anti‑inflammatory drug; PhGA=Physician’s Global Assessment; PtGA=patient global assessment; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=Simplified Disease Activity Index; SF‑36 (PCS)=36-item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; UPA=upadacitinib; VAS=visual analog scale.
REFERENCES:
SELECT-SWITCH
Head-to-head study powered to evaluate superiority of RINVOQ vs HUMIRA (adalimumab) in RA patients who had inadequate response or intolerance to 1 TNFi2
A 12-week, randomized, double-blind, active-comparator–controlled study of 491 adult patients with moderate to severe RA who did not respond to 1 TNFi (non-adalimumab). Designed to evaluate superiority of continuing TNFi therapy with HUMIRA (adalimumab) vs switching to RINVOQ (upadacitinib).
PRIMARY ENDPOINT2
SELECT RANKED SECONDARY ENDPOINTS2
At Week 12 vs HUMIRA:
SELECT PRESPECIFIED NONRANKED ENDPOINTS2
At all visits:
| MEAN (SD) Unless otherwise stated |
RINVOQ 15 mg QD + MTX (n=245) | HUMIRA 40 mg EOW + MTX n=246* |
|---|---|---|
| Parameter | ||
| Age (years) | 55.3 (12.7) | 55.9 (12.5) |
| Age ≥65 years, n (%) | 57 (23.3) | 72 (29.3) |
| Female, n (%) | 189 (77.1) | 191 (77.6) |
| BMI (kg/m2) | 29.4 (6.5) | 28.8 (7.0) |
| RA duration since diagnosis (years) | 10.1 (8.5) (n=244) | 10.3 (9.3) |
| Disease Characteristics | ||
| DAS28-CRP | 5.7 (0.8) (n=235) | 5.7 (0.8) (n=236) |
| DAS28-ESR | 6.3 (0.9) (n=234) | 6.4 (0.9) (n=235) |
| TJC68 | 22.4 (12.3) | 22.8 (12.6) |
| SJC66 | 15.5 (6.6) | 15.9 (8.3) |
| hsCRP (mg/L) | 16.8 (25.4) (n=245) | 14.0 (17.6) |
| ESR (mm/hr) | 37.1 (23.4) (n=243) | 38.9 (24.4) (n=245) |
| PtGA (0–10 NRS) | 7.1 (1.9) (n=235) | 7.4 (1.9) (n=236) |
| PhGA (0–10 NRS) | 7.0 (1.6) | 6.9 (1.6) |
| Pain (0–10 NRS) | 7.4 (1.9) | 7.4 (1.9) (n=232) |
| HAQ-DI | 1.6 (0.6) (n=234) | 1.6 (0.6) (n=234) |
| FACIT-Fatigue | 26.8 (11.5) (n=234) | 26.8 (10.5) (n=233) |
| Concomitant Therapies | ||
| Patients receiving oral corticosteroid at baseline, n (%) | 99 (40.4) | 100 (40.7) |
| Oral steroid dose (prednisone equivalent) at baseline (mg/day) | 6.4 (2.7) (n=99) | 6.7 (3.2) (n=100) |
| MTX dose at baseline (mg/week), median | 15.0 | 15.0 (n=245) |
| NSAIDs | 128 (52.2) | 111 (45.1) |
| Patient History, n (%) | ||
| HZ vaccination | 35 (14.6) | 31 (12.8) |
| History of VTE | 2 (0.8) | 2 (0.8) |
| History of CV event | 18 (7.3) | 11 (4.5) |
| Number of CV risk factorsa, n (%) | ||
| 0 | 72 (29.4) | 65 (26.4) |
| 1 | 94 (38.4) | 107 (43.5) |
| 2 | 58 (23.7) | 61 (24.8) |
| 3+ | 21 (8.6) | 13 (5.3) |
| CV risk factors at baseline, n (%) | ||
| Hypertension | 90 (36.7) | 85 (34.6) |
| Diabetes mellitus | 6 (2.4) | 2 (0.8) |
| History of tobacco/nicotine use (current/former) | 89 (36.3) | 77 (31.3) |
| Elevated LDL-Cb | 42 (17.1) | 65 (26.4) |
| Low HDL-Cc | 36 (14.7) | 32 (13.0) |
| Reason for discontinuation of prior TNFi, n (%) | ||
| Intolerance | 25 (10.2) | 27 (11.0) |
| Inadequate response | 220 (89.8) | 219 (89.0) |
| Type of inadequate response to prior TNFi, n (%) | ||
| Primary nonresponder | 121 (55.8) | 115 (54.0) |
| Secondary nonresponder | 96 (44.2) | 98 (46.0) |
| Missing | 3 | 6 |
| Prior TNFi administered, n (%) | ||
| Etanercept | 165 (67.3) | 170 (69.1) |
| Certolizumab | 40 (16.3) | 35 (14.2) |
| Golimumab | 24 (9.8) | 21 (8.5) |
| Infliximab | 15 (6.1) | 13 (5.3) |
| Adalimumab† | 0 | 1 (0.4) |
*Patients entered the study while receiving a stable dose of MTX (15–25 mg/week). MTX was not considered an ancillary drug in the study.2
†Protocol deviations.2
aCV risk factors included CV event, hypertension, diabetes mellitus, tobacco/nicotine use, elevated LDL-C, and lowered HDL‑C.
b≥3.36 mmol/L (ie, >129.9 mg/dL).
c<1.034 mmol/L (ie, <18.6 mg/dL).
ACR=American College of Rheumatology; BMI=body mass index; CDAI=Clinical Disease Activity Index; CRP=C-reactive protein; CV=cardiovascular; DAS28-CRP=Disease Activity Score in 28 joints using C-reactive protein; DAS28-ESR=28-joint Disease Activity Score using erythrocyte sedimentation rate; EOW=every other week; ESR=erythrocyte sedimentation rate; FACIT-Fatigue=Functional Assessment of Chronic Illness Therapy-Fatigue; HAQ-DI=Health Assessment Questionnaire-Disability Index; HDL-C=high-density lipoprotein cholesterol; hsCRP=high-sensitivity C-reactive protein; HZ=herpes zoster; IR=intolerance or inadequate response; LDA=low disease activity; LDL-C=low-density lipoprotein cholesterol; MACE=major adverse cardiovascular event; MTX=methotrexate; NSAID=nonsteroidal anti-inflammatory drug; PhGA=Physician's Global Assessment; PtGA=patient global assessment; primary nonresponder=patient who did not respond to prior TNFi treatment; QD=once daily; RA=rheumatoid arthritis; SC=subcutaneous; SD=standard deviation; SDAI=Simplified Disease Activity Index; secondary nonresponder=patient who initially responded to prior TNFi treatment but lost response over time; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; VTE=venous thromboembolism.
REFERENCES:
SELECT-EARLY
Adults with moderately to severely active RA who were MTX‑naïve1
RINVOQ is indicated for TNFi-IR patients1
Upadacitinib 30 mg is not an approved dose.
aInitially 947 patients were randomized in the study, but 2 patients were never dosed.
bX-ray images of hands and feet obtained at these time points.2
cStarting at Week 12, patients with ≤20% improvement in TJC and SJC compared to baseline at 2 consecutive visits continued blinded therapy and optimized background RA medications (corticosteroids, NSAIDs, and/or low‑potency analgesics).3,4
dAt Week 26, patients with CDAI ≤2.8 continued their original study drug; background medications (NSAIDs, corticosteroids, and/or low‑potency analgesics, and csDMARDs) were optimized in patients with CDAI >2.8 but ≥20% improvement in TJC and SJC; among patients with CDAI >2.8 and <20% improvement in TJC and SJC, RINVOQ 15 mg or upadacitinib 30 mg were added by re‑randomization according to 1:1 ratio for those initially randomized to MTX, and MTX was added for those initially randomized to RINVOQ 15 mg or upadacitinib 30 mg.2,5
eStarting at Week 48, patients who did not achieve ≥20% improvement in both TJC and SJC at 2 consecutive visits were removed from the study. Initiation of or change in background RA medications (NSAIDs, corticosteroids, low-potency analgesics, and csDMARDs; not all patients received background MTX) is allowed at anytime during Period 2.6
fFollowing a protocol amendment, all patients in the long-term extension who were previously receiving UPA 30 mg received RINVOQ 15 mg.11
PRIMARY ENDPOINT1
RANKED SECONDARY ENDPOINTS3,8
At Week 12:
At Week 24:
SELECT PRESPECIFIED NONRANKED ENDPOINTS2,3,9,10
DATA LIMITATIONS
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
BASELINE CHARACTERISTICS3
| MEAN (SD) OR N (%) | MTX n=314 | RINVOQ 15 mg QD n=317 |
|---|---|---|
| Female, n (%) | 240 (76) | 241 (76) |
| Age (years), mean (SD) | 53.3 (12.9) | 51.9 (12.6) |
| Duration since RA diagnosis (years), mean (SD) | 2.6 (5.1) | 2.9 (5.4) |
| RF+ and/or ACPA+, n (%) | 255 (81) | 279 (88) |
| MTX exposure, n (%) | 19 (6) | 30 (9.5) |
| csDMARD exposure, n (%) | 79 (25) | 80 (25) |
| Oral glucocorticoid use, n (%) | 163 (52) | 147 (46) |
| - Dose (mg),* mean (SD) | 6.4 (2.4) | 6.4 (3.1) |
| TJC68, mean (SD) | 26.4 (16.2) | 25.4 (14.4) |
| SJC66, mean (SD) | 16.9 (10.6) | 16.9 (10.4) |
| PtGA (0–100 mm VAS), mean (SD) | 65.8 (21.5) | 66.6 (22.0) |
| PhGA (0–100 mm VAS), mean (SD) | 68.7 (16.5) | 67.1 (17.0) |
| Pain (0–100 mm VAS), mean (SD) | 65.7 (21.5) | 68.4 (20.6) |
| hsCRP (mg/L), mean (SD) | 21.2 (22.1) | 23.0 (27.4) |
| DAS28-CRP, mean (SD) | 5.9 (1.0) | 5.9 (1.0) |
| HAQ-DI, mean (SD) | 1.6 (0.7) | 1.6 (0.7) |
| CDAI, mean (SD) | 40.5 (13.3) | 40.4 (13.3) |
| SDAI, mean (SD) | 42.6 (14.0) | 42.7 (13.9) |
| mTSS, mean (SD) | 13.3 (30.6) | 18.1 (38.2) |
| - Erosion Score, mean (SD) | 6.1 (15.5) | 8.6 (19.3) |
| - Joint Space Narrowing Score, mean (SD) | 7.2 (16.2) | 9.6 (20.1) |
*Prednisone equivalent dose in patients receiving oral glucocorticoids at baseline.
ACPA=anti-citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; CDAI=Clinical Disease Activity Index; CR=clinical remission; CRP=C-reactive protein; csDMARD=conventional synthetic disease-modifying antirheumatic drug; DAS28-CRP=28-joint disease activity score using C-reactive protein; HAQ-DI=Health Assessment Questionnaire Disability Index; hsCRP=high-sensitivity C-reactive protein; IR=intolerance or inadequate response; JE=joint erosion; JSN=joint space narrowing; LDA=low disease activity; mTSS=modified total Sharp score; MTX=methotrexate; NSAID=nonsteroidal anti-inflammatory drug; PhGA=Physician's Global Assessment; PtGA=patient global assessment; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=Simplified Disease Activity Index; SF-36 (PCS)=36-item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; UPA=upadacitinib; VAS=visual analog scale.
REFERENCES:
SELECT-NEXT
Adults with moderately to severely active RA who had an inadequate response to csDMARD(s)1
RINVOQ is indicated for TNFi-IR patients1
Upadacitinib 30 mg is not an approved dose.
aStarting at Week 24, patients who did not achieve CDAI ≤10 could have initiated or adjusted corticosteroids, NSAIDs, acetaminophen, or ≤2 csDMARDs. Patients who failed to show ≥20% improvement in TJC and SJC compared to baseline at 2 consecutive visits were removed from the study.4
bFollowing a protocol amendment, all patients in the long-term extension received UPA 15 mg QD, including those previously on UPA 30 mg.7
PRIMARY ENDPOINT1
RANKED SECONDARY ENDPOINTS5,6
At Week 12:
SELECT PRESPECIFIED NONRANKED ENDPOINTS6
DATA LIMITATIONS
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
BASELINE CHARACTERISTICS3
| MEAN (SD) OR N (%) | PBO + csDMARDs n=221 | RINVOQ 15 mg QD + csDMARDs n=221 |
|---|---|---|
| Female, n (%) | 166 (75) | 182 (82) |
| Age (years), mean (SD) | 56.0 (12.2) | 55.3 (11.5) |
| Duration since RA diagnosis (years), mean (SD) | 7.2 (7.5) | 7.3 (7.9) |
| RF+ and/or ACPA+, n (%) | 181 (82) | 184 (83) |
| csDMARD use at baseline | ||
| - MTX alone, n (%) | 141 (64) | 122 (55) |
| - MTX plus other csDMARD, n (%) | 49 (22) | 47 (21) |
| - csDMARD other than MTX, n (%) | 30 (14) | 51 (23) |
| - Missing, n (%) | 1 (<1) | 1 (<1) |
| Prior bDMARD exposure, n (%) | 29 (13) | 27 (12) |
| Oral glucocorticoid use, n (%) | 106 (48) | 96 (43) |
| - Oral glucocorticoid dose* (mg), mean (SD) | 6.3 (2.6) | 6.0 (2.4) |
| TJC68, mean (SD) | 24.7 (15.0) | 25.2 (13.8) |
| SJC66, mean (SD) | 15.4 (9.2) | 16.0 (10.0) |
| PtGA (0–100 mm VAS), mean (SD) | 60.3 (20.5) | 63.1 (21.9) |
| PhGA (0–100 mm VAS), mean (SD) | 64.4 (17.7) | 64.3 (16.2) |
| Pain (0–100 mm VAS), mean (SD) | 61.5 (20.8) | 64.1 (19.5) |
| hsCRP (mg/L), mean (SD) | 12.6 (14.0) | 16.6 (19.2) |
| DAS28-CRP, mean (SD) | 5.6 (0.8) | 5.7 (1.0) |
| HAQ-DI, mean (SD) | 1.4 (0.6) | 1.5 (0.6) |
| CDAI, mean (SD) | 37.8 (11.8) | 38.3 (11.9) |
| SDAI, mean (SD) | 39.0 (11.9) | 39.9 (12.5) |
*Based on prednisone equivalent.
ACPA=anti-citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; bDMARD=biologic disease-modifying antirheumatic drug; CDAI=Clinical Disease Activity Index; CR=clinical remission; CRP=C-reactive protein; csDMARD=conventional synthetic disease-modifying antirheumatic drug; DAS28-CRP=28-joint disease activity score using C-reactive protein; HAQ-DI=Health Assessment Questionnaire Disability Index; hsCRP=high-sensitivity C-reactive protein; IR=intolerance or inadequate response; JE=joint erosion; JSN=joint space narrowing; LDA=low disease activity; MTX=methotrexate; NSAID=nonsteroidal anti-inflammatory drug; PBO=placebo; PhGA=Physician's Global Assessment; PtGA=patient global assessment; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=Simplified Disease Activity Index; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; UPA=upadacitinib; VAS=visual analog scale.
REFERENCES:
US-RNQR-260103
SELECT-BEYOND
Adults with moderately to severely active RA who had an inadequate response or intolerance to bDMARDs1
RINVOQ is indicated for TNFi-IR patients1
Upadacitinib 30 mg is not an approved dose.
aStarting at Week 24, initiation of or change in corticosteroids, NSAIDs, acetaminophen, and csDMARDs was permitted. Patients not achieving response criteria ≥20% improvement in SJC and TJC at 2 consecutive visits were removed from the study.4,5
bFollowing a protocol amendment, all patients in the long-term extension received UPA 15 mg QD, including those previously on UPA 30 mg.8
PRIMARY ENDPOINT1
RANKED SECONDARY ENDPOINTS6,7
At Week 12:
SELECT PRESPECIFIED NON-RANKED ENDPOINTS7
DATA LIMITATIONS
Prespecified non-ranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
BASELINE CHARACTERISTICS6
| MEAN (SD) OR N (%) | PBO + csDMARDs n=169 | RINVOQ 15 mg + csDMARDs n=164 |
|---|---|---|
| Female, n (%) | 143 (85) | 137 (84) |
| Age (years), mean (SD) | 57.6 (11.4) | 56.3 (11.3) |
| Duration since RA diagnosis (years), mean (SD) | 14.5 (9.2) | 12.4 (9.4) |
| RF+ and/or ACPA+, n (%) | 128 (76) | 131 (80) |
| csDMARD use at baseline* | ||
| - MTX alone,† n (%) | 122 (73) | 118 (73) |
| - MTX plus other csDMARD,‡ n (%) | 17 (10) | 19 (12) |
| - MTX dose§ (mg), mean (SD) | 16.6 (4.7) | 17.3 (4.6) |
| - csDMARD other than MTX, n (%) | 29 (17) | 24 (15) |
| - Missing, n | 1 | 3 |
| Prior bDMARD exposure | ||
| - 1, n (%) | 83 (49) | 86 (52) |
| - 2, n (%) | 46 (27) | 40 (24) |
| - ≥3, n (%) | 40 (24) | 38 (23) |
| Inadequate response or intolerance to ≥1 anti-TNF drug | 152 (90) | 146 (89) |
| - Lack of efficacy with ≥1 bDMARD | 159 (94) | 146 (89) |
| - Lack of efficacy with ≥1 anti-IL-6 | 30 (18) | 27 (16) |
| Oral glucocorticoid use, n (%) | 74 (44) | 83 (51) |
| - Oral glucocorticoid dosell (mg), mean (SD) | 6.3 (2.4) | 5.7 (2.4) |
| TJC68, mean (SD) | 28.5 (15.3) | 27.8 (16.3) |
| SJC66, mean (SD) | 16.3 (9.6) | 17.0 (10.8) |
| PtGA (0-100 mm VAS), mean (SD) | 66.3 (22.7) | 67.2 (19.6) |
| PhGA (0-100 mm VAS), mean (SD) | 66.9 (16.9) | 68.7 (16.6) |
| Pain (0-100 mm VAS), mean (SD) | 68.9 (21.0) | 68.2 (19.8) |
| hsCRP (mg/L), mean (SD) | 16.3 (21.1) | 16.2 (18.6) |
| DAS28-CRP, mean (SD) | 5.8 (1.0) | 5.9 (1.0) |
| HAQ-DI, mean (SD) | 1.6 (0.6) | 1.7 (0.6) |
| CDAI, mean (SD) | 41.0 (13.3) | 41.7 (13.3) |
| SDAI, mean (SD) | 42.6 (13.9) | 43.3 (13.8) |
*Oral or parenteral methotrexate (7.5-25 mg per week).
†Data available for 168 patients receiving placebo and 161 patients receiving RINVOQ 15 mg.
‡All combinations allowed except MTX and leflunomide.
§Mean MTX dose calculated only for patients receiving MTX.
‖Based on prednisone equivalent.
ACPA=anti‑citrullinated protein antibodies; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; bDMARD=biologic disease‑modifying antirheumatic drug; CDAI=Clinical Disease Activity Index; CR=clinical remission; CRP=C‑reactive protein; csDMARD=conventional synthetic disease‑modifying antirheumatic drug; DAS28-CRP=28-joint disease activity score using C-reactive protein; DAS28-ESR=28-joint disease activity score using erythrocyte sedimentation rate; ESR=erythrocyte sedimentation rate; HAQ‑DI=Health Assessment Questionnaire Disability Index; hsCRP=high‑sensitivity C‑reactive protein; IL-6=interleukin 6; IR=intolerance or inadequate response; LDA=low disease activity; MTX=methotrexate; NSAID=nonsteroidal anti‑inflammatory drug; PBO=placebo; PhGA=physician’s global assessment of disease activity; PtGA=patient’s global assessment of disease activity; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=Simplified Disease Activity Index; SF‑36 (PCS)=36‑item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; UPA=upadacitinib; VAS=visual analog scale.
REFERENCES:
SELECT-EARLY
Adults with moderately to severely active RA who were MTX‑naïve1
RINVOQ is indicated for TNFi-IR patients1
Upadacitinib 30 mg is not an approved dose.
aInitially 947 patients were randomized in the study, but 2 patients were never dosed.
bX-ray images of hands and feet obtained at these time points.2
cStarting at Week 12, patients with ≤20% improvement in TJC and SJC compared to baseline at 2 consecutive visits continued blinded therapy and optimized background RA medications (corticosteroids, NSAIDs, and/or low‑potency analgesics).3,4
dAt Week 26, patients with CDAI ≤2.8 continued their original study drug; background medications (NSAIDs, corticosteroids, and/or low‑potency analgesics, and csDMARDs) were optimized in patients with CDAI >2.8 but ≥20% improvement in TJC and SJC; among patients with CDAI >2.8 and <20% improvement in TJC and SJC, RINVOQ 15 mg or upadacitinib 30 mg were added by re‑randomization according to 1:1 ratio for those initially randomized to MTX, and MTX was added for those initially randomized to RINVOQ 15 mg or upadacitinib 30 mg.2,5
eStarting at Week 48, patients who did not achieve ≥20% improvement in both TJC and SJC at 2 consecutive visits were removed from the study. Initiation of or change in background RA medications (NSAIDs, corticosteroids, low-potency analgesics, and csDMARDs; not all patients received background MTX) is allowed at anytime during Period 2.6
fFollowing a protocol amendment, all patients in the long-term extension who were previously receiving UPA 30 mg received RINVOQ 15 mg.11
PRIMARY ENDPOINT1
RANKED SECONDARY ENDPOINTS3,8
At Week 12:
At Week 24:
SELECT PRESPECIFIED NON-RANKED ENDPOINTS2,3,9,10
DATA LIMITATIONS
Prespecified non-ranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
BASELINE CHARACTERISTICS3
| MEAN (SD) OR N (%) | MTX n=314 | RINVOQ 15 mg QD n=317 |
|---|---|---|
| Female, n (%) | 240 (76) | 241 (76) |
| Age (years), mean (SD) | 53.3 (12.9) | 51.9 (12.6) |
| Duration since RA diagnosis (years), mean (SD) | 2.6 (5.1) | 2.9 (5.4) |
| RF+ and/or ACPA+, n (%) | 255 (81) | 279 (88) |
| MTX exposure, n (%) | 19 (6) | 30 (9.5) |
| csDMARD exposure, n (%) | 79 (25) | 80 (25) |
| Oral glucocorticoid use, n (%) | 163 (52) | 147 (46) |
| - Dose (mg),* mean (SD) | 6.4 (2.4) | 6.4 (3.1) |
| TJC68, mean (SD) | 26.4 (16.2) | 25.4 (14.4) |
| SJC66, mean (SD) | 16.9 (10.6) | 16.9 (10.4) |
| PtGA (0-100 mm VAS), mean (SD) | 65.8 (21.5) | 66.6 (22.0) |
| PhGA (0-100 mm VAS), mean (SD) | 68.7 (16.5) | 67.1 (17.0) |
| Pain (0-100 mm VAS), mean (SD) | 65.7 (21.5) | 68.4 (20.6) |
| hsCRP (mg/L), mean (SD) | 21.2 (22.1) | 23.0 (27.4) |
| DAS28-CRP, mean (SD) | 5.9 (1.0) | 5.9 (1.0) |
| HAQ-DI, mean (SD) | 1.6 (0.7) | 1.6 (0.7) |
| CDAI, mean (SD) | 40.5 (13.3) | 40.4 (13.3) |
| SDAI, mean (SD) | 42.6 (14.0) | 42.7 (13.9) |
| mTSS, mean (SD) | 13.3 (30.6) | 18.1 (38.2) |
| - Erosion Score, mean (SD) | 6.1 (15.5) | 8.6 (19.3) |
| - Joint Space Narrowing Score, mean (SD) | 7.2 (16.2) | 9.6 (20.1) |
*Prednisone equivalent dose in patients receiving oral glucocorticoids at baseline.
ACPA=anti-citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; CDAI=Clinical Disease Activity Index; CR=clinical remission; CRP=C-reactive protein; csDMARD=conventional synthetic disease-modifying antirheumatic drug; DAS28-CRP=28-joint disease activity score using C-reactive protein; HAQ-DI=Health Assessment Questionnaire Disability Index; hsCRP=high-sensitivity C-reactive protein; IR=intolerance or inadequate response; JE=joint erosion; JSN=joint space narrowing; LDA=low disease activity; mTSS=modified total Sharp score; MTX=methotrexate; NSAID=nonsteroidal anti-inflammatory drug; PhGA=physician’s global assessment of disease activity; PtGA=patient’s global assessment of disease activity; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=Simplified Disease Activity Index; SF-36 (PCS)=36-item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; UPA=upadacitinib; VAS=visual analog scale.
REFERENCES:
SELECT-MONOTHERAPY
Adults with moderately to severely active RA who had an inadequate response to MTX1
RINVOQ is indicated for TNFi-IR patients1
Upadacitinib 30 mg is not an approved dose.
aPatients on cMTX were randomized to receive either RINVOQ 15 mg or upadacitinib 30 mg at Week 14.3
bStarting at Week 26, patients who did not achieve CDAI ≤10 could have initiated or adjusted corticosteroids, NSAIDs, acetaminophen, or ≤2 csDMARDs. Patients who failed to show ≥20% improvement in TJC and SJC compared to baseline at 2 consecutive visits were removed from the study.5
cFollowing a protocol amendment, all patients in the long-term extension received UPA 15 mg QD, including those previously on UPA 30 mg.4
PRIMARY ENDPOINT1
RANKED SECONDARY ENDPOINTS3,6
At Week 14:
SELECT PRESPECIFIED NON-RANKED ENDPOINTS3,6
DATA LIMITATIONS
Prespecified non-ranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
BASELINE CHARACTERISTICS3
| MEAN (SD) OR N (%) | cMTX n=216 | RINVOQ 15 mg QD n=217 |
|---|---|---|
| Female, n (%) | 179 (83) | 174 (80) |
| Age (years), mean (SD) | 55.3 (11.1) | 54.5 (12.2) |
| Duration since RA diagnosis (years), mean (SD) | 5.8 (6.6) | 7.5 (8.9) |
| RF+ and/or ACPA+, n (%) | 169 (78) | 172 (79) |
| Prior MTX dose* (mg/week), mean (SD) | 16.7 (4.4) | 16.8 (4.2) |
| Prior MTX duration (years), mean (SD) | 3.3 (3.9) | 3.8 (4.8) |
| Oral glucocorticoid use, n (%) | 115 (53) | 114 (53) |
| - Oral glucocorticoid dose† (mg), mean (SD) | 6.2 (2.6) | 6.1 (2.5) |
| TJC68, mean (SD) | 25.2 (16.0) | 24.5 (15.1) |
| SJC66, mean (SD) | 16.9 (11.5) | 16.4 (10.9) |
| PtGA (0-100 mm VAS), mean (SD) | 59.6 (21.8) | 62.2 (22.3) |
| PhGA (0-100 mm VAS), mean (SD) | 62.1 (17.5) | 65.7 (18.5) |
| Pain (0-100 mm VAS), mean (SD) | 62.5 (21.3) | 62.3 (22.5) |
| hsCRP (mg/L), mean (SD) | 14.5 (17.3) | 14.0 (16.5) |
| DAS28-CRP, mean (SD) | 5.6 (1.0) | 5.6 (0.9) |
| HAQ-DI, mean (SD) | 1.5 (0.7) | 1.5 (0.7) |
| CDAI, mean (SD) | 37.8 (14.4) | 38.0 (13.1) |
| SDAI, mean (SD) | 39.2 (14.6) | 39.4 (13.4) |
*Prior to receiving study drug. In the control arm, patients continued prior MTX dose as blinded study drug.3
†Prednisone equivalent.
ACPA=anti‑citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; CDAI=Clinical Disease Activity Index; cMTX=continuous methotrexate; csDMARD=conventional synthetic disease‑modifying antirheumatic drug; CR=clinical remission; CRP=C‑reactive protein; DAS28-CRP=28-joint disease activity score using C-reactive protein; DAS28-ESR=28-joint disease activity score using erythrocyte sedimentation rate; ESR=erythrocyte sedimentation rate; HAQ‑DI=Health Assessment Questionnaire Disability Index; hsCRP=high-sensitivity C‑reactive protein; IR=intolerance or inadequate response; LDA=low disease activity; MTX=methotrexate; NSAID=nonsteroidal anti‑inflammatory drug; PhGA=physician’s global assessment of disease activity; PtGA=patient’s global assessment of disease activity; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=Simplified Disease Activity Index; SF‑36 (PCS)=36-item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; UPA=upadacitinib; VAS=visual analog scale.
REFERENCES:
SELECT-NEXT
Adults with moderately to severely active RA who had an inadequate response to csDMARD(s)1
RINVOQ is indicated for TNFi-IR patients1
Upadacitinib 30 mg is not an approved dose.
aStarting at Week 24, patients who did not achieve CDAI ≤10 could have initiated or adjusted corticosteroids, NSAIDs, acetaminophen, or ≤2 csDMARDs. Patients who failed to show ≥20% improvement in TJC and SJC compared to baseline at 2 consecutive visits were removed from the study.4
bFollowing a protocol amendment, all patients in the long-term extension received UPA 15 mg QD, including those previously on UPA 30 mg.7
PRIMARY ENDPOINT1
RANKED SECONDARY ENDPOINTS5,6
At Week 12:
SELECT PRESPECIFIED NON-RANKED ENDPOINTS6
DATA LIMITATIONS
Prespecified non-ranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
BASELINE CHARACTERISTICS3
| MEAN (SD) OR N (%) | PBO + csDMARDs n=221 | RINVOQ 15 mg QD + csDMARDs n=221 |
|---|---|---|
| Female, n (%) | 166 (75) | 182 (82) |
| Age (years), mean (SD) | 56.0 (12.2) | 55.3 (11.5) |
| Duration since RA diagnosis (years), mean (SD) | 7.2 (7.5) | 7.3 (7.9) |
| RF+ and/or ACPA+, n (%) | 181 (82) | 184 (83) |
| csDMARD use at baseline | ||
| - MTX alone, n (%) | 141 (64) | 122 (55) |
| - MTX plus other csDMARD, n (%) | 49 (22) | 47 (21) |
| - csDMARD other than MTX, n (%) | 30 (14) | 51 (23) |
| - Missing, n (%) | 1 (<1) | 1 (<1) |
| Prior bDMARD exposure, n (%) | 29 (13) | 27 (12) |
| Oral glucocorticoid use, n (%) | 106 (48) | 96 (43) |
| - Oral glucocorticoid dose* (mg), mean (SD) | 6.3 (2.6) | 6.0 (2.4) |
| TJC68, mean (SD) | 24.7 (15.0) | 25.2 (13.8) |
| SJC66, mean (SD) | 15.4 (9.2) | 16.0 (10.0) |
| PtGA (0-100 mm VAS), mean (SD) | 60.3 (20.5) | 63.1 (21.9) |
| PhGA (0-100 mm VAS), mean (SD) | 64.4 (17.7) | 64.3 (16.2) |
| Pain (0-100 mm VAS), mean (SD) | 61.5 (20.8) | 64.1 (19.5) |
| hsCRP (mg/L), mean (SD) | 12.6 (14.0) | 16.6 (19.2) |
| DAS28-CRP, mean (SD) | 5.6 (0.8) | 5.7 (1.0) |
| HAQ-DI, mean (SD) | 1.4 (0.6) | 1.5 (0.6) |
| CDAI, mean (SD) | 37.8 (11.8) | 38.3 (11.9) |
| SDAI, mean (SD) | 39.0 (11.9) | 39.9 (12.5) |
*Based on prednisone equivalent.
ACPA=anti-citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; bDMARD=biologic disease-modifying antirheumatic drug; CDAI=Clinical Disease Activity Index; CR=clinical remission; CRP=C-reactive protein; csDMARD=conventional synthetic disease-modifying antirheumatic drug; DAS28-CRP=28-joint disease activity score using C-reactive protein; HAQ-DI=Health Assessment Questionnaire Disability Index; hsCRP=high-sensitivity C-reactive protein; IR=intolerance or inadequate response; JE=joint erosion; JSN=joint space narrowing; LDA=low disease activity; MTX=methotrexate; NSAIDs=nonsteroidal anti-inflammatory drugs; PBO=placebo; PhGA=physician's global assessment of disease activity; PtGA=patient's global assessment of disease activity; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=Simplified Disease Activity Index; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; UPA=upadacitinib; VAS=visual analog scale.
REFERENCES:
SELECT-COMPARE
Adults with moderately to severely active RA who had an inadequate response to MTX1
RINVOQ is indicated for TNFi-IR patients1
aX-ray imaging was performed at these time points; Week 14 for nonresponder patients, who were rescued.2,3
bRescue criteria: At Weeks 14, 18, and 22, if <20% improvement in TJC and SJC vs baseline; at Week 26, all remaining PBO patients were switched to RINVOQ, and patients receiving RINVOQ or active comparator were switched to active comparator or RINVOQ, respectively, if CDAI >10.2
cStarting at Week 26, initiation or change in background RA medication(s), including corticosteroids, NSAIDs, or acetaminophen was permitted.4
dStarting at Week 48, patients who failed to show ≥20% improvement in TJC and SJC compared to baseline at 2 consecutive visits were removed from the study.5
eAt Week 48, initiation or change in csDMARDs was allowed; however, not all patients received background MTX.5
fPatients continued treatment with UPA or active comparator in a blinded manner until the last patient completed the Week 48 visit and received open-label treatment thereafter.8
PRIMARY ENDPOINT1
SELECT RANKED SECONDARY ENDPOINTS2
At Week 12 vs placebo + MTX:
At Week 12 vs active comparator + MTX:
At Week 26 vs placebo + MTX:
SELECT PRESPECIFIED NON-RANKED ENDPOINTS3,9,10
DATA LIMITATIONS
Prespecified non-ranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
SELECT-COMPARE was not designed to evaluate the efficacy of active comparator + MTX vs placebo + MTX. No conclusions regarding this comparison can be made.
BASELINE CHARACTERISTICS3
| MEAN (SD) OR N (%) | PBO + MTX n=651 | RINVOQ 15 mg QD + MTX n=651 |
|---|---|---|
| Female, n (%) | 512 (79) | 521 (80) |
| Age (years), mean (SD) | 54 (12) | 54 (12) |
| Duration since RA diagnosis (years), mean (SD) | 8 (8) | 8 (8) |
| RF+ and/or anti-CCP+, n (%) | 571 (88) | 566 (87) |
| MTX dose (mg/week), mean (SD) | 16.8 (3.8) | 17.0 (4.2) |
| Prior bDMARD use, n (%) | 63 (10) | 54 (8) |
| Oral glucocorticoid use, n (%) | 392 (60) | 388 (60) |
| - Dose (mg),* mean (SD) | 6.3 (2.4) | 6.2 (2.3) |
| TJC68, mean (SD) | 26 (14) | 26 (15) |
| SJC66, mean (SD) | 16 (9) | 17 (10) |
| PtGA (0-100 mm VAS), mean (SD) | 64 (21) | 64 (22) |
| PhGA (0-100 mm VAS), mean (SD) | 66 (18) | 66 (17) |
| Pain (0-100 mm VAS), mean (SD) | 65 (21) | 66 (21) |
| hsCRP (mg/L), mean (SD) | 18 (22) | 18 (22) |
| DAS28-CRP, mean (SD) | 5.8 (0.9) | 5.8 (1.0) |
| HAQ-DI, mean (SD) | 1.6 (0.6) | 1.6 (0.6) |
| CDAI, mean (SD) | 40 (13) | 40 (13) |
| SDAI, mean (SD) | 41.8 (13.3) | 41.5 (13.6) |
| mTSS, mean (SD) | 36 (52) | 34 (50) |
| - JE score, mean (SD) | 17 (27) | 17 (26) |
| - JSN score, mean (SD) | 19 (26) | 18 (25) |
*Based on prednisone equivalent.
ACPA=anti-citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; bDMARD=biologic disease‑modifying antirheumatic drug; CCP=cyclic citrullinated peptide; CDAI=Clinical Disease Activity Index; CR=clinical remission; CRP=C‑reactive protein; csDMARD=conventional synthetic disease-modifying antirheumatic drug; DAS28-CRP=28-joint disease activity score using C-reactive protein; DAS28-ESR=28-joint disease activity score using erythrocyte sedimentation rate; EOW=every other week; ESR=erythrocyte sedimentation rate; HAQ‑DI=Health Assessment Questionnaire Disability Index; hsCRP=high-sensitivity C‑reactive protein; IR=intolerance or inadequate response; JE=joint erosion; JSN=joint space narrowing; LDA=low disease activity; mTSS=modified total Sharp score; MTX=methotrexate; NSAID=nonsteroidal anti-inflammatory drug; PBO=placebo; PhGA=physician’s global assessment of disease activity; PtGA=patient’s global assessment of disease activity; QD=once per day; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=Simplified Disease Activity Index; SF‑36 (PCS)=36-item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; UPA=upadacitinib; VAS=visual analog scale.
REFERENCES:
US-RNQ-230377
SELECT-BEYOND
Adults with moderately to severely active RA who had an inadequate response or intolerance to bDMARDs1
RINVOQ is indicated for TNFi-IR patients1
Upadacitinib 30 mg is not an approved dose.
aStarting at Week 24, initiation of or change in corticosteroids, NSAIDs, acetaminophen, and csDMARDs was permitted. Patients not achieving response criteria ≥20% improvement in SJC and TJC at 2 consecutive visits were removed from the study.4,5
bFollowing a protocol amendment, all patients in the long-term extension received UPA 15 mg QD, including those previously on UPA 30 mg.8
PRIMARY ENDPOINT1
RANKED SECONDARY ENDPOINTS6,7
At Week 12:
SELECT PRESPECIFIED NONRANKED ENDPOINTS7
DATA LIMITATIONS
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
BASELINE CHARACTERISTICS6
| MEAN (SD) OR N (%) | PBO + csDMARDs n=169 | RINVOQ 15 mg + csDMARDs n=164 |
|---|---|---|
| Female, n (%) | 143 (85) | 137 (84) |
| Age (years), mean (SD) | 57.6 (11.4) | 56.3 (11.3) |
| Duration since RA diagnosis (years), mean (SD) | 14.5 (9.2) | 12.4 (9.4) |
| RF+ and/or ACPA+, n (%) | 128 (76) | 131 (80) |
| csDMARD use at baseline* | ||
| - MTX alone,† n (%) | 122 (73) | 118 (73) |
| - MTX plus other csDMARD,‡ n (%) | 17 (10) | 19 (12) |
| - MTX dose§ (mg), mean (SD) | 16.6 (4.7) | 17.3 (4.6) |
| - csDMARD other than MTX, n (%) | 29 (17) | 24 (15) |
| - Missing, n | 1 | 3 |
| Prior bDMARD exposure | ||
| - 1, n (%) | 83 (49) | 86 (52) |
| - 2, n (%) | 46 (27) | 40 (24) |
| - ≥3, n (%) | 40 (24) | 38 (23) |
| Inadequate response or intolerance to ≥1 anti-TNF drug | 152 (90) | 146 (89) |
| - Lack of efficacy with ≥1 bDMARD | 159 (94) | 146 (89) |
| - Lack of efficacy with ≥1 anti–IL-6 | 30 (18) | 27 (16) |
| Oral glucocorticoid use, n (%) | 74 (44) | 83 (51) |
| - Oral glucocorticoid dosell (mg), mean (SD) | 6.3 (2.4) | 5.7 (2.4) |
| TJC68, mean (SD) | 28.5 (15.3) | 27.8 (16.3) |
| SJC66, mean (SD) | 16.3 (9.6) | 17.0 (10.8) |
| PtGA (0–100 mm VAS), mean (SD) | 66.3 (22.7) | 67.2 (19.6) |
| PhGA (0–100 mm VAS), mean (SD) | 66.9 (16.9) | 68.7 (16.6) |
| Pain (0–100 mm VAS), mean (SD) | 68.9 (21.0) | 68.2 (19.8) |
| hsCRP (mg/L), mean (SD) | 16.3 (21.1) | 16.2 (18.6) |
| DAS28-CRP, mean (SD) | 5.8 (1.0) | 5.9 (1.0) |
| HAQ-DI, mean (SD) | 1.6 (0.6) | 1.7 (0.6) |
| CDAI, mean (SD) | 41.0 (13.3) | 41.7 (13.3) |
| SDAI, mean (SD) | 42.6 (13.9) | 43.3 (13.8) |
*Oral or parenteral methotrexate (7.5–25 mg per week).
†Data available for 168 patients receiving placebo and 161 patients receiving RINVOQ 15 mg.
‡All combinations allowed except MTX and leflunomide.
§Mean MTX dose calculated only for patients receiving MTX.
‖Based on prednisone equivalent.
ACPA=anti‑citrullinated protein antibodies; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; bDMARD=biologic disease‑modifying antirheumatic drug; CDAI=Clinical Disease Activity Index; CR=clinical remission; CRP=C‑reactive protein; csDMARD=conventional synthetic disease‑modifying antirheumatic drug; DAS28-CRP=28-joint disease activity score using C-reactive protein; DAS28-ESR=28-joint disease activity score using erythrocyte sedimentation rate; ESR=erythrocyte sedimentation rate; HAQ‑DI=Health Assessment Questionnaire Disability Index; hsCRP=high‑sensitivity C‑reactive protein; IL-6=interleukin 6; IR=intolerance or inadequate response; LDA=low disease activity; MTX=methotrexate; NSAID=nonsteroidal anti‑inflammatory drug; PBO=placebo; PhGA=Physician’s Global Assessment; PtGA=patient global assessment; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=Simplified Disease Activity Index; SF‑36 (PCS)=36‑item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; UPA=upadacitinib; VAS=visual analog scale.
REFERENCES:
SELECT-COMPARE
Adults with moderately to severely active RA who had an inadequate response to MTX1
RINVOQ is indicated for TNFi-IR patients1
aX-ray imaging was performed at these time points; Week 14 for nonresponder patients, who were rescued.2,3
bRescue criteria: At Weeks 14, 18, and 22, if <20% improvement in TJC and SJC vs baseline; at Week 26, all remaining PBO patients were switched to RINVOQ, and patients receiving RINVOQ or active comparator were switched to active comparator or RINVOQ, respectively, if CDAI >10.2
cStarting at Week 26, initiation or change in background RA medication(s), including corticosteroids, NSAIDs, or acetaminophen was permitted.4
dStarting at Week 48, patients who failed to show ≥20% improvement in TJC and SJC compared to baseline at 2 consecutive visits were removed from the study.5
eAt Week 48, initiation or change in csDMARDs was allowed; however, not all patients received background MTX.5
fPatients continued treatment with UPA or active comparator in a blinded manner until the last patient completed the Week 48 visit and received open-label treatment thereafter.8
PRIMARY ENDPOINT1
SELECT RANKED SECONDARY ENDPOINTS2
At Week 12 vs placebo + MTX:
At Week 12 vs active comparator + MTX:
At Week 26 vs placebo + MTX:
SELECT PRESPECIFIED NONRANKED ENDPOINTS3,9,10
DATA LIMITATIONS
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
SELECT-COMPARE was not designed to evaluate the efficacy of active comparator + MTX vs placebo + MTX. No conclusions regarding this comparison can be made.
BASELINE CHARACTERISTICS3
| MEAN (SD) OR N (%) | PBO + MTX n=651 | RINVOQ 15 mg QD + MTX n=651 |
|---|---|---|
| Female, n (%) | 512 (79) | 521 (80) |
| Age (years), mean (SD) | 54 (12) | 54 (12) |
| Duration since RA diagnosis (years), mean (SD) | 8 (8) | 8 (8) |
| RF+ and/or anti-CCP+, n (%) | 571 (88) | 566 (87) |
| MTX dose (mg/week), mean (SD) | 16.8 (3.8) | 17.0 (4.2) |
| Prior bDMARD use, n (%) | 63 (10) | 54 (8) |
| Oral glucocorticoid use, n (%) | 392 (60) | 388 (60) |
| - Dose (mg),* mean (SD) | 6.3 (2.4) | 6.2 (2.3) |
| TJC68, mean (SD) | 26 (14) | 26 (15) |
| SJC66, mean (SD) | 16 (9) | 17 (10) |
| PtGA (0–100 mm VAS), mean (SD) | 64 (21) | 64 (22) |
| PhGA (0–100 mm VAS), mean (SD) | 66 (18) | 66 (17) |
| Pain (0–100 mm VAS), mean (SD) | 65 (21) | 66 (21) |
| hsCRP (mg/L), mean (SD) | 18 (22) | 18 (22) |
| DAS28-CRP, mean (SD) | 5.8 (0.9) | 5.8 (1.0) |
| HAQ-DI, mean (SD) | 1.6 (0.6) | 1.6 (0.6) |
| CDAI, mean (SD) | 40 (13) | 40 (13) |
| SDAI, mean (SD) | 41.8 (13.3) | 41.5 (13.6) |
| mTSS, mean (SD) | 36 (52) | 34 (50) |
| - JE score, mean (SD) | 17 (27) | 17 (26) |
| - JSN score, mean (SD) | 19 (26) | 18 (25) |
*Based on prednisone equivalent.
ACPA=anti-citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; bDMARD=biologic disease‑modifying antirheumatic drug; CCP=cyclic citrullinated peptide; CDAI=Clinical Disease Activity Index; CR=clinical remission; CRP=C‑reactive protein; csDMARD=conventional synthetic disease-modifying antirheumatic drug; DAS28-CRP=28-joint disease activity score using C-reactive protein; DAS28-ESR=28-joint disease activity score using erythrocyte sedimentation rate; EOW=every other week; ESR=erythrocyte sedimentation rate; HAQ‑DI=Health Assessment Questionnaire Disability Index; hsCRP=high-sensitivity C‑reactive protein; IR=intolerance or inadequate response; JE=joint erosion; JSN=joint space narrowing; LDA=low disease activity; mTSS=modified total Sharp score; MTX=methotrexate; NSAID=nonsteroidal anti-inflammatory drug; PBO=placebo; PhGA=Physician's Global Assessment; PtGA=patient global assessment; QD=once per day; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=Simplified Disease Activity Index; SF‑36 (PCS)=36-item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; UPA=upadacitinib; VAS=visual analog scale.
REFERENCES:
SELECT-MONOTHERAPY
Adults with moderately to severely active RA who had an inadequate response to MTX1
RINVOQ is indicated for TNFi-IR patients1
Upadacitinib 30 mg is not an approved dose.
aPatients on cMTX were randomized to receive either RINVOQ 15 mg or upadacitinib 30 mg at Week 14.3
bStarting at Week 26, patients who did not achieve CDAI ≤10 could have initiated or adjusted corticosteroids, NSAIDs, acetaminophen, or ≤2 csDMARDs. Patients who failed to show ≥20% improvement in TJC and SJC compared to baseline at 2 consecutive visits were removed from the study.5
cFollowing a protocol amendment, all patients in the long-term extension received UPA 15 mg QD, including those previously on UPA 30 mg.4
PRIMARY ENDPOINT1
RANKED SECONDARY ENDPOINTS3,6
At Week 14:
SELECT PRESPECIFIED NONRANKED ENDPOINTS3,6
DATA LIMITATIONS
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
BASELINE CHARACTERISTICS3
| MEAN (SD) OR N (%) | cMTX n=216 | RINVOQ 15 mg QD n=217 |
|---|---|---|
| Female, n (%) | 179 (83) | 174 (80) |
| Age (years), mean (SD) | 55.3 (11.1) | 54.5 (12.2) |
| Duration since RA diagnosis (years), mean (SD) | 5.8 (6.6) | 7.5 (8.9) |
| RF+ and/or ACPA+, n (%) | 169 (78) | 172 (79) |
| Prior MTX dose* (mg/week), mean (SD) | 16.7 (4.4) | 16.8 (4.2) |
| Prior MTX duration (years), mean (SD) | 3.3 (3.9) | 3.8 (4.8) |
| Oral glucocorticoid use, n (%) | 115 (53) | 114 (53) |
| - Oral glucocorticoid dose† (mg), mean (SD) | 6.2 (2.6) | 6.1 (2.5) |
| TJC68, mean (SD) | 25.2 (16.0) | 24.5 (15.1) |
| SJC66, mean (SD) | 16.9 (11.5) | 16.4 (10.9) |
| PtGA (0–100 mm VAS), mean (SD) | 59.6 (21.8) | 62.2 (22.3) |
| PhGA (0–100 mm VAS), mean (SD) | 62.1 (17.5) | 65.7 (18.5) |
| Pain (0–100 mm VAS), mean (SD) | 62.5 (21.3) | 62.3 (22.5) |
| hsCRP (mg/L), mean (SD) | 14.5 (17.3) | 14.0 (16.5) |
| DAS28-CRP, mean (SD) | 5.6 (1.0) | 5.6 (0.9) |
| HAQ-DI, mean (SD) | 1.5 (0.7) | 1.5 (0.7) |
| CDAI, mean (SD) | 37.8 (14.4) | 38.0 (13.1) |
| SDAI, mean (SD) | 39.2 (14.6) | 39.4 (13.4) |
*Prior to receiving study drug. In the control arm, patients continued prior MTX dose as blinded study drug.3
†Prednisone equivalent.
ACPA=anti‑citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; CDAI=Clinical Disease Activity Index; cMTX=continuous methotrexate; csDMARD=conventional synthetic disease‑modifying antirheumatic drug; CR=clinical remission; CRP=C‑reactive protein; DAS28-CRP=28-joint disease activity score using C-reactive protein; DAS28-ESR=28-joint disease activity score using erythrocyte sedimentation rate; ESR=erythrocyte sedimentation rate; HAQ‑DI=Health Assessment Questionnaire Disability Index; hsCRP=high-sensitivity C‑reactive protein; IR=intolerance or inadequate response; LDA=low disease activity; MTX=methotrexate; NSAID=nonsteroidal anti‑inflammatory drug; PhGA=Physician’s Global Assessment; PtGA=patient global assessment; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=Simplified Disease Activity Index; SF‑36 (PCS)=36-item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; UPA=upadacitinib; VAS=visual analog scale.
REFERENCES:
SELECT-SWITCH
Head-to-head study powered to evaluate superiority of RINVOQ vs HUMIRA (adalimumab) in RA patients who had inadequate response or intolerance to 1 TNFi2
A 12-week, randomized, double-blind, active-comparator–controlled study of 491 adult patients with moderate to severe RA who did not respond to 1 TNFi (non-adalimumab). Designed to evaluate superiority of continuing TNFi therapy with HUMIRA (adalimumab) vs switching to RINVOQ (upadacitinib).
PRIMARY ENDPOINT2
SELECT RANKED SECONDARY ENDPOINTS2
At Week 12 vs HUMIRA:
SELECT PRESPECIFIED NONRANKED ENDPOINTS2
At all visits:
| MEAN (SD) Unless otherwise stated |
RINVOQ 15 mg QD + MTX (n=245) | HUMIRA 40 mg EOW + MTX n=246* |
|---|---|---|
| Parameter | ||
| Age (years) | 55.3 (12.7) | 55.9 (12.5) |
| Age ≥65 years, n (%) | 57 (23.3) | 72 (29.3) |
| Female, n (%) | 189 (77.1) | 191 (77.6) |
| BMI (kg/m2) | 29.4 (6.5) | 28.8 (7.0) |
| RA duration since diagnosis (years) | 10.1 (8.5) (n=244) | 10.3 (9.3) |
| Disease Characteristics | ||
| DAS28-CRP | 5.7 (0.8) (n=235) | 5.7 (0.8) (n=236) |
| DAS28-ESR | 6.3 (0.9) (n=234) | 6.4 (0.9) (n=235) |
| TJC68 | 22.4 (12.3) | 22.8 (12.6) |
| SJC66 | 15.5 (6.6) | 15.9 (8.3) |
| hsCRP (mg/L) | 16.8 (25.4) (n=245) | 14.0 (17.6) |
| ESR (mm/hr) | 37.1 (23.4) (n=243) | 38.9 (24.4) (n=245) |
| PtGA (0–10 NRS) | 7.1 (1.9) (n=235) | 7.4 (1.9) (n=236) |
| PhGA (0–10 NRS) | 7.0 (1.6) | 6.9 (1.6) |
| Pain (0–10 NRS) | 7.4 (1.9) | 7.4 (1.9) (n=232) |
| HAQ-DI | 1.6 (0.6) (n=234) | 1.6 (0.6) (n=234) |
| FACIT-Fatigue | 26.8 (11.5) (n=234) | 26.8 (10.5) (n=233) |
| Concomitant Therapies | ||
| Patients receiving oral corticosteroid at baseline, n (%) | 99 (40.4) | 100 (40.7) |
| Oral steroid dose (prednisone equivalent) at baseline (mg/day) | 6.4 (2.7) (n=99) | 6.7 (3.2) (n=100) |
| MTX dose at baseline (mg/week), median | 15.0 | 15.0 (n=245) |
| NSAIDs | 128 (52.2) | 111 (45.1) |
| Patient History, n (%) | ||
| HZ vaccination | 35 (14.6) | 31 (12.8) |
| History of VTE | 2 (0.8) | 2 (0.8) |
| History of CV event | 18 (7.3) | 11 (4.5) |
| Number of CV risk factorsa, n (%) | ||
| 0 | 72 (29.4) | 65 (26.4) |
| 1 | 94 (38.4) | 107 (43.5) |
| 2 | 58 (23.7) | 61 (24.8) |
| 3+ | 21 (8.6) | 13 (5.3) |
| CV risk factors at baseline, n (%) | ||
| Hypertension | 90 (36.7) | 85 (34.6) |
| Diabetes mellitus | 6 (2.4) | 2 (0.8) |
| History of tobacco/nicotine use (current/former) | 89 (36.3) | 77 (31.3) |
| Elevated LDL-Cb | 42 (17.1) | 65 (26.4) |
| Low HDL-Cc | 36 (14.7) | 32 (13.0) |
| Reason for discontinuation of prior TNFi, n (%) | ||
| Intolerance | 25 (10.2) | 27 (11.0) |
| Inadequate response | 220 (89.8) | 219 (89.0) |
| Type of inadequate response to prior TNFi, n (%) | ||
| Primary nonresponder | 121 (55.8) | 115 (54.0) |
| Secondary nonresponder | 96 (44.2) | 98 (46.0) |
| Missing | 3 | 6 |
| Prior TNFi administered, n (%) | ||
| Etanercept | 165 (67.3) | 170 (69.1) |
| Certolizumab | 40 (16.3) | 35 (14.2) |
| Golimumab | 24 (9.8) | 21 (8.5) |
| Infliximab | 15 (6.1) | 13 (5.3) |
| Adalimumab† | 0 | 1 (0.4) |
*Patients entered the study while receiving a stable dose of MTX (15–25 mg/week). MTX was not considered an ancillary drug in the study.2
†Protocol deviations.2
aCV risk factors included CV event, hypertension, diabetes mellitus, tobacco/nicotine use, elevated LDL-C, and lowered HDL‑C.
b≥3.36 mmol/L (ie, >129.9 mg/dL).
c<1.034 mmol/L (ie, <18.6 mg/dL).
ACR=American College of Rheumatology; BMI=body mass index; CDAI=Clinical Disease Activity Index; CRP=C-reactive protein; CV=cardiovascular; DAS28-CRP=Disease Activity Score in 28 joints using C-reactive protein; DAS28-ESR=28-joint Disease Activity Score using erythrocyte sedimentation rate; EOW=every other week; ESR=erythrocyte sedimentation rate; FACIT-Fatigue=Functional Assessment of Chronic Illness Therapy-Fatigue; HAQ-DI=Health Assessment Questionnaire-Disability Index; HDL-C=high-density lipoprotein cholesterol; hsCRP=high-sensitivity C-reactive protein; HZ=herpes zoster; IR=intolerance or inadequate response; LDA=low disease activity; LDL-C=low-density lipoprotein cholesterol; MACE=major adverse cardiovascular event; MTX=methotrexate; NSAID=nonsteroidal anti-inflammatory drug; PhGA=Physician's Global Assessment; PtGA=patient global assessment; primary nonresponder=patient who did not respond to prior TNFi treatment; QD=once daily; RA=rheumatoid arthritis; SC=subcutaneous; SD=standard deviation; SDAI=Simplified Disease Activity Index; secondary nonresponder=patient who initially responded to prior TNFi treatment but lost response over time; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; VTE=venous thromboembolism.
REFERENCES:
SELECT-EARLY
Adults with moderately to severely active RA who were MTX‑naïve1
RINVOQ is indicated for TNFi-IR patients1
Upadacitinib 30 mg is not an approved dose.
aInitially 947 patients were randomized in the study, but 2 patients were never dosed.
bX-ray images of hands and feet obtained at these time points.2
cStarting at Week 12, patients with ≤20% improvement in TJC and SJC compared to baseline at 2 consecutive visits continued blinded therapy and optimized background RA medications (corticosteroids, NSAIDs, and/or low‑potency analgesics).3,4
dAt Week 26, patients with CDAI ≤2.8 continued their original study drug; background medications (NSAIDs, corticosteroids, and/or low‑potency analgesics, and csDMARDs) were optimized in patients with CDAI >2.8 but ≥20% improvement in TJC and SJC; among patients with CDAI >2.8 and <20% improvement in TJC and SJC, RINVOQ 15 mg or upadacitinib 30 mg were added by re‑randomization according to 1:1 ratio for those initially randomized to MTX, and MTX was added for those initially randomized to RINVOQ 15 mg or upadacitinib 30 mg.2,5
eStarting at Week 48, patients who did not achieve ≥20% improvement in both TJC and SJC at 2 consecutive visits were removed from the study. Initiation of or change in background RA medications (NSAIDs, corticosteroids, low-potency analgesics, and csDMARDs; not all patients received background MTX) is allowed at anytime during Period 2.6
fFollowing a protocol amendment, all patients in the long-term extension who were previously receiving UPA 30 mg received RINVOQ 15 mg.11
PRIMARY ENDPOINT1
RANKED SECONDARY ENDPOINTS3,8
At Week 12:
At Week 24:
SELECT PRESPECIFIED NONRANKED ENDPOINTS2,3,9,10
DATA LIMITATIONS
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
BASELINE CHARACTERISTICS3
| MEAN (SD) OR N (%) | MTX n=314 | RINVOQ 15 mg QD n=317 |
|---|---|---|
| Female, n (%) | 240 (76) | 241 (76) |
| Age (years), mean (SD) | 53.3 (12.9) | 51.9 (12.6) |
| Duration since RA diagnosis (years), mean (SD) | 2.6 (5.1) | 2.9 (5.4) |
| RF+ and/or ACPA+, n (%) | 255 (81) | 279 (88) |
| MTX exposure, n (%) | 19 (6) | 30 (9.5) |
| csDMARD exposure, n (%) | 79 (25) | 80 (25) |
| Oral glucocorticoid use, n (%) | 163 (52) | 147 (46) |
| - Dose (mg),* mean (SD) | 6.4 (2.4) | 6.4 (3.1) |
| TJC68, mean (SD) | 26.4 (16.2) | 25.4 (14.4) |
| SJC66, mean (SD) | 16.9 (10.6) | 16.9 (10.4) |
| PtGA (0–100 mm VAS), mean (SD) | 65.8 (21.5) | 66.6 (22.0) |
| PhGA (0–100 mm VAS), mean (SD) | 68.7 (16.5) | 67.1 (17.0) |
| Pain (0–100 mm VAS), mean (SD) | 65.7 (21.5) | 68.4 (20.6) |
| hsCRP (mg/L), mean (SD) | 21.2 (22.1) | 23.0 (27.4) |
| DAS28-CRP, mean (SD) | 5.9 (1.0) | 5.9 (1.0) |
| HAQ-DI, mean (SD) | 1.6 (0.7) | 1.6 (0.7) |
| CDAI, mean (SD) | 40.5 (13.3) | 40.4 (13.3) |
| SDAI, mean (SD) | 42.6 (14.0) | 42.7 (13.9) |
| mTSS, mean (SD) | 13.3 (30.6) | 18.1 (38.2) |
| - Erosion Score, mean (SD) | 6.1 (15.5) | 8.6 (19.3) |
| - Joint Space Narrowing Score, mean (SD) | 7.2 (16.2) | 9.6 (20.1) |
*Prednisone equivalent dose in patients receiving oral glucocorticoids at baseline.
ACPA=anti-citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; CDAI=Clinical Disease Activity Index; CR=clinical remission; CRP=C-reactive protein; csDMARD=conventional synthetic disease-modifying antirheumatic drug; DAS28-CRP=28-joint disease activity score using C-reactive protein; HAQ-DI=Health Assessment Questionnaire Disability Index; hsCRP=high-sensitivity C-reactive protein; IR=intolerance or inadequate response; JE=joint erosion; JSN=joint space narrowing; LDA=low disease activity; mTSS=modified total Sharp score; MTX=methotrexate; NSAID=nonsteroidal anti-inflammatory drug; PhGA=Physician's Global Assessment; PtGA=patient global assessment; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=Simplified Disease Activity Index; SF-36 (PCS)=36-item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; UPA=upadacitinib; VAS=visual analog scale.
REFERENCES:
SELECT-NEXT
Adults with moderately to severely active RA who had an inadequate response to csDMARD(s)1
RINVOQ is indicated for TNFi-IR patients1
Upadacitinib 30 mg is not an approved dose.
aStarting at Week 24, patients who did not achieve CDAI ≤10 could have initiated or adjusted corticosteroids, NSAIDs, acetaminophen, or ≤2 csDMARDs. Patients who failed to show ≥20% improvement in TJC and SJC compared to baseline at 2 consecutive visits were removed from the study.4
bFollowing a protocol amendment, all patients in the long-term extension received UPA 15 mg QD, including those previously on UPA 30 mg.7
PRIMARY ENDPOINT1
RANKED SECONDARY ENDPOINTS5,6
At Week 12:
SELECT PRESPECIFIED NONRANKED ENDPOINTS6
DATA LIMITATIONS
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
BASELINE CHARACTERISTICS3
| MEAN (SD) OR N (%) | PBO + csDMARDs n=221 | RINVOQ 15 mg QD + csDMARDs n=221 |
|---|---|---|
| Female, n (%) | 166 (75) | 182 (82) |
| Age (years), mean (SD) | 56.0 (12.2) | 55.3 (11.5) |
| Duration since RA diagnosis (years), mean (SD) | 7.2 (7.5) | 7.3 (7.9) |
| RF+ and/or ACPA+, n (%) | 181 (82) | 184 (83) |
| csDMARD use at baseline | ||
| - MTX alone, n (%) | 141 (64) | 122 (55) |
| - MTX plus other csDMARD, n (%) | 49 (22) | 47 (21) |
| - csDMARD other than MTX, n (%) | 30 (14) | 51 (23) |
| - Missing, n (%) | 1 (<1) | 1 (<1) |
| Prior bDMARD exposure, n (%) | 29 (13) | 27 (12) |
| Oral glucocorticoid use, n (%) | 106 (48) | 96 (43) |
| - Oral glucocorticoid dose* (mg), mean (SD) | 6.3 (2.6) | 6.0 (2.4) |
| TJC68, mean (SD) | 24.7 (15.0) | 25.2 (13.8) |
| SJC66, mean (SD) | 15.4 (9.2) | 16.0 (10.0) |
| PtGA (0–100 mm VAS), mean (SD) | 60.3 (20.5) | 63.1 (21.9) |
| PhGA (0–100 mm VAS), mean (SD) | 64.4 (17.7) | 64.3 (16.2) |
| Pain (0–100 mm VAS), mean (SD) | 61.5 (20.8) | 64.1 (19.5) |
| hsCRP (mg/L), mean (SD) | 12.6 (14.0) | 16.6 (19.2) |
| DAS28-CRP, mean (SD) | 5.6 (0.8) | 5.7 (1.0) |
| HAQ-DI, mean (SD) | 1.4 (0.6) | 1.5 (0.6) |
| CDAI, mean (SD) | 37.8 (11.8) | 38.3 (11.9) |
| SDAI, mean (SD) | 39.0 (11.9) | 39.9 (12.5) |
*Based on prednisone equivalent.
ACPA=anti-citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; bDMARD=biologic disease-modifying antirheumatic drug; CDAI=Clinical Disease Activity Index; CR=clinical remission; CRP=C-reactive protein; csDMARD=conventional synthetic disease-modifying antirheumatic drug; DAS28-CRP=28-joint disease activity score using C-reactive protein; HAQ-DI=Health Assessment Questionnaire Disability Index; hsCRP=high-sensitivity C-reactive protein; IR=intolerance or inadequate response; JE=joint erosion; JSN=joint space narrowing; LDA=low disease activity; MTX=methotrexate; NSAID=nonsteroidal anti-inflammatory drug; PBO=placebo; PhGA=Physician's Global Assessment; PtGA=patient global assessment; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=Simplified Disease Activity Index; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; UPA=upadacitinib; VAS=visual analog scale.
REFERENCES:
US-RNQR-260103
RINVOQ vs
HUMIRA® (adalimumab)
SELECT-SWITCH Study in RA
Explore head-to-head data for RINVOQ vs HUMIRA in moderate to severe rheumatoid arthritis patients who have had an inadequate response or intolerance to 1 TNFi.
