For moderate to severe rheumatoid arthritis (RA) in adult TNFi-IR patients1
Well-studied
safety profile1
Data from 5 robust Phase 3 clinical trials
Adverse Events of Special Interest1,5
Patients could advance or switch to RINVOQ from placebo, or be rescued
to RINVOQ from active comparator or placebo as early as Week 12
depending on the study design.1
*TEAE=treatment-emergent adverse event is defined as any adverse event with an onset date on or after the first dose of study drug and no more than 30 days after the last dose of study drug if subject discontinued study drug prematurely.5
SAFETY CONSIDERATIONS
Consider the benefits and risks for the individual patient
prior to initiating therapy with RINVOQ
WARNINGS & PRECAUTIONS
consistent SAFETY PROFILE OF AEs
OBSERVED IN LONG-TERM ANALYSIS2,6
Phase 3 Program AEs2,6-9,*
Any RINVOQ 15 mg QD†
(E/100 PYs unless otherwise stated)
Adverse reaction rates observed in clinical trials and LTE studies may not predict the rates observed in clinical practice.
ADVERSE REACTIONS: The most common adverse reactions in RA RINVOQ clinical trials (≥1%) were upper respiratory tract infections, nausea, cough, pyrexia, pneumonia, herpes zoster, herpes simplex, and oral candidiasis.1
LONG-TERM SAFETY DATA ACROSS 7 INDICATIONS1-3,6,*
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| RHEUMATOLOGY | DERMATOLOGY | GASTROENTEROLOGY | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| RA | PsA | AS | nr-axSpA | AD | UC | CD | ||||
| TEAE OF SPECIAL INTERESTa (E/100 PY unless otherwise noted) | RINVOQ 15 mg | RINVOQ 15 mg | RINVOQ 30 mg | RINVOQ 15 mg | RINVOQ 30 mg | RINVOQ 15 mg | RINVOQ 30 mg | |||
| (N=3209, PY=10782.7) | (N=907, PY=2426.4) | (N=596, PY=939.1) | (N=286, PY=323.9) | (N=1340, PY=3055.3) | (N=1353, PY=3231.0) | (N=285, PY=504.1) | (N=291, PY=549.7) | (N=221, PY=295.8) | (N=739, PY=1179.2) | |
| INFECTIONS | ||||||||||
| Serious infection | 3.6 | 3.9 | 2.6 | 0.9 | 2.2 | 2.8 | 3.6 | 4.5 | 3.0 | 7.1 |
| Opportunistic infection (excluding TB and herpes zoster) |
0.3 | 0.4 | 0.2 | 0 | 1.8 | 2.4 | 0.4 | 0.5 | 0.7 | 0.4 |
| Active TB | <0.1 | 0 | 0 | 0 | <0.1 | <0.1 | 0 | 0 | 0 | <0.1 |
| Herpes zoster | 3.2 | 3.1 | 2.8 | 1.9 | 3.1 | 5.8 | 4.8 | 6.4 | 3.0 | 4.8 |
| MALIGNANCYb | ||||||||||
| Malignancy (excluding NMSC) | 0.7 | 0.7 | 0.2 | 0.3 | 0.4 | 0.3 | 0.4 | 0.5 | 0.7 | 0.9 |
| Lymphoma | <0.1 | 0.1c | 0.1c | 0.3 | <0.1 | <0.1 | 0 | 0 | 0 | 0.2 |
| NMSC | 0.4 | 0.7 | 0.2 | 0.3 | 0.4 | 0.3 | 0 | 1.1 | 0 | 0.5 |
| CARDIOVASCULAR EVENTSb | ||||||||||
| Adjudicated MACEd | 0.3 | 0.2 | 0.1 | 0.3 | <0.1 | <0.1 | 0 | 0.4 | 0 | 0.2 |
| Adjudicated VTEe | 0.4 | 0.2 | 0.3 | 0.6 | <0.1 | <0.1 | 0.8 | 0.7 | 0 | 0.3 |
| GASTROENTEROLOGICAL EVENTSb | ||||||||||
| Adjudicated gastrointestinal perforations | <0.1 | <0.1 | 0 | 0 | 0 | 0 | 0 | 0 | 0.3 | 0.4 |
Adverse reaction rates observed in clinical trials may not fully characterize the risks of RINVOQ. Certain adverse events may require longer observation periods and longer-term patient exposure to ascertain risk.
RINVOQ is taken once daily.
Well-studied
safety profile1
Common Adverse Reactions
Infections
- In the placebo‑controlled studies
SELECT-BEYOND, SELECT-NEXT, and
SELECT-COMPARE through 12/14 weeks, infections were reported in 20.9% of patients treated with placebo and 27.4% in patients treated with RINVOQ 15 mg.11 - In the 12-month exposure dataset, the incidence rate of infection was 83.8 per 100 patient-years for patients treated with RINVOQ 15 mg.11
aPatients were on background MTX or csDMARDS.
bURTI includes: acute sinusitis, laryngitis, nasopharyngitis, oropharyngeal pain, pharyngitis, pharyngotonsillitis, rhinitis, sinusitis, tonsillitis, viral upper respiratory tract infection.
Lab Monitoring and Dosing
considerations1
TREATMENT WITH RINVOQ SHOULD NOT BE INITIATED, OR SHOULD BE INTERRUPTED IF:
*Treatment can be initiated or restarted after levels return above specified values, drug-induced liver injury diagnosis is excluded, or infection is controlled.
In RA, PsA, AS, and nr-axSpA:
No dose adjustment is required for mild, moderate or severe renal impairment.1
No dose adjustment is required for mild or moderate hepatic impairment.1
RINVOQ is not recommended in patients with:
- Active hepatitis B or hepatitis C
- Severe hepatic impairment (Child‑Pugh C)
RINVOQ has not been studied in end-stage renal disease (eGFR <15 mL/min/1.73m2)
HYPERSENSITIVITY:1 RINVOQ is contraindicated in patients with known hypersensitivity to upadacitinib or any of its excipients. If a clinically significant hypersensitivity reaction occurs, discontinue RINVOQ and institute appropriate therapy.
Lab Abnormalities from
the Controlled Period
of
the RA Phase 3 program
(Week 12 or 14)1
Neutropenia: Decreases in absolute neutrophil count (<1000 cells/mm3) occurred in 1.1% of patients treated with RINVOQ in the first 3 months of exposure.
Lymphopenia: Decreases in lymphocyte counts (<500 cells/mm3) occurred in 0.9% of patients treated with RINVOQ in the first 3 months of exposure.
Anemia: Hemoglobin decreases below 8 g/dL in at least one measurement occurred in <0.1% of patients treated with RINVOQ in the first 3 months of exposure.
Lipid Elevations:Increases in lipid parameters including total cholesterol, triglycerides, low‑density lipoproteins, and high‑density lipoproteins were observed in patients treated with RINVOQ. Elevations in LDL and HDL cholesterol peaked by Week 8 and remained stable thereafter.
Liver Enzyme Elevations: Confirmed increases in liver enzyme levels >3 times the upper limit of normal were observed in patients treated with RINVOQ.
Creatine Phosphokinase Elevations: Increases in creatine phosphokinase (CPK) levels >5 times the upper limit of normal were observed in patients treated with RINVOQ. Most elevations >5x ULN were transient and did not require treatment discontinuation.
Study Design & Baseline Characteristics
SELECT-BEYOND
Adults with moderately to severely active RA who had an inadequate response or intolerance to bDMARDs1
RINVOQ is indicated for TNFi-IR patients
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 two 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
- ACR20 response at Week 12
Ranked Secondary Endpoints6,7
At Week 12:
- Change from baseline in DAS28-CRP
- Change from baseline in HAQ-DI
- Proportion of patients achieving DAS28-CRP≤3.2 (LDA)
- Change from baseline in SF-36 (PCS)
Select Prespecified nonranked endpoints7
- ACR20, ACR50 and ACR70 response at all visits (except those that were ranked timepoints)
- ACR20 response at Week 1
- Proportion of patients achieving CR based on DAS28‑CRP, DAS28‑ESR, SDAI, and CDAI at all visits
- Proportion of patients achieving Boolean criteria at Week 12
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
*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; bDMARDs=biologic disease‑modifying antirheumatic drugs; 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; hsCRP=high‑sensitivity C‑reactive protein; HAQ‑DI=health assessment questionnaire disability index; IL-6=interleukin 6; 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; 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; VAS=visual analog scale
REFERENCES
1. RINVOQ [package insert]. North Chicago, IL: AbbVie Inc.
2. Genovese MC, Fleischmann R, Combe B, et al. Supplement - Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease‑modifying anti‑rheumatic drugs (SELECT‑BEYOND): a double‑blind, randomised controlled phase 3 trial. Lancet. 2018;391(10139):2513‑2524.
3. Genovese MC, Combe B, Hall S, et al. Upadacitinib in patients with rheumatoid arthritis and inadequate response or intolerance to biologic DMARDs: results at 60 weeks from the SELECT‑BEYOND Study. Poster presented at: The European Congress of Rheumatology, 12‑15 June 2019, Madrid, Spain.
4. Data on File. ABVRRTI68669.
5. Data on File. ABVRRTI68670.
6. Genovese MC, Fleischmann R, Combe B, et al. Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease‑modifying anti‑rheumatic drugs (SELECT‑BEYOND): a double‑blind, randomised controlled phase 3 trial. Lancet. 2018;391(10139):2513‑2524.
7. Data on File. ABVRRTI68842.
8. A study to compare upadacitinib (ABT-494) to placebo in adults with rheumatoid arthritis on stable dose of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) with an inadequate response or intolerance to biologic DMARDs (SELECT-BEYOND). ClinicalTrials.gov identifier: NCT02706847. https://clinicaltrials.gov/ct2/show/NCT02706847. Updated August 2, 2021. Accessed November 30, 2021.
US-MULT-220500
SELECT‑EARLY
Adults with moderately to severely active RA who were MTX‑naïve1
RINVOQ is indicated for TNFi-IR patients
Upadacitinib 30 mg is not an approved dose.
aInitially 947 patients were randomized in the study, but two patients were never dosed.2
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 two 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 two 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 UPA 15 mg.11
Primary Endpoint1
- ACR50 response at Week 12
Ranked Secondary Endpoints3,8
At Week 12:
- Change from baseline in DAS28-CRP
- Change from baseline in HAQ-DI
- Proportion of patients achieving DAS28-CRP≤3.2 (LDA)
- Change from baseline in SF-36 (PCS)
At Week 24:
- Change from baseline in mTSS
- Proportion of patients achieving DAS28-CRP<2.6 (CR)
Select prespecified
nonranked endpoints2,3,9,10
- ACR20/50/70 at all visits (except those that were ranked timepoints)
- Change from baseline in mTSS at Week 24, Week 48, and Week 96
- Proportion of patients with no radiographic progression (mTSS ≤0) at Week 24, Week 48, and Week 96
- Change from baseline in JE and JSN score at Week 24, Week 48, and Week 96
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
*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; csDMARDs=conventional synthetic disease-modifying antirheumatic drugs; DAS28-CRP=28 joint disease activity score using C-reactive protein; HAQ-DI=health assessment questionnaire disability index; hsCRP=high-sensitivity C-reactive protein; JE=joint erosion score; JSN=joint space narrowing; LDA=low disease activity; mTSS=modified total Sharp score; MTX=methotrexate; NSAIDs=nonsteroidal anti-inflammatory drugs; 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; VAS=visual analog scale
REFERENCES
1. RINVOQ [package insert]. North Chicago, IL: AbbVie Inc.
2. Van Vollenhoven R, Takeuchi T, Pangan AL, et al. Supplement: Efficacy and safety of upadacitinib monotherapy in methotrexate‑naïve patients with moderately to severely active rheumatoid arthritis (SELECT‑EARLY): a randomized, double-blind, active‑comparator, multi‑center, multi‑country trial. Arthritis Rheumatol. 2020. doi:10.1002/art.41384.
3. Van Vollenhoven R, Takeuchi T, Pangan AL, et al. Efficacy and safety of upadacitinib monotherapy in methotrexate‑naïve patients with moderately to severely active rheumatoid arthritis (SELECT‑EARLY): a randomized, double‑blind, active‑comparator, multi-center, multi‑country trial. Arthritis Rheumatol. 2020. doi:10.1002/art.41384.
4. Data on File. ABVRRTI70661.
5. Data on File. ABVRRTI68563.
6. Data on File. ABVRRTI70953.
7. Van Vollenhoven R, Takeuchi T, Rischmueller M, et al. Upadacitinib monotherapy in methotrexate‑naïve patients with rheumatoid arthritis: results at 72 weeks from SELECT‑EARLY. Poster presented at: The European Congress of Rheumatology, 3‑6 June 2020, E-Congress.
8. Data on File. ABVRRTI68564.
9. Data on File. ABVRRTI70539.
10. Data on File. ABVRRTI70954.
11. A study to compare upadacitinib (ABT-494) monotherapy to methotrexate (MTX) monotherapy in adults with rheumatoid arthritis (RA) who have not previously taken methotrexate (SELECT-EARLY). ClinicalTrials.gov identifier: NCT02706873. https://clinicaltrials.gov/ct2/show/NCT02706873. Updated August 2, 2021. Accessed November 30, 2021.
US-MULT-220500
SELECT-MONOTHERAPY
Adults with moderately to severely active RA who had an inadequate response to MTX1
RINVOQ is indicated for TNFi-IR patients
Upadacitinib 30 mg is not an approved dose.
aPatients on MTX 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.7
Primary Endpoint1
- ACR20 response at Week 14
Select Ranked Secondary Endpoints3,6
At Week 14:
- Change from baseline in DAS28-CRP
- Change from baseline in HAQ-DI
- Change from baseline in SF-36 (PCS)
- Proportion of patients achieving DAS28-CRP≤3.2 (LDA)
- Proportion of patients achieving DAS28-CRP<2.6 (CR)
SELECT PRESPECIFIED NONRANKED ENDPOINTS3,6
- ACR50 and ACR70 response at Week 14
- Proportion of patients achieving CR based on DAS28‑CRP <2.6, DAS28-ESR <2.6, SDAI ≤3.3, CDAI ≤2.8, and Boolean criteria at all visits (except those that were ranked timepoints)
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
*Prior to receiving study drug. In the control arm, patients continued prior MTX dose as blinded study drug.
†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; csDMARDs=conventional synthetic disease‑modifying antirheumatic drugs; 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; LDA=low disease activity; MTX=methotrexate; NSAIDs=nonsteroidal anti‑inflammatory drugs; 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; VAS=visual analog scale
REFERENCES
1. RINVOQ [package insert]. North Chicago, IL: AbbVie Inc.
2. Smolen JS, Pangan AL, Emery P, et al. Supplement - Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate (SELECT‑MONOTHERAPY): a randomised, placebo‑controlled, double‑blind phase 3 study. Lancet. 2019;393(10188):2303-2311.
3. Smolen JS, Pangan AL, Emery P, et al. Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate (SELECT‑MONOTHERAPY): a randomised, placebo‑controlled, double‑blind phase 3 study. Lancet. 2019;393(10188):2303-2311.
4. Smolen JS, Emery P, Rigby W, et al. Upadacitinib as monotherapy in patients with rheumatoid arthritis: results at 48 weeks from the SELECT‑MONOTHERAPY study. Poster presented at: The European Congress of Rheumatology, 12‑15 June 2019, Madrid, Spain.
5. Data on File. ABVRRTI68979.
6. Data on File. ABVRRTI68841.
7. A study comparing upadacitinib (ABT-494) monotherapy to methotrexate (MTX) monotherapy in adults with rheumatoid arthritis (RA) who have an inadequate response to MTX (SELECT-MONOTHERAPY). ClinicalTrials.gov identifier: NCT02706951. https://clinicaltrials.gov/ct2/show/NCT02706951. Updated August 2, 2021. Accessed November 30, 2021.
US-MULT-220500
SELECT-NEXT
Adults with moderately to severely active RA who had an inadequate response to csDMARD(s)1
RINVOQ is indicated for TNFi-IR patients
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
- ACR20 response at Week 12
Select Ranked Secondary Endpoints5,6
At Week 12:
- Proportion of patients achieving DAS28-CRP≤3.2 (LDA)
- Proportion of patients achieving DAS28-CRP<2.6 (CR)
- Proportion of patients achieving CDAl≤10 (LDA)
Select Prespecified nonranked endpoints6
- ACR50 and ACR70 response at Week 12
- ACR20 response at Week 1
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 Characteristics5
*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 anti-rheumatic 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; 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; VAS=visual analog scale.
REFERENCES
1. RINVOQ [package insert]. North Chicago, IL: AbbVie Inc.
2. Burmester GR, Kremer JM, Van den Bosch F, et al. Supplement - Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease‑modifying anti‑rheumatic drugs (SELECT‑NEXT): a randomised, double‑blind, placebo‑controlled phase 3 trial. Lancet. 2018;391(10139):2503‑2512.
3. Burmester GR, Van den Bosch F, Bessette L, et al. Long‑term safety and efficacy of upadacitinib in patients with rheumatoid arthritis and an inadequate response to csDMARDs: results at 60 weeks from the SELECT‑NEXT study. Poster presented at: The European Congress of Rheumatology, 12‑15 June 2019, Madrid, Spain.
4. Data on File. ABVRRTI68981.
5. Burmester GR, Kremer JM, Van den Bosch F, et al. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease‑modifying anti‑rheumatic drugs (SELECT‑NEXT): a randomised, double‑blind, placebo‑controlled phase 3 trial. Lancet. 2018;391(10139):2503‑2512.
6. Data on File. ABVRRTI68843.
7. Data On File. ABVRRTI73233.
US-MULT-220500
SELECT-COMPARE
Adults with moderately to severely active RA who had an inadequate response to MTX1
RINVOQ is indicated for TNFi-IR patients
aX-ray imaging was performed at these time points; Week 14 for non-responder 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
- ACR20 response: RINVOQ 15 mg + MTX vs Placebo + MTX at Week 12
SELECT RANKED SECONDARY ENDPOINTS2
At Week 12 vs Placebo + MTX:
- Change from baseline in DAS28-CRP
- Change from baseline in HAQ-DI
- Change from baseline in SF-36 (PCS)
- Proportion of patients achieving DAS28-CRP≤3.2 (LDA)
- Proportion of patients achieving DAS28-CRP<2.6 (CR)
At Week 26 vs Placebo + MTX:
- Change from baseline mTSS
SELECT PRESPECIFIED NONRANKED ENDPOINTS3,9,10
- ACR20/50/70 response rates and change from baseline in individual ACR components at all visits (except those that were ranked timepoints).
- Proportion of patients achieving CR based on DAS28-CRP, DAS28-ESR, SDAI, CDAI, and Boolean criteria at all visits (except those that were ranked timepoints).
- Proportion of patients with no radiographic progression (mTSS ≤0) at Week 26, Week 48, and Week 96.
- Change from baseline in mTSS at Week 26, Week 48, and Week 96.
- Change from baseline in joint space narrowing score and joint erosion score at Week 26, Week 48, and Week 96.
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 CHARACTERISTICS3,11
*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; bDMARDs=biologic disease‑modifying antirheumatic drugs; CDAI=clinical disease activity index; 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; LDA=low disease activity; mTSS=modified total Sharp score; MTX=methotrexate; 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; VAS=visual analog scale
REFERENCES
1. RINVOQ [package insert]. North Chicago, IL: AbbVie Inc.
2. Fleischmann R, Pangan AL, Song I-H, et al. Supplement - Upadacitinib versus placebo or adalimumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase III, double‑blind, randomized controlled trial. Arthritis Rheumatol. 2019;71(11):1788‑1800.
3. Fleischmann R, Pangan AL, Song I-H, et al. Upadacitinib versus placebo or adalimumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase III, double‑blind, randomized controlled trial. Arthritis Rheumatol. 2019;71(11):1788‑1800.
4. Data on File. ABVRRTI70534.
5. Data on File. ABVRRTI70955.
6. Data on File. ABVRRTI68439.
7. Upadacitinib meets all primary and ranked secondary endpoints including superiority versus adalimumab in phase 3 study in rheumatoid arthritis. AbbVie Inc. https://news.abbvie.com/news/upadacitinib-meets-all-primary-and-ranked-secondary-endpoints-including-superiority-versus-adalimumab-in-phase-3-study-in-rheumatoid-arthritis.htm. April 9, 2018. August 15, 2019.
8. Fleishmann R, Mysler E, Bessette L, et al. Long-term safety and efficacy of upadacitinib or adalimumab in patients with rheumatoid arthritis results at 3 years from the SELECT-COMPARE study. Poster presented at: the American College of Rheumatology Convergence, 5-9 November 2021. E-Congress.
9. Data On File. ABVRRTI68440.
10. Data on File. ABVRRTI70956.
11. Fleischmann R, Pangan AL, Mysler E, et al. A phase 3, randomized, double‑blind study comparing upadacitinib to placebo and to adalimumab, in patients with active rheumatoid arthritis with inadequate response to methotrexate. Oral presentation at: The ACR annual meeting 2018, 19–24 October 2018, Chicago, USA.
US-MULT-220500
SELECT-CHOICE
Adults with moderately to severely active RA and inadequate response or intolerance to bDMARDs.1
RINVOQ is indicated for TNFi-IR patients
aAfter the initial dose, active comparator® IV was administered at 2 and 4 weeks, then every 4 weeks thereafter. The last dose occurred at Week 20. Weight‑based dosing was as follows: <60 kg: 500 mg; 60 - 100 kg: 750 mg; >100 kg: 1000 mg.2
bStarting at Week 12, patients who did not achieve ≥20% improvement in both TJC and SJC compared to baseline at 2 consecutive visits were to have background medication(s) (corticosteroids, NSAIDs, acetaminophen or adding or increasing doses in csDMARD(s)) adjusted or added.1,3
Primary Endpoint1
- Change from baseline DAS28‑CRP at Week 12 (noninferiority) against a margin of 0.6
DATA LIMITATIONS
Data not labeled as a ranked secondary endpoint were prespecified nonranked endpoints not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
Baseline Characteristics1
*Did not receive any of the protocol-specified bDMARDs prior to entry.
†Based on prednisone equivalent.
ACPA=anti-citrullinated protein antibody; ACR=American College of Rheumatology; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; bDMARD=biological disease-modifying anti-rheumatic drug; CDAI=clinical disease activity index; CR=clinical remission; CRP=C-reactive protein; DAS28-CRP=28 joint disease score using C-reactive protein; DAS28-ESR=28 joint disease activity score using erythrocyte sedimentation rate; ESR=erythrocyte sedimentation rate; EULAR=European League Against Rheumatism; IV=intravenous; LDA=low disease activity; QD=once per day; 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
REFERENCES
1. Rubbert‑Roth A, Enejosa J, Pangan AL, et al. Efficacy and Safety of Upadacitinib vs Abatacept in Patients With Active Rheumatoid Arthritis and Prior Inadequate Response or Intolerance to Biologic Disease‑Modifying Anti‑Rheumatic Drugs (SELECT‑CHOICE): A Double‑Blind, Randomized Controlled Phase 3 Trial. Poster presented at: The European Congress of Rheumatology, 3‑6 June 2020, E‑Congress.
2. Rubbert-Roth A, Enejosa J, Pangan AL, et al. Efficacy and Safety of Upadacitinib vs Abatacept in Patients with Active Rheumatoid Arthritis and Prior Inadequate Response or Intolerance to Biologic Disease‑Modifying Anti‑Rheumatic Drugs (SELECT‑CHOICE): A Double‑Blind, Randomized Controlled Phase 3 Trial. Ann Rheum Dis 2020,79(Supp 1):1011.
3. Data on File. ABVRRTI70957.
4. Data on File. ABVRRTI71850.
US-MULT-220500
BASELINE CHARACTERISTICS1
RA Clinical Program Integrated Long-Term Analysis
(~6.5 years of exposure as of August 15, 2022)1-3
Adults with moderately to severely active RA
RINVOQ was studied in RA patients with various comorbidities
>75% of patients had at least 1 CV risk factor*
>35% were current or former smokers
~59% of patients were ≥50 years of age with ≥1 CV risk factor*
Consider the benefits and risks for individual patients prior to initiating or continuing therapy with RINVOQ, particularly in current or past smokers and those who are ≥50 years of age with at least 1 CV risk factor.
*CV risk factors included CV event, hypertension, diabetes mellitus, tobacco/nicotine use, elevated LDL-C, and lowered HDL-C.3
aN=3192 (UPA 15 mg).
bThis includes any CV events (both MACEs and other CV events).
c≥3.36 mmol/L (ie. ≥129.9 mg/dL).
d<1.034 mmol/L (ie. <18.6 mg/dL).
ACPA=anti-citrullinated protein antibody; bDMARD=biological disease-modifying antirheumatic drug; CRP=C-reactive protein; csDMARD=conventional synthetic disease-modifying anti-rheumatic drug; CV=cardiovascular; DAS28-CRP=disease activity score 28 joints; HDL-C=high-density lipoprotein cholesterol; HZ=herpes zoster; LDL-C=low-density lipoprotein cholesterol; MACE=major adverse cardiovascular event; MTX=methotrexate; PY=patient-years; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; UPA=upadacitinib; VTE=venous thromboembolism
REFERENCES
1. Cohen SB, Van Vollenhoven R, Curtis JR, et al. Integrated safety profile of upadacitinib with up to 4.5 years of exposure in patients with rheumatoid arthritis. Poster presented at: The European Congress of Rheumatology, 2-5 June 2021, E-Congress.
2. Data on File. ABVRRTI74922.
3. Data on File. ABVRRTI75013.
US-MULT-220887
