For active ankylosing spondylitis (AS) in adult TNFi-IR patients1
For active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation in adult TNFi-IR patients1
US-MULT-230356
US-MULT-230356
For active ankylosing spondylitis (AS) in adult TNFi-IR patients1
For active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation in adult TNFi-IR patients1
For moderate to severe rheumatoid arthritis (RA) in adult TNFi-IR patients1
For active psoriatic arthritis (PsA) in adult TNFi-IR patients1
*Includes 3 phase 2 and 6 phase 3 RA trials, 2 phase 3 PsA trials, 1 phase 2/3 AS trial, 1 phase 3 AS trial, 1 phase 3 nr-axSpA trial, 1 phase 2 and 3 phase 3 AD trials, and 3 phase 3 UC trials. RA: RINVOQ 15 mg, upadacitinib 30 mg; PsA: RINVOQ 15 mg, upadacitinib 30 mg; AS: RINVOQ 15 mg; nr-axSpA: RINVOQ 15 mg; AD: RINVOQ 15 mg and 30 mg; UC: RINVOQ 15 mg, 30 mg, and 45 mg. RINVOQ 15 mg is the approved dose in RA, PsA, AS, and nr-axSpA; RINVOQ 15 mg and 30 mg are the approved doses in AD; RINVOQ 15 mg, 30 mg and 45 mg are the approved doses in UC.1,2
†In PsA: ~5.0 years maximum exposure (~2.9 years median) to RINVOQ 15 mg as of 08/2022. In AS: ~3.8 years maximum exposure (~1.7 years median) to RINVOQ 15 mg as of 08/2022. In nr-axSpA: ~2.4 years maximum exposure (~1.0 years median) to RINVOQ 15 mg as of 08/2022.2
AD=atopic dermatitis; AS=ankylosing spondylitis; IR=intolerance or inadequate response; JAK=Janus kinase; max.=maximum; nr-axSpA=non-radiographic axial spondyloarthritis; PsA=psoriatic arthritis; RA=rheumatoid arthritis; TNFi=tumor necrosis factor inhibitor; UC=ulcerative colitis
Adverse events of
special interest 3-6
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*Mixed=67% bDMARD-naïve & 33% bDMARD-IR9
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.
Adverse events of
special interest 7,8
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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.
<< Swipe table to see more
Overall, the safety profile observed in patients with active AS and nr-axSpA treated with RINVOQ 15 mg is consistent with the safety profile observed in patients with RA and PsA.1
Most Common Adverse Reactions from RINVOQ clinical trials
ANKYLOSING SPONDYLITIS9
Most Common Adverse Reactions from SELECT-AXIS 2 Study 1 (14 Weeks)
Adverse reactions reported in >2% of ankylosing spondylitis patients treated with
RINVOQ 15 mg from the placebo-controlled study.9
aAS patients could be on background NSAIDs.
Infections
ADVERSE REACTIONS: The most common adverse reactions in RINVOQ clinical trials were upper respiratory tract infections, herpes zoster, herpes simplex, bronchitis, nausea, cough, pyrexia, acne, headache, increased blood creatine phosphokinase, hypersensitivity, folliculitis, abdominal pain, increased weight, influenza, fatigue, neutropenia, myalgia, influenza-like illness, elevated liver enzymes, and rash.1
Inform patients that retinal detachment has been reported in clinical trials with RINVOQ. Advise patients to immediately inform their healthcare provider if they develop any sudden changes in vision while receiving RINVOQ.1
NON-RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS10
Most Common Adverse Reactions from SELECT-AXIS 2 Study 2 (14 Weeks)
Adverse reactions reported in >2% of non-radiographic axial spondyloarthritis patients
treated with RINVOQ 15 mg from the placebo-controlled study.10
anr-axSpA patients could be on background NSAIDs.
Infections
ADVERSE REACTIONS: The most common adverse reactions in RINVOQ clinical trials were upper respiratory tract infections, herpes zoster, herpes simplex, bronchitis, nausea, cough, pyrexia, acne, headache, increased blood creatine phosphokinase, hypersensitivity, folliculitis, abdominal pain, increased weight, influenza, fatigue, neutropenia, myalgia, influenza-like illness, elevated liver enzymes, and rash.1
Inform patients that retinal detachment has been reported in clinical trials with RINVOQ. Advise patients to immediately inform their healthcare provider if they develop any sudden changes in vision while receiving RINVOQ.1
PSORIATIC ARTHRITIS11
Most Common Adverse Reactions from SELECT‑PsA 1 and SELECT‑PsA 2 (24 Weeks)
Adverse reactions reported in >1% of psoriatic arthritis patients treated with
RINVOQ 15 mg pooled from the placebo‑controlled studies.11
aPsA patients could be on background non-biologic DMARDs.1
Infections
ADVERSE REACTIONS: The most common adverse reactions in RINVOQ clinical trials were upper respiratory tract infections, herpes zoster, herpes simplex, bronchitis, nausea, cough, pyrexia, acne, headache, increased blood creatine phosphokinase, hypersensitivity, folliculitis, abdominal pain, increased weight, influenza, fatigue, neutropenia, myalgia, influenza-like illness, elevated liver enzymes, and rash.1
Inform patients that retinal detachment has been reported in clinical trials with RINVOQ. Advise patients to immediately inform their healthcare provider if they develop any sudden changes in vision while receiving RINVOQ.1
RHEUMATOID ARTHRITIS1
Most Common Adverse Reactions from SELECT-BEYOND,
SELECT-COMPARE, and
SELECT-NEXT (12 Weeks)1
Adverse reactions reported in ≥1% of moderate to severe rheumatoid arthritis
patients treated with RINVOQ 15 mg pooled from the placebo‑controlled studies.
aRA patients were on background MTX or csDMARDs.
bURTI includes: acute sinusitis, laryngitis, nasopharyngitis, oropharyngeal pain, pharyngitis, pharyngotonsillitis, rhinitis, sinusitis, tonsillitis, viral upper respiratory tract infection.
Infections
ADVERSE REACTIONS: The most common adverse reactions in RINVOQ clinical trials were upper respiratory tract infections, herpes zoster, herpes simplex, bronchitis, nausea, cough, pyrexia, acne, headache, increased blood creatine phosphokinase, hypersensitivity, folliculitis, abdominal pain, increased weight, influenza, fatigue, neutropenia, myalgia, influenza-like illness, elevated liver enzymes, and rash.1
Inform patients that retinal detachment has been reported in clinical trials with RINVOQ. Advise patients to immediately inform their healthcare provider if they develop any sudden changes in vision while receiving RINVOQ.1
Treatment with RINVOQ should not be initiated, or should be interrupted if:
Absolute neutrophil count
<1000 cells/mm3*
Absolute lymphocyte count
<500 cells/mm3*
Hemoglobin levels
<8 g/dL*
Liver enzyme elevations
and a
drug-induced liver
injury is suspected*
Patient has or develops
a serious or
opportunistic infection*
*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:1
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.
Neutropenia: Decreases in absolute neutrophil count (<1000 cells/mm3) were associated with RINVOQ treatment.
Lymphopenia: Decreases in lymphocyte count (<500 cells/mm3) were reported with RINVOQ treatment.
Anemia: Hemoglobin decreases below 8 g/dL were reported with RINVOQ treatment.
Lipid Elevations: Increases in lipid parameters including total cholesterol, triglycerides, LDL, and HDL were observed in patients treated with RINVOQ. Elevations in LDL and HDL cholesterol peaked by Week 8 and remained stable thereafter.
Liver Enzyme Elevations: Increased incidences in liver enzyme elevations were associated with RINVOQ compared to placebo.
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RINVOQ is indicated for the treatment of:
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.
Limitations of Use: RINVOQ is not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, or other immunosuppressants.
Limitations of Use: RINVOQ is not recommended for use in combination with other JAK inhibitors, biological therapies for ulcerative colitis or Crohn’s disease, or with potent immunosuppressants such as azathioprine and cyclosporine.
REFERENCES
Adults with active AS who had an inadequate response or intolerance to at least two NSAIDs and inadequate response to bDMARD therapy1,2
RINVOQ is indicated for TNFi-IR patients
Primary Endpoint1,3
SELECT MULTIPLICITY-CONTROLLED KEY SECONDARY ENDPOINTS (RINVOQ vs Placebo at Week 14)3
PRESPECIFIED ADDITIONAL ENDPOINTS (RINVOQ vs Placebo at Week 14)3
DATA LIMITATIONS2
Data labeled as a primary and ranked secondary endpoint at Week 14 were multiplicity-controlled. All other comparisons were not adjusted for multiplicity; therefore, statistical significance has not been established.
*Patients randomized into the study and receiving concomitant oral corticosteroids or NSAIDs must have been on a stable dose for at least 14 days prior to the baseline visit, while those receiving concomitant conventional synthetic DMARDs were required to be on a stable dose for at least 28 days prior to the baseline visit.
†At least 40% improvement and an absolute improvement of ≥2 units on a scale of 0 to 10 from baseline in at least 3 of the 4 domains, with no worsening in the fourth domain: Total back pain, inflammation (mean score of BASDAI questions 5 and 6 on severity and duration of morning stiffness), physical function (BASFI), and Patient Global Assessment of disease activity. NRI-MI means nonresponder imputation incorporating multiple imputation to handle missing data due to COVID-19.
‡Back pain defined on a numeric rating scale (0-10) based on the following question, “What is the amount of back pain that you experienced at any time during the last week?”
§Inflammation defined as the mean of the BASDAI questions 5 and 6 on severity and duration of morning stiffness.
BASELINE CHARACTERISTICS2,4
*China, Taiwan, South Korea, and Japan.
†Australia, Israel, and New Zealand.
‡Assessed in 208 participants in the placebo group and 211 participants in the upadacitinib group.
§Assessed in 202 participants in the placebo group and 199 participants in the upadacitinib group with available baseline MRI data up to 3 days after first dose of study drug.
AS=ankylosing spondylitis; ASAS=Assessment of SpondyloArthritis international Society; ASAS40=≥40% improvement and an absolute improvement from baseline of ≥2 units on a scale of 0 to 10 in at least 3 of the 4 domains, with no worsening in the fourth domain: total back pain, inflammation (mean score of BASDAI questions 5 and 6 on severity and duration of morning stiffness), physical function (BASFI), and Patient Global Assessment of disease activity; ASDAS=Ankylosing Spondylitis Disease Activity Score; BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; BASDAI50=a ≥50% improvement in BASDAI score from baseline; BASFI=Bath Ankylosing Spondylitis Functional Index; bDMARD=biologic disease-modifying antirheumatic drug; COVID-19=coronavirus disease-2019; CRP=C-reactive protein; DMARD=disease-modifying antirheumatic drug; HLA=human leukocyte antigen; hs-CRP=high-sensitivity C-reactive protein; IR=intolerance or inadequate response; NRS=numeric rating scale; NSAID=nonsteroidal anti-inflammatory drug; QD=once per day; SD=standard deviation; SPARCC=Spondyloarthritis Research Consortium of Canada; TNFi=tumor necrosis factor inhibitor; ULN=upper limit of normal
REFERENCES
US-MULT-221344
Adults with active nr-axSpA who had an inadequate response or intolerance to at least two NSAIDs and to one bDMARD therapy in 33%.1,2
RINVOQ is indicated for TNFi-IR patients
Primary Endpoint1,2
SELECT MULTIPLICITY-CONTROLLED KEY SECONDARY ENDPOINTS (RINVOQ vs Placebo at Week 14)2
PRESPECIFIED ADDITIONAL ENDPOINTS (RINVOQ vs Placebo at Week 14)1,2
RESCUE CRITERIA3
After visit assessments were performed at Week 24 and through Week 52, patients who did not achieve an ASAS20 response at any 2 consecutively scheduled visits were rescued by adding or modifying background medications.
DATA LIMITATIONS2
Data labeled as a primary and ranked secondary endpoint at Week 14 were multiplicity-controlled. All other comparisons were not adjusted for multiplicity; therefore, statistical significance has not been established.
*Patients randomized into the study and receiving concomitant oral corticosteroids or NSAIDs must have been on a stable dose for at least 14 days prior to the baseline visit, while those receiving concomitant conventional synthetic DMARDs were required to be on a stable dose for at least 28 days prior to the baseline visit.
†314 patients were enrolled and 313 patients received study drug.
‡At least 40% improvement and an absolute improvement of ≥2 units on a scale of 0 to 10 from baseline in at least 3 of the 4 domains, with no worsening in the fourth domain: Total back pain, inflammation (mean score of BASDAI questions 5 and 6 on severity and duration of morning stiffness), physical function (BASFI), and Patient Global Assessment of disease activity. NRI-MI means nonresponder imputation incorporating multiple imputation to handle missing data due to COVID-19.
§Back pain defined on a numeric rating scale (0-10) based on the following question, “What is the amount of back pain that you experienced at any time during the last week?”
||Inflammation defined as the mean of the BASDAI questions 5 and 6 on severity and duration of morning stiffness.
BASELINE CHARACTERISTICS2,4
*China, Japan, South Korea, and Taiwan.
†Australia and Israel.
‡Three patients who had protocol deviations with both TNF inhibitor and IL-17 inhibitor exposure.
§Assessed in 155 participants in the placebo group and 154 participants in the upadacitinib group.
||Inflammation defined as the mean of the BASDAI questions 5 and 6 on severity and duration of morning stiffness.
¶Sacroiliac joint score assessed in 148 participants in the placebo group and 142 participants in the upadacitinib group; spine score assessed in 147 participants in the placebo group and 139 participants in the upadacitinib group; with available baseline MRI data up to 3 days after the first dose of study drug; MRI scored using the SPARCC 6-discovertebral unit method for the spine.
**MRI-positive defined as active sacroilitis according to the ASAS/Outcome Measures in Rheumatology Clinical Trials definition; hs-CRP-positive defined as C-reactive protein greater than the upper limit of normal (2.87 mg/L).
ASAS=Assessment of SpondyloArthritis international Society; ASDAS=Ankylosing Spondylitis Disease Activity Score; BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; BASFI=Bath Ankylosing Spondylitis Functional Index; bDMARD=biologic disease-modifying antirheumatic drug; csDMARDs=conventional synthetic disease-modifying antirheumatic drugs; HLA-B27= human leukocyte antigen B27; hs-CRP=high-sensitivity C-reactive protein; IL-17i=interleukin-17 inhibitor; MRI=magnetic resonance imaging; nr-axSpA=non-radiographic axial spondyloarthritis; NRS=numerical rating scale; NSAID=nonsteroidal anti-inflammatory drug; QD=once daily; SPARCC=Spondyloarthritis Research Consortium of Canada; TNFi=tumor necrosis factor inhibitor; ULN=upper limit of normal
REFERENCES
US-MULT-221344
Adults with active AS who had an inadequate response or intolerance to at least two NSAIDs and were bio-naïve1
RINVOQ is indicated for TNFi-IR patients
Primary Endpoint1,2
SELECT MULTIPLICITY-CONTROLLED KEY SECONDARY ENDPOINTS (RINVOQ vs placebo
at Week 14)2
SELECT PRESPECIFIED NONRANKED ENDPOINTS2
Additional efficacy analyses include the following endpoints at the scheduled time points other than those specified for the primary and key secondary variables:
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.
*At least 40% improvement and an absolute improvement of ≥2 units on a scale of 0 to 10 from baseline in at least 3 of the 4 domains, with no worsening in the fourth domain: Total back pain, inflammation (mean score of BASDAI questions 5 and 6 on severity and duration of morning stiffness), physical function (BASFI), and Patient Global Assessment of disease activity.
†Consists of patient reported outcomes about back pain [BASDAI question 2], peripheral pain or swelling [BASDAI question 3], duration of morning stiffness [BASDAI question 6], the Patient Global Assessment of disease activity, and hs-CRP.
‡Back pain defined on a numeric rating scale (0–10) based on the following question, “What is the amount of back pain that you experienced at any time during the last week?”
§Inflammation defined as the mean of the BASDAI questions 5 and 6 on severity and duration of morning stiffness.
BASELINE CHARACTERISTICS2,3
*13 patients from Japan (seven in placebo; six in upadacitinib) the other 13 patients from Asia were from South Korea.
†1 patient did not have previous NSAID therapy due to contraindications to NSAID therapy (warfarin use due to history of deep venous thrombosis and pulmonary embolism approximately 10 years before entering the study).
‡92 in the upadacitinib group; back pain defined on a numeric rating scale (0–10) based on the following question, “What is the amount of back pain that you experienced at any time during the last week?”
§91 in the upadacitinib group.
||92 in the upadacitinib group; inflammation defined as mean of BASDAI questions 5 and 6.
¶92 in the upadacitinib group.
AS=ankylosing spondylitis; ASAS=Assessment of SpondyloArthritis international Society; ASAS40=≥40% improvement and an absolute improvement from baseline of ≥2 units on a scale of 0 to 10 in at least 3 of the 4 domains, with no worsening in the fourth domain: total back pain, inflammation (mean score of BASDAI questions 5 and 6 on severity and duration of morning stiffness), physical function (BASFI), and Patient Global Assessment of disease activity; ASDAS=Ankylosing Spondylitis Disease Activity Score; BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; BASDAI50=a ≥50% improvement in BASDAI score from baseline; BASFI=Bath Ankylosing Spondylitis Functional Index; bDMARD=biologic disease-modifying antirheumatic drug; CRP=C-reactive protein; csDMARD=conventional synthetic disease modifying anti-rheumatic drug; DMARD=disease-modifying antirheumatic drug; HLA=human leukocyte antigen; hs-CRP=high-sensitivity C-reactive protein; IR= intolerance or inadequate response; MTX=methotrexate; NRS=numeric rating scale; NSAID=nonsteroidal anti-inflammatory drug; PsA=psoriatic arthritis; QD=once per day; RA=rheumatoid arthritis; SD=standard deviation; TNFi=tumor necrosis factor inhibitor; ULN=upper limit of normal
REFERENCES
US-MULT-221344
Adverse Events of Special Interest1-5
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aRates shown are n/100 PY=number of subjects with at least one event per 100 PY.1,2,4
bVTE: Venous thromboembolisms include deep vein thrombosis (DVT) and pulmonary embolism (PE).1
cMACE defined as cardiovascular death, myocardial infarction and stroke.1
*In RA studies, 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.6
†Included RINVOQ monotherapy and combination therapy with csDMARDs across 6 trials.6,7
‡TEAE: treatment-emergent adverse event, defined as an adverse event with onset on or after the first dose of study drug and up to 30 days after the last dose of RINVOQ.2
AE=adverse event; csDMARDs=conventional synthetic disease-modifying antirheumatic drugs; E/100 PYs=events per 100 patient-years; GI=gastrointestinal; MACE=major adverse cardiovascular event; NMSC=nonmelanoma skin cancer; PYs=patient-years; QD=once per day; VTE=venous thromboembolism
REFERENCES
US-MULT-221344
Adverse Events of Special Interest1
<< Swipe table to see more
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.
TEAEs were defined as AEs with an onset date that is on or after the first dose of study drug, and no more than 30 days after the last dose of RINVOQ and placebo if subject discontinued study drug prematurely.1
an/100 PYs=study size-adjusted (SSA) number of subjects with at least one event per 100 patient years.
bReported as abnormal lymphocyte morphology and not confirmed to be lymphoma.
cVTE includes deep vein thrombosis and pulmonary embolism.1
dMACE defined as cardiovascular death, myocardial infarction and stroke.1
AE=adverse event; bDMARD=biologic disease-modifying antirheumatic drug; DMARD=disease-modifying antirheumatic drug; GI=gastrointestinal; IR=intolerance or inadequate response; LTE=long term extension; MACE=major adverse cardiovascular event; NMSC=nonmelanoma skin cancer; PsA=psoriatic arthritis; PYs=patient-years; QD=once per day; TB=tuberculosis; TNFi=tumor necrosis factor inhibitor; VTE=venous thromboembolism
REFERENCES
US-MULT-221344
Adults with active PsA who had an inadequate response or intolerance to ≥1 biologic DMARDs.1
RINVOQ is indicated for TNFi-IR patients
Upadacitinib 30 mg is not an approved dose for PsA.
aStarting at Week 16, patients who did not achieve ≥20% improvement in tender and/or swollen joint counts (TJC68/SJC66) compared to baseline at Weeks 12 and 16 had background medications, adjusted or initiated.3
bAt Week 24, all remaining placebo patients were switched to RINVOQ 15 mg QD or upadacitinib 30 mg QD.3
cAfter Week 16, the use of concomitant treatments for psoriasis therapies were permitted.2
dStarting at Week 36, patients who did not achieve ≥20% improvement in TJC68 and SJC66 compared to baseline at 2 consecutive visits were discontinued from the study.3
Primary Endpoint1
Select Ranked Key Secondary Endpoints3
Additional Key Secondary Endpoints3
Select Prespecified Nonranked Endpoints3
Data Limitations3
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
BASELINE CHARACTERISTICS3,4
*Patients with intolerance but not inadequate response to a biologic DMARD.
†ULN=2.87 mg/L
ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 of the 5 other core criteria, including patient and physician Global Assessments, health assessment questionnaire — disability index (HAQ‑DI), pain assessment, and high‑sensitivity C‑reactive protein (hs‑CRP); ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 of the 5 other core criteria, including patient and physician Global Assessments, health assessment questionnaire — disability index (HAQ‑DI), pain assessment, and high‑sensitivity C‑reactive protein (hs‑CRP); ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 of the 5 other core criteria, including patient and physician Global Assessments, health assessment questionnaire — disability index (HAQ‑DI), pain assessment, and high‑sensitivity C‑reactive protein (hs‑CRP); BSA=body surface area; CCP=cyclic citrullinated peptide; DMARD=disease‑modifying antirheumatic drug; HAQ-DI=health assessment questionnaire — disability index; hs-CRP=high-sensitivity C-reactive protein; IR=intolerance or inadequate response; LDI=Leeds dactylitis index; LEI=Leeds enthesitis index; MDA=minimal disease activity; MTX=methotrexate; NRS=numeric rating scale; NSAID=nonsteroidal anti‑inflammatory drug; PASI=psoriasis area severity index; PASI75/90/100=at least 75%/90%/100% improvement in psoriasis area severity score from baseline; PsA=psoriatic arthritis; QD=once per day; RF=rheumatoid factor; SD=standard deviation; SJC66=swollen joint count using 66 joints; TJC68=tender joint count using 68 joints; TNFi=tumor necrosis factor inhibitor; ULN=upper limit normal
REFERENCES
US-MULT-221344
Adults with active PsA who had an inadequate response or intolerance to ≥1 non‑biologic DMARDs1
RINVOQ is indicated for TNFi-IR patients
Upadacitinib 30 mg is not an approved dose for PsA.
aAll patients receive X‑rays of hands and feet.3
bStarting at Week 16, patients who did not achieve ≥20% improvement in tender and/or swollen joint counts (TJC68/SJC66) compared to baseline at Weeks 12 and 16 had background DMARDs, NSAIDs, acetaminophen, low potency opioids, or corticosteroids adjusted or initiated.4
cAfter Week 16, the use of concomitant treatments for psoriasis therapies were permitted.2
dAt Week 24, all remaining placebo patients were switched to RINVOQ 15 mg QD or upadacitinib 30 mg QD (1:1 ratio), regardless of response.1
eStarting at Week 36, patients who did not achieve ≥20% improvement in TJC68 and SJC66 compared to baseline at 2 consecutive visits were discontinued from the study.5
Primary Endpoint1
Select Ranked Key Secondary Endpoints3
Upadacitinib vs placebo if not otherwise specified
Additional Key Secondary Endpoints3
Upadacitinib vs placebo if not otherwise specified
Select Prespecified Nonranked Endpoints3
Additional efficacy analyses include the following endpoints at the scheduled time points other than those specified for the primary and key secondary variables:
Data Limitations2
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
BASELINE CHARACTERISTICS3,6
*ULN>2.87 mg/L
ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 of the 5 other core criteria, including patient and physician Global Assessments, health assessment questionnaire — disability index (HAQ‑DI), pain assessment, and high‑sensitivity C‑reactive protein (hs-CRP); ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 of the 5 other core criteria, including patient and physician Global Assessments, health assessment questionnaire — disability index (HAQ‑DI), pain assessment, and high‑sensitivity C‑reactive protein (hs-CRP); ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 of the 5 other core criteria, including patient and physician Global Assessments, health assessment questionnaire — disability index (HAQ‑DI), pain assessment, and high‑sensitivity C‑reactive protein (hs‑CRP); ADA=adalimumab; BMI=body mass index; BSA=body surface area; DMARD=disease‑modifying antirheumatic drug; HAQ‑DI=health assessment questionnaire — disability index; hs-CRP=high‑sensitivity C‑reactive protein; IR=intolerance or inadequate response; LDI=Leeds dactylitis index; LEI=Leeds enthesitis index; MDA=minimal disease activity; mTSS=modified total Sharp/van der Heijde score; MTX=methotrexate; NRS=numeric rating scale; NSAID=nonsteroidal anti-inflammatory drug; PASI=psoriasis area severity index; PASI75/90/100=at least 75%/90%/100% reduction in psoriasis area severity score from baseline; PsA=psoriatic arthritis; PtGA=patient’s Global Assessment; QD=once per day; SD=standard deviation; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; ULN=upper limit normal
REFERENCES
US-MULT-221344
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
At Week 12:
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=disease activity score 28 joints; ESR=erythrocyte sedimentation rate; hs-CRP=high‑sensitivity C‑reactive protein; HAQ‑DI=health assessment questionnaire disability index; IL-6=interleukin 6; IR=intolerance or inadequate response; 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 per day; 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; VAS=visual analog scale
REFERENCES
US-MULT-221344
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 was 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
At Week 12:
At Week 24:
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=disease activity score 28 joints; HAQ-DI=health assessment questionnaire disability index; hs-CRP=high-sensitivity C-reactive protein; IR=intolerance or inadequate response; 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 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 score; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; VAS=visual analog scale
REFERENCES
US-MULT-221344
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
At Week 14:
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 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
US-MULT-221344
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
Select 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 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 antirheumatic drug; DAS28=disease activity score 28 joints; HAQ-DI=health assessment questionnaire disability index; hs-CRP=high-sensitivity C-reactive protein; IR=intolerance or inadequate response; 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 per day; 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; VAS=visual analog scale
REFERENCES
US-MULT-221344
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 RINVOQ 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 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 CHARACTERISTICS3,11
*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; bDMARD=biologic disease‑modifying antirheumatic drug; CDAI=clinical disease activity index; CR=clinical remission; CRP=C‑reactive protein; DAS28=disease activity score 28 joints; EOW=every other week; ESR=erythrocyte sedimentation rate; HAQ‑DI=health assessment questionnaire disability index; hs-CRP=high-sensitivity C‑reactive protein; IR=intolerance or inadequate response; 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 score; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; VAS=visual analog scale
REFERENCES
US-MULT-221344
Adults with moderately to severely active RA and inadequate response or intolerance to bDMARDs1
RINVOQ is indicated for TNFi-IR patients
aAfter the initial dose, ORENCIA 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
At Week 12:
At Week 12:
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
*Based on prednisone equivalent.
†Did not receive any of the protocol-specified bDMARDs prior to entry.
ACPA=anti-citrullinated protein antibody; bDMARD=biologic disease-modifying anti-rheumatic drug; CDAI=clinical disease activity index; CR=clinical remission; CRP=C-reactive protein; DAS28-CRP=disease activity score 28 joints; ESR=erythrocyte sedimentation rate; IR=intolerance or inadequate response; 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 score; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor
REFERENCES
US-MULT-221344
FROM LONG-TERM ANALYSIS
For 6 Indications
<< Swipe table to see more
aCV risk factors included CV event, hypertension, diabetes mellitus, tobacco/nicotine use, elevated LDL-C, and lowered HDL-C
bIncludes current and former tobacco/nicotine use
c≥3.36 mmol/L
d<1.034 mmol/L
*Includes RINVOQ 45 mg 8-week induction responders.
AD=atopic dermatitis; BMI=body mass index; CRP=C-reactive protein; csDMARD=conventional synthetic disease-modifying antirheumatic drug; CV=cardiovascular; HDL-C=high-density lipoprotein cholesterol; HZ=herpes zoster;LDL-C=low-density lipoprotein cholesterol; MTX=methotrexate; NSAIDs=nonsteroidal anti-inflammatory drugs; PsA=psoriatic arthritis; PY=patient-year; QD=once per day; RA=rheumatoid arthritis; SD=standard deviation; UC=ulcerative colitis; UPA=upadacitinib; VTE=venous thromboembolism
REFERENCES
US-MULT-221344
Adults with active AS who had an inadequate response or intolerance to at least two NSAIDs and inadequate response to bDMARD therapy1,2
RINVOQ is indicated for TNFi-IR patients
Primary Endpoint1,3
SELECT MULTIPLICITY-CONTROLLED KEY SECONDARY ENDPOINTS (RINVOQ vs Placebo at Week 14)3
PRESPECIFIED ADDITIONAL ENDPOINTS (RINVOQ vs Placebo at Week 14)3
DATA LIMITATIONS2
Data labeled as a primary and ranked secondary endpoint at Week 14 were multiplicity-controlled. All other comparisons were not adjusted for multiplicity; therefore, statistical significance has not been established.
*Patients randomized into the study and receiving concomitant oral corticosteroids or NSAIDs must have been on a stable dose for at least 14 days prior to the baseline visit, while those receiving concomitant conventional synthetic DMARDs were required to be on a stable dose for at least 28 days prior to the baseline visit.
†At least 40% improvement and an absolute improvement of ≥2 units on a scale of 0 to 10 from baseline in at least 3 of the 4 domains, with no worsening in the fourth domain: Total back pain, inflammation (mean score of BASDAI questions 5 and 6 on severity and duration of morning stiffness), physical function (BASFI), and Patient Global Assessment of disease activity. NRI-MI means nonresponder imputation incorporating multiple imputation to handle missing data due to COVID-19.
‡Back pain defined on a numeric rating scale (0-10) based on the following question, “What is the amount of back pain that you experienced at any time during the last week?”
§Inflammation defined as the mean of the BASDAI questions 5 and 6 on severity and duration of morning stiffness.
BASELINE CHARACTERISTICS2,4
*China, Taiwan, South Korea, and Japan.
†Australia, Israel, and New Zealand.
‡Assessed in 208 participants in the placebo group and 211 participants in the upadacitinib group.
§Assessed in 202 participants in the placebo group and 199 participants in the upadacitinib group with available baseline MRI data up to 3 days after first dose of study drug.
AS=ankylosing spondylitis; ASAS=Assessment of SpondyloArthritis international Society; ASAS40=≥40% improvement and an absolute improvement from baseline of ≥2 units on a scale of 0 to 10 in at least 3 of the 4 domains, with no worsening in the fourth domain: total back pain, inflammation (mean score of BASDAI questions 5 and 6 on severity and duration of morning stiffness), physical function (BASFI), and Patient Global Assessment of disease activity; ASDAS=Ankylosing Spondylitis Disease Activity Score; BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; BASDAI50=a ≥50% improvement in BASDAI score from baseline; BASFI=Bath Ankylosing Spondylitis Functional Index; bDMARD=biologic disease-modifying antirheumatic drug; COVID-19=coronavirus disease-2019; CRP=C-reactive protein; DMARD=disease-modifying antirheumatic drug; HLA=human leukocyte antigen; hs-CRP=high-sensitivity C-reactive protein; IR=intolerance or inadequate response; NRS=numeric rating scale; NSAID=nonsteroidal anti-inflammatory drug; QD=once per day; SD=standard deviation; SPARCC=Spondyloarthritis Research Consortium of Canada; TNFi=tumor necrosis factor inhibitor; ULN=upper limit of normal
REFERENCES
US-MULT-221344
Adults with active nr-axSpA who had an inadequate response or intolerance to at least two NSAIDs and to one bDMARD therapy in 33%.1,2
RINVOQ is indicated for TNFi-IR patients
Primary Endpoint1,2
SELECT MULTIPLICITY-CONTROLLED KEY SECONDARY ENDPOINTS (RINVOQ vs Placebo at Week 14)2
PRESPECIFIED ADDITIONAL ENDPOINTS (RINVOQ vs Placebo at Week 14)1,2
RESCUE CRITERIA3
After visit assessments were performed at Week 24 and through Week 52, patients who did not achieve an ASAS20 response at any 2 consecutively scheduled visits were rescued by adding or modifying background medications.
DATA LIMITATIONS2
Data labeled as a primary and ranked secondary endpoint at Week 14 were multiplicity-controlled. All other comparisons were not adjusted for multiplicity; therefore, statistical significance has not been established.
*Patients randomized into the study and receiving concomitant oral corticosteroids or NSAIDs must have been on a stable dose for at least 14 days prior to the baseline visit, while those receiving concomitant conventional synthetic DMARDs were required to be on a stable dose for at least 28 days prior to the baseline visit.
†314 patients were enrolled and 313 patients received study drug.
‡At least 40% improvement and an absolute improvement of ≥2 units on a scale of 0 to 10 from baseline in at least 3 of the 4 domains, with no worsening in the fourth domain: Total back pain, inflammation (mean score of BASDAI questions 5 and 6 on severity and duration of morning stiffness), physical function (BASFI), and Patient Global Assessment of disease activity. NRI-MI means nonresponder imputation incorporating multiple imputation to handle missing data due to COVID-19.
§Back pain defined on a numeric rating scale (0-10) based on the following question, “What is the amount of back pain that you experienced at any time during the last week?”
||Inflammation defined as the mean of the BASDAI questions 5 and 6 on severity and duration of morning stiffness.
BASELINE CHARACTERISTICS2,4
*China, Japan, South Korea, and Taiwan.
†Australia and Israel.
‡Three patients who had protocol deviations with both TNF inhibitor and IL-17 inhibitor exposure.
§Assessed in 155 participants in the placebo group and 154 participants in the upadacitinib group.
||Inflammation defined as the mean of the BASDAI questions 5 and 6 on severity and duration of morning stiffness.
¶Sacroiliac joint score assessed in 148 participants in the placebo group and 142 participants in the upadacitinib group; spine score assessed in 147 participants in the placebo group and 139 participants in the upadacitinib group; with available baseline MRI data up to 3 days after the first dose of study drug; MRI scored using the SPARCC 6-discovertebral unit method for the spine.
**MRI-positive defined as active sacroilitis according to the ASAS/Outcome Measures in Rheumatology Clinical Trials definition; hs-CRP-positive defined as C-reactive protein greater than the upper limit of normal (2.87 mg/L).
ASAS=Assessment of SpondyloArthritis international Society; ASDAS=Ankylosing Spondylitis Disease Activity Score; BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; BASFI=Bath Ankylosing Spondylitis Functional Index; bDMARD=biologic disease-modifying antirheumatic drug; csDMARDs=conventional synthetic disease-modifying antirheumatic drugs; HLA-B27= human leukocyte antigen B27; hs-CRP=high-sensitivity C-reactive protein; IL-17i=interleukin-17 inhibitor; MRI=magnetic resonance imaging; nr-axSpA=non-radiographic axial spondyloarthritis; NRS=numerical rating scale; NSAID=nonsteroidal anti-inflammatory drug; QD=once daily; SPARCC=Spondyloarthritis Research Consortium of Canada; TNFi=tumor necrosis factor inhibitor; ULN=upper limit of normal
REFERENCES
US-MULT-221344
Adults with active PsA who had an inadequate response or intolerance to ≥1 biologic DMARDs.1
RINVOQ is indicated for TNFi-IR patients
Upadacitinib 30 mg is not an approved dose for PsA.
aStarting at Week 16, patients who did not achieve ≥20% improvement in tender and/or swollen joint counts (TJC68/SJC66) compared to baseline at Weeks 12 and 16 had background medications, adjusted or initiated.3
bAt Week 24, all remaining placebo patients were switched to RINVOQ 15 mg QD or upadacitinib 30 mg QD.3
cAfter Week 16, the use of concomitant treatments for psoriasis therapies were permitted.2
dStarting at Week 36, patients who did not achieve ≥20% improvement in TJC68 and SJC66 compared to baseline at 2 consecutive visits were discontinued from the study.3
Primary Endpoint1
Select Ranked Key Secondary Endpoints3
Additional Key Secondary Endpoints3
Select Prespecified Nonranked Endpoints3
Data Limitations3
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
BASELINE CHARACTERISTICS3,4
*Patients with intolerance but not inadequate response to a biologic DMARD.
†ULN=2.87 mg/L
ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 of the 5 other core criteria, including patient and physician Global Assessments, health assessment questionnaire — disability index (HAQ‑DI), pain assessment, and high‑sensitivity C‑reactive protein (hs‑CRP); ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 of the 5 other core criteria, including patient and physician Global Assessments, health assessment questionnaire — disability index (HAQ‑DI), pain assessment, and high‑sensitivity C‑reactive protein (hs‑CRP); ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 of the 5 other core criteria, including patient and physician Global Assessments, health assessment questionnaire — disability index (HAQ‑DI), pain assessment, and high‑sensitivity C‑reactive protein (hs‑CRP); BSA=body surface area; CCP=cyclic citrullinated peptide; DMARD=disease‑modifying antirheumatic drug; HAQ-DI=health assessment questionnaire — disability index; hs-CRP=high-sensitivity C-reactive protein; IR=intolerance or inadequate response; LDI=Leeds dactylitis index; LEI=Leeds enthesitis index; MDA=minimal disease activity; MTX=methotrexate; NRS=numeric rating scale; NSAID=nonsteroidal anti‑inflammatory drug; PASI=psoriasis area severity index; PASI75/90/100=at least 75%/90%/100% improvement in psoriasis area severity score from baseline; PsA=psoriatic arthritis; QD=once per day; RF=rheumatoid factor; SD=standard deviation; SJC66=swollen joint count using 66 joints; TJC68=tender joint count using 68 joints; TNFi=tumor necrosis factor inhibitor; ULN=upper limit normal
REFERENCES
US-MULT-221344
Adults with active PsA who had an inadequate response or intolerance to ≥1 non‑biologic DMARDs1
RINVOQ is indicated for TNFi-IR patients
Upadacitinib 30 mg is not an approved dose for PsA.
aAll patients receive X‑rays of hands and feet.3
bStarting at Week 16, patients who did not achieve ≥20% improvement in tender and/or swollen joint counts (TJC68/SJC66) compared to baseline at Weeks 12 and 16 had background DMARDs, NSAIDs, acetaminophen, low potency opioids, or corticosteroids adjusted or initiated.4
cAfter Week 16, the use of concomitant treatments for psoriasis therapies were permitted.2
dAt Week 24, all remaining placebo patients were switched to RINVOQ 15 mg QD or upadacitinib 30 mg QD (1:1 ratio), regardless of response.1
eStarting at Week 36, patients who did not achieve ≥20% improvement in TJC68 and SJC66 compared to baseline at 2 consecutive visits were discontinued from the study.5
Primary Endpoint1
Select Ranked Key Secondary Endpoints3
Upadacitinib vs placebo if not otherwise specified
Additional Key Secondary Endpoints3
Upadacitinib vs placebo if not otherwise specified
Select Prespecified Nonranked Endpoints3
Additional efficacy analyses include the following endpoints at the scheduled time points other than those specified for the primary and key secondary variables:
Data Limitations2
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
BASELINE CHARACTERISTICS3,6
*ULN>2.87 mg/L
ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 of the 5 other core criteria, including patient and physician Global Assessments, health assessment questionnaire — disability index (HAQ‑DI), pain assessment, and high‑sensitivity C‑reactive protein (hs-CRP); ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 of the 5 other core criteria, including patient and physician Global Assessments, health assessment questionnaire — disability index (HAQ‑DI), pain assessment, and high‑sensitivity C‑reactive protein (hs-CRP); ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 of the 5 other core criteria, including patient and physician Global Assessments, health assessment questionnaire — disability index (HAQ‑DI), pain assessment, and high‑sensitivity C‑reactive protein (hs‑CRP); ADA=adalimumab; BMI=body mass index; BSA=body surface area; DMARD=disease‑modifying antirheumatic drug; HAQ‑DI=health assessment questionnaire — disability index; hs-CRP=high‑sensitivity C‑reactive protein; IR=intolerance or inadequate response; LDI=Leeds dactylitis index; LEI=Leeds enthesitis index; MDA=minimal disease activity; mTSS=modified total Sharp/van der Heijde score; MTX=methotrexate; NRS=numeric rating scale; NSAID=nonsteroidal anti-inflammatory drug; PASI=psoriasis area severity index; PASI75/90/100=at least 75%/90%/100% reduction in psoriasis area severity score from baseline; PsA=psoriatic arthritis; PtGA=patient’s Global Assessment; QD=once per day; SD=standard deviation; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; ULN=upper limit normal
REFERENCES
US-MULT-221344
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
At Week 12:
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=disease activity score 28 joints; ESR=erythrocyte sedimentation rate; hs-CRP=high‑sensitivity C‑reactive protein; HAQ‑DI=health assessment questionnaire disability index; IL-6=interleukin 6; IR=intolerance or inadequate response; 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 per day; 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; VAS=visual analog scale
REFERENCES
US-MULT-221344
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
Select 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 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 antirheumatic drug; DAS28=disease activity score 28 joints; HAQ-DI=health assessment questionnaire disability index; hs-CRP=high-sensitivity C-reactive protein; IR=intolerance or inadequate response; 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 per day; 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; VAS=visual analog scale
REFERENCES
US-MULT-221344
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 RINVOQ 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 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 CHARACTERISTICS3,11
*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; bDMARD=biologic disease‑modifying antirheumatic drug; CDAI=clinical disease activity index; CR=clinical remission; CRP=C‑reactive protein; DAS28=disease activity score 28 joints; EOW=every other week; ESR=erythrocyte sedimentation rate; HAQ‑DI=health assessment questionnaire disability index; hs-CRP=high-sensitivity C‑reactive protein; IR=intolerance or inadequate response; 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 score; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; VAS=visual analog scale
REFERENCES
US-MULT-221344
US-MULT-221344
