Phase 3
Completed N=1,002
A Study to Compare Upadacitinib (ABT-494) Monotherapy to Methotrexate (MTX) Monotherapy in Adults With Rheumatoid Arthritis (RA) Who Have Not Previously Taken Methotrexate
Source: ClinicalTrials.gov NCT02706873 ↗Enrolled (actual)
1,002
Serious AEs
16.0%
Results posted
Oct 2019
Primary outcomePrimary: Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 - Global Analysis — 28.3; 52.1; 56.4 percentage of participants — p=<0.001
◆ Published Evidence
Established
51citations · ~17 / year
Safety profile of upadacitinib in patients at risk of cardiovascular disease: integrated post hoc analysis of the SELECT phase III rheumatoid arthritis clinical programme.
Summary
The objectives of Period 1 were the following:
* To compare the safety and efficacy of upadacitinib 7.5 mg once daily (QD) monotherapy (for participants in Japan only), 15 mg QD monotherapy, and 30 mg QD monotherapy versus weekly methotrexate monotherapy for the treatment of signs and symptoms of RA in methotrexate-naïve adults with moderately to severely active RA;
* To compare the efficacy of upadacitinib 15 mg QD monotherapy and upadacitinib 30 mg QD monotherapy versus weekly methotrexate monotherapy for prevention of structural progression in methotrexate-naïve adults with moderately to severely active RA.
The objective of Period 2 is to evaluate the long-term safety, tolerability, and efficacy of upadacitinib 7.5 mg QD (for participants in Japan only), 15 mg QD, and 30 mg QD in adults with RA who have completed Period 1.
Linked Publications (5)
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Safety profile of upadacitinib in patients at risk of cardiovascular disease: integrated post hoc analysis of the SELECT phase III rheumatoid arthritis clinical programme.
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MACE and VTE across upadacitinib clinical trial programmes in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis.
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Malignancy in the Upadacitinib Clinical Trials for Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, and Non-radiographic Axial Spondyloarthritis.
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Safety Profile of Upadacitinib: Descriptive Analysis in Over 27,000 Patient-Years Across Rheumatoid Arthritis, Psoriatic Arthritis, Axial Spondyloarthritis, Atopic Dermatitis, and Inflammatory Bowel Disease.
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Upadacitinib monotherapy versus methotrexate monotherapy in patients with rheumatoid arthritis: efficacy and safety through 5 years in the SELECT-EARLY randomized controlled trial.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 - Global Analysis |
28.3; 52.1; 56.4 | <0.001 sig |
| PRIMARY Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 24 - Global Analysis |
18.5; 48.3; 50.0 | <0.001 sig |
| PRIMARY Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 - Global Analysis |
54.1; 75.7; 77.1 | <0.001 sig |
| PRIMARY Change From Baseline in Modified Total Sharp Score (mTSS) at Week 24 - Global Analysis |
0.67; 0.14; 0.07 | 0.001 sig |
| SECONDARY Change From Baseline in DAS28 (CRP) at Week 12 - Global Analysis |
-1.85; -2.73; -2.85 | <0.001 sig |
| SECONDARY Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 - Global Analysis |
-0.49; -0.83; -0.86 | <0.001 sig |
| SECONDARY Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12 - Global Analysis |
28.3; 53.3; 54.8 | <0.001 sig |
| SECONDARY Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12 - Global Analysis |
5.74; 9.99; 10.08 | <0.001 sig |
| SECONDARY Change From Baseline in DAS28 (CRP) at Week 24 - Global Analysis |
-2.15; -3.07; -3.34 | <0.001 sig |
| SECONDARY Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 24 - Global Analysis |
-0.60; -0.87; -0.91 | <0.001 sig |
| SECONDARY Percentage of Participants With an ACR50 Response at Week 24 - Global Analysis |
33.4; 60.3; 65.6 | <0.001 sig |
| SECONDARY Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 24 - Global Analysis |
32.2; 59.9; 65.0 | <0.001 sig |
| SECONDARY Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 24 - Global Analysis |
6.97; 10.70; 11.39 | <0.001 sig |
| SECONDARY Percentage of Participants With No Radiographic Progression at Week 24 - Global Analysis |
77.7; 87.5; 89.3 | 0.002 sig |
| SECONDARY Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12 - Global Analysis |
14.0; 32.5; 36.9 | <0.001 sig |
| SECONDARY Percentage of Participants With an ACR20 Response at Week 24 - Global Analysis |
58.6; 78.9; 78.0 | <0.001 sig |
| SECONDARY Percentage of Participants With an ACR70 Response at Week 24 - Global Analysis |
18.5; 44.5; 49.7 | <0.001 sig |
| SECONDARY Percentage of Participants With an ACR20 Response at Week 12 - Japan Sub-study |
57.1; 85.5; 85.2; 78.6 | 0.004 sig |
| SECONDARY Percentage of Participants With an ACR50 Response at Week 12 - Japan Sub-study |
21.4; 60.0; 66.7; 71.4 | <0.001 sig |
| SECONDARY Percentage of Participants With an ACR70 Response at Week 12 - Japan Sub-study |
0.0; 34.5; 51.9; 64.3 | <0.001 sig |
| SECONDARY Change From Baseline in DAS28 (CRP) at Week 12 - Japan Sub-study |
-1.42; -2.86; -3.28; -3.34 | <0.001 sig |
| SECONDARY Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 - Japan Sub-study |
-0.20; -0.75; -0.95; -0.95 | <0.001 sig |
| SECONDARY Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12 - Japan Sub-study |
2.87; 8.84; 10.79; 9.63 | <0.001 sig |
| SECONDARY Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12 - Japan Sub-study |
17.9; 69.1; 77.8; 78.6 | <0.001 sig |
| SECONDARY Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 24 - Japan Sub-study |
17.9; 67.3; 70.4; 82.1 | <0.001 sig |
| SECONDARY Change From Baseline in Modified Total Sharp Score (mTSS) at Week 24 - Japan Sub-study |
2.64; 0.95; 0.24; 0.19 | 0.063 |
| SECONDARY Percentage of Participants With No Radiographic Progression at Week 24 - Japan Sub-study |
46.2; 82.4; 80.8; 79.2 | 0.001 sig |
Eligibility Criteria
Inclusion Criteria
- Duration of symptoms consistent with RA for ≥ 6 weeks who also fulfill the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA.
- Naïve to Methotrexate (MTX) or, if already on MTX, have received no more than 3 weekly MTX doses with requirement to complete a 4-week MTX washout before the first dose of study drug.
- Participants with prior exposure to conventional synthetic disease-modifying anti-rheumatic drugs(csDMARDs) other than MTX may be enrolled if completed the washout period.
- Participant meets both of the following minimum disease activity criteria:
-≥ 6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits.
- high sensitivity C reactive protein (hsCRP) ≥ 5 mg/L (central lab, upper limit of normal [ULN] 2.87 mg/L at Screening Visit.
- Greater than or equal to 1 bone erosion on x-ray (by local reading) OR in the absence of documented bone erosion, both positive rheumatoid factor (RF) and positive anti-cyclic citrullinated peptide (anti CCP) autoantibodies are required at Screening.
- Stable dose of non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, oral corticosteroids (equivalent to prednisone ≤ 10 mg/day), or inhaled corticosteroids for stable medical conditions are allowed but must have been at a stable dose ≥ 1 week prior to the first dose of study drug.
Exclusion Criteria
- Intolerant to Methotrexate (MTX).
- Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib).
- Prior exposure to any biologic disease-modifying anti-rheumatic drugs (bDMARDs).
- History of any arthritis with onset prior to age 17 years or current diagnosis, inflammatory joint disease other than RA (including but not limited to gout, systemic lupus erythematosus, psoriatic arthritis, axial spondyloarthritis including ankylosing spondylitis and non-radiographic axial spondyloarthritis, reactive arthritis, overlap connective tissue diseases, scleroderma, polymyositis, dermatomyositis, fibromyalgia [currently with active symptoms]. Current diagnosis of secondary Sjogren's Syndrome is permitted.
- Has been treated with intra-articular, intramuscular, intravenous, trigger point or tender point, intra-bursa, or intra-tendon sheath corticosteroids in the preceding 8 weeks prior to the first dose of study drug.
Data sourced from ClinicalTrials.gov (NCT02706873) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.