Upadacitinib is an investigational oral selective JAK1 inhibitor currently in Phase 3 clinical trials to treat rheumatoid arthritis (RA), psoriatic arthritis (PsA) and Crohn’s disease.1 It is also being investigated to treat ulcerative colitis, ankylosing spondylitis, atopic dermatitis and giant cell arteritis.
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Results from the first phase of the ongoing SELET-COMPARE study have been announced. This 12 week, Phase 3, multicenter, randomized, double-blind study evaluated the efficacy and safety of upadacitinib.1 During the trial, 15 mg once-daily upadacitinib was compared with placebo and adalimumab in adult patients with moderate to severe RA receiving stable background methotrexate with an inadequate response. Patients receiving methotrexate were randomized 2:2:1 to receive 15 mg once-daily upadacitinib (n=651), placebo (n=651) or 40 mg adalimumab given as a subcutaneous injection every other week (n=327).
During this first phase, the study’s primary endpoints were the percentage of patients who achieve ACR20 and clinical remission (based on DAS28[CRP]) at Week 12 compared with placebo-treated patients. Secondary endpoints were a change in the modified total Sharp score; the percentage of patients who achieved ACR50, low disease activity, changes in pain measured by the Patient’s Assessment of Pain (based on VAS); and changes in physical function measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI) for upadacitinib-treated patients compared with both placebo- and adalimumab-treated patients.
Week 12 Results
Upadacitnib-treated patients met both primary endpoints, with 71% achieving an ACR20 response at Week 12, compared with 63% for adalimumab-treated patients and 36% for placebo-treated patients. Twenty-nine percent of upadacitinib-treated patients achieved clinical remission in this timeframe compared with 18% of adalimumab-treated patients and 6% of placebo-treated patients.
All secondary endpoints were also met at Week 12. Significantly more upadacitinib-treated patients (45%) achieved low disease activity compared with only 29% of adalimumab-treated patients and 14% of placebo-treated patients. Additionally, 45% of upadacitinib-treated patients achieved ACR50 compared with 29% of adalimumab-treated patients and 14% of placebo-treated patients. ACR70 responses were 25% for upadacitinib-treated patients, 13% for adalimumab-treated patients and 5% for placebo-treated patients.
Week 26 & Beyond
At Week 26, upadacitinib significantly inhibited radiographic progression compared with placebo (n=593, P<0.001). No new safety signals were identified during the study, and the safety profile was consistent with previously reported results.
The SELET-COMPARE trial is ongoing and includes a 48-week, randomized, double-blind treatment period followed by a long-term extension study of up to five years.
Michele B. Kaufman, PharmD, BCGP, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.