AbbVie announced positive top-line results from the Phase 3 SELECT-PsA 1 clinical trial. In this study, both doses of RINVOQTM (upadacitinib; 15 mg and 30 mg, once daily) met the primary endpoint of ACR20 response at week 12 versus placebo in adult patients with active psoriatic arthritis who have responded inadequately or are intolerant to one or more non-biologic disease modifying anti-rheumatic drugs (DMARDs). RINVOQ also demonstrated significant improvements in signs and symptoms of the disease across a variety of endpoints compared to placebo. RINVOQ, a selective and reversible JAK inhibitor discovered and developed by AbbVie, is being studied as a once-daily therapy in psoriatic arthritis and multiple immune-mediated inflammatory diseases.
"Patients living with psoriatic arthritis often suffer from joint pain, stiffness and fatigue, impacting their ability to work and lead a physically active life," said Michael Severino, M.D., vice chairman and president, AbbVie. "The results of this large Phase 3 study further support the potential of RINVOQ to help these patients. We look forward to sharing these data with regulatory bodies around the world to support our application for label expansion for RINVOQ to include adult patients with active psoriatic arthritis."
Results show that at week 12, 71 percent and 79 percent of patients receiving 15 mg and 30 mg of RINVOQ achieved ACR20, respectively, compared to 36 percent of patients receiving placebo (p<0.0001). In terms of ACR20 response at week 12 versus adalimumab, both RINVOQ doses achieved non-inferiority and only the 30 mg dose showed superiority.1 ACR50 at week 12 was achieved by 38 percent and 52 percent of patients receiving 15 mg and 30 mg of RINVOQ, respectively, compared to 13 percent of patients receiving placebo (nominal p<0.0001). In addition, 16 percent and 25 percent of patients receiving 15 mg and 30 mg of RINVOQ achieved ACR70, respectively, at week 12 compared to 2 percent of the placebo group (nominal p<0.0001).
Patients receiving RINVOQ also had greater improvements in physical function at week 12, as measured by the Health Assessment Questionnaire Disability Index (HAQ-DI). Patients in the 15 mg and 30 mg RINVOQ groups reported a -0.42 and -0.47 change from baseline in HAQ-DI score, respectively, compared to -0.14 on placebo (p<0.0001). RINVOQ also showed improvement in skin symptoms at week 16, with 63 percent and 62 percent of patients receiving 15 mg and 30 mg of RINVOQ achieving a 75 percent improvement in the Psoriasis Area Severity Index (PASI 75), respectively, compared to 21 percent on placebo (p<0.0001). Minimal disease activity (MDA) at week 24 was achieved in 37 percent and 45 percent of 15 mg and 30 mg RINVOQ-treated patients, respectively, versus 12 percent of the placebo group (p<0.0001).
"The results of SELECT-PsA 1 showed that both doses of upadacitinib demonstrated significantly greater efficacy in joint and skin symptoms, as well as inhibition of radiographic progression, compared to placebo," said Professor Iain McInnes, F.R.C.P., Ph.D., University of Glasgow Institute of Infection, Immunity & Inflammation. "These data are encouraging and add to the growing body of evidence that upadacitinib has the potential to improve outcomes for people living with psoriatic arthritis."
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Following 24 weeks of treatment, RINVOQ at 15 mg and 30 mg significantly inhibited radiographic progression, as measured by the change from baseline in modified PsA Sharp/van der Heijde Score, compared to placebo (p<0.01). The inhibition of joint damage is important for psoriatic arthritis patients as this can impact physical function and disability.
The safety profile of RINVOQ was consistent with that observed in previously reported studies, with no new safety risks detected. Through week 24, serious infections occurred in 1.2 percent and 2.6 percent of patients in the 15 mg and 30 mg RINVOQ groups, respectively, compared to 0.9 percent in the placebo group and 0.7 percent in the adalimumab group. There was one case of adjudicated venous thromboembolic events (VTE) in the RINVOQ 30 mg group (0.2 percent), no cases in the RINVOQ 15 mg group, two cases in the adalimumab group (0.5 percent) and one case in the placebo group (0.2 percent). No major adverse cardiovascular events (MACE) were reported in either RINVOQ group. There was one MACE reported in the placebo group and two MACE reported in the adalimumab group. There were no deaths in either RINVOQ group, one death in the placebo group (0.2 percent) and no deaths in the adalimumab group.
Psoriatic arthritis is a heterogeneous systemic inflammatory disease with hallmark manifestations in joints and skin, affecting more than 50 million people worldwide. In psoriatic arthritis, the immune system creates inflammation that can lead to pain, fatigue and stiffness in the joints.
Results from the SELECT-PsA 1 study will be presented at a future medical meeting and published in a peer-reviewed publication.
SELECT-PsA 1 is a Phase 3, multicenter, randomized, double-blind, parallel-group, active and placebo-controlled study designed to evaluate the safety and efficacy of RINVOQ compared to placebo and adalimumab in adult patients with active psoriatic arthritis who have a history of inadequate response to at least one non-biologic DMARD. Patients were randomized to RINVOQ 15 mg, RINVOQ 30 mg, adalimumab (40 mg EOW) or placebo followed by either RINVOQ 15 mg or RINVOQ 30 mg at week 24.
The primary endpoint was the percentage of subjects receiving RINVOQ 15 mg or 30 mg who achieved an ACR20 response after 12 weeks of treatment versus placebo. Ranked secondary endpoints included change from baseline in HAQ-DI at week 12, proportion of patients achieving PASI 75 at week 16 and proportion of patients achieving MDA at week 24. The trial is ongoing, and the long-term extension remains blinded to evaluate the long-term safety, tolerability and efficacy of the two once-daily doses (15 mg and 30 mg) of RINVOQ in patients who have completed the placebo-controlled period.
Discovered and developed by AbbVie, RINVOQ is a selective and reversible JAK inhibitor studied in several immune-mediated inflammatory diseases. In August 2019, RINVOQ received U.S. Food and Drug Administration approval for adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate. In December 2019, RINVOQ also received approval by the European Commission for the treatment of adult patients with moderate to severe active rheumatoid arthritis who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs. Phase 3 trials of RINVOQ in rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, Crohn's disease, atopic dermatitis, ulcerative colitis and giant cell arteritis are ongoing.