The Food and Drug Administration (FDA) has approved Rinvoq® (upadacitinib) for the treatment of adults with moderately to severely active ulcerative colitis who have had an inadequate response or intolerance to 1 or more tumor necrosis factor (TNF) blockers.
The approval was based on data from 2 randomized, double-blind, placebo-controlled phase 3 induction studies, U-ACHIEVE (ClinicalTrials.gov Identifier: NCT02819635) and U-ACCOMPLISH (ClinicalTrials.gov Identifier: NCT03653026), and one phase 3 maintenance study, U-ACHIEVE (ClinicalTrials.gov Identifier: NCT02819635).
The studies evaluated the efficacy and safety of upadacitinib in adults with moderately to severely active ulcerative colitis who had an inadequate response, loss of response, or intolerance to oral aminosalicylates, corticosteroids, immunosuppressants, and/or biologic therapy. In the induction studies, patients were randomly assigned to receive upadacitinib 45mg or placebo once daily for 8 weeks. In the maintenance study, patients were re-randomized to receive upadacitinib 15mg, 30mg, or placebo once daily for up to 52 weeks.
Findings from all studies showed that a greater proportion of patients treated with upadacitinib achieved clinical remission (defined using the modified Mayo Score) compared with those who received placebo (primary endpoint):
- U-ACHIEVE Induction: 26% vs 5% at week 8 (P <.001);
- U-ACCOMPLISH Induction: 33% vs 4% at week 8 (P <.001);
- U-ACHIEVE Maintenance: 42% (15mg) and 52% (30mg) vs 12% at week 52 (P <.001).
Results from the maintenance study also showed that 57% and 68% of patients receiving upadacitinib 15mg or 30mg, respectively, achieved corticosteroid free remission, defined as clinical remission (per modified Mayo Score) and corticosteroid free for at least 90 days immediately preceding week 52 among patients who achieved clinical remission at the end of the induction treatment, compared with 22% of patients on placebo.
Additionally, the studies met all ranked secondary endpoints including clinical response per modified Mayo Score, endoscopic improvement (defined as endoscopic subscore of 1 or less), and histologic endoscopic mucosal improvement (defined as an endoscopic subscore of 1 or less and Geboes score of 3.1 or less).
The safety profile of upadacitinib was consistent with that seen in previous studies across indications. There were no new safety risks identified. Adverse reactions reported during induction or maintenance included upper respiratory tract infections, increased blood creatine phosphokinase, acne, neutropenia, elevated liver enzymes, and rash.
Rinvoq, a Janus kinase (JAK) inhibitor, will be available in 45mg extended-release tablets in a 28-count bottle. Rinvoq is also approved for the treatment of rheumatoid arthritis, psoriatic arthritis, and atopic dermatitis.
- Rinvoq® (upadacitinib) receives FDA approval for the treatment of adults with moderately to severely active ulcerative colitis. News release. AbbVie. Accessed March 16, 2022. https://www.prnewswire.com/news-releases/rinvoq-upadacitinib-receives-fda-approval-for-the-treatment-of-adults-with-moderately-to-severely-active-ulcerative-colitis-301504545.html
- Rinvoq. Package insert. AbbVie; 2022. Accessed March 16, 2022. https://www.rxabbvie.com/pdf/rinvoq_pi.pdf