FDA Approves Upadacitinib for RA

In August, the U.S. Food and Drug Administration (FDA) approved upadacitinib (Rinvoq) to treat adults with moderate to severe active rheumatoid arthritis (RA) who are methotrexate intolerant or for whom methotrexate was inadequate. The treatment is a once daily, oral Janus kinase (JAK) inhibitor and is approved in a 15 mg dose. This approval was based on data from the phase 3 SELECT program, which assessed more than 4,400 RA patients in five studies.¹

In the SELECT program, upadacitnib met all primary and ranked secondary endpoints. Additionally, upadacitinib-treated patients significantly inhibited radiographic progression, with or without methotrexate.

The Findings
In the SELECT-COMPARE trial, approximately 30% of upadacitinib-treated patients achieved clinical remission at Week 12, assessed by Disease Activity Score (DAS) 28 CRP score of less than 2.6, vs. 6% of placebo plus methotrexate-treated patients. By Week 14 of the SELECT-MONOTHERAPY trial only 8% of placebo plus methotrexate-treated patients achieved clinical remission. In SELECT-EARLY clinical trial, 52% of upadacitinib-treated patients who were methotrexate-naive achieved ACR50 at Week 12 compared with 28% of methotrexate-treated patients. Additionally at Week 12, 36% of upadacitinib-treated patients achieved clinical remission according to the DAS28-CRP vs. 14% of placebo plus methotrexate-treated patients.

Durable remission rates were seen up to Week 26. In the SELECT-EARLY trial, 48% of upadacitinib-treated monotherapy patients achieved clinical remission at Week 24 vs. 9% of placebo plus methotrexate-treated patients. Also 41% of upadacitinib plus methotrexate-treated patients in the SELECT-COMPARE trial achieved clinical remission at Week 26 compared with 18% of placebo plus methotrexate-treated patients. At Weeks 24 and 26, analyses were not controlled for multiple comparisons.

Inhibition of radiographic progression was measured by the change in modified total Sharp score (mTSS) from baseline compared with methotrexate through Week 24 in SELECT-EARLY and for upadacitinib plus MTX-treated patients compared with placebo plus MTX-treated patients in SELECT-COMPARE trial through Week 26. In the clinical trials, the most common side effects were cough, nausea, pyrexia and upper respiratory tract infection.

Upadacitinib is also being investigated to treat other immune-mediated diseases. The European Medicines Agency, as well as regulatory authorities in Canada and Japan, are evaluating upadacitinib for treating adults with moderate to severe active RA.

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.

Reference

1. AbbVie Inc. New releases: AbbVie receives FDA qpproval of Rinvoq (upadacitinib), an oral JAK inhibitor for the treatment of moderate to severe rheumatoid arthritis. 2019 Aug 16.