The USFDA has given marketing authorisation for upadacitinib (Rinvoq) to treat adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to methotrexate (MTX-IR). Upadacitinib is a once-daily oral Janus kinase (JAK) inhibitor.
The FDA approval of upadacitinib is supported by data from the SELECT programme, one of the largest registrational phase 3 programmes in RA with approximately 4,400 patients evaluated across all treatment arms in five studies.
The studies include assessments of efficacy, safety and tolerability across a variety of RA patients, including those who failed or were intolerant to biologic disease-modifying anti-rheumatic drugs and who were naïve or inadequate responders to methotrexate.
The drug is not indicated for methotrexate-naïve patients.
Across the SELECT phase 3 studies, upadacitinib met all primary and ranked secondary endpoints. The primary endpoints include: In SELECT-EARLY, 52 percent of MTX-naïve patients treated with the drug 15 mg achieved ACR50 vs 28 percent treated with MTX at week 12
In SELECT-MONOTHERAPY, 68 percent of MTX-IR patients treated with upadacitinib 15 mg achieved ACR20 vs 41 percent treated with continued MTX at week 14 In SELECT-COMPARE, 71 percent of MTX-IR patients treated with upadacitinib 15 mg plus MTX achieved ACR20 vs 36 percent treated with placebo plus MTX at week 12.
In SELECT-NEXT, 64 percent of csDMARD-IR patients treated with upadacitinib 15 mg plus csDMARDs achieved ACR20 vs 36 percent treated with placebo plus csDMARDs at week 12.
In SELECT-BEYOND, 65 percent of biologic-IR patients treated with upadacitinib 15 mg plus csDMARDs achieved ACR20 vs 28 percent treated with placebo plus csDMARDs at week 12.
Patients taking upadacitinib achieved clinical remission, a state characterized by almost no disease activity and symptoms, even without methotrexate. Approximately 30 percent of patients treated with upadacitinib achieved clinical remission (as assessed by DAS28-CRP<2.6) at week 12 in SELECT-COMPARE and week 14 in SELECT-MONOTHERAPY compared to six percent with placebo plus methotrexate and eight percent with methotrexate, respectively. In SELECT-EARLY, 36 percent of patients achieved clinical remission (as assessed by DAS28-CRP<2.6) at week 12 compared to 14 per cent with methotrexate.
Durable remission rates were observed up to week 26. Forty-eight percent of patients treated with upadacitinib alone in SELECT-EARLY and 41 percent of patients treated with upadacitinib plus methotrexate in SELECT-COMPARE achieved clinical remission at weeks 24 and 26, compared to nine percent with placebo plus methotrexate and 18 percent with methotrexate, respectively. Analysis at weeks 24 and 26 were not controlled for multiple comparisons.
Upadacitinib significantly inhibited radiographic progression as measured by the change in modified total Sharp score (mTSS) from baseline compared to methotrexate in SELECT-EARLY (0.14 vs 0.67) and upadacitinib plus methotrexate compared to placebo plus methotrexate in SELECT-COMPARE (0.15 vs 0.78) through weeks 24 and 26, respectively.
Upadacitinib is under review by the European Medicines Agency (EMA), as well as regulatory authorities in Canada and Japan.
The drug is expected to be available in the US in late August 2019, AbbVie said.