The FDA approved upadacitinib (Rinvoq, AbbVie), a 15-mg, once-daily oral Janus kinase inhibitor, for the treatment of adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to methotrexate.

The approval is supported by data from the SELECT program, one of the largest registrational phase 3 clinical programs 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 patients with RA, including those who failed or were intolerant to biologic disease-modifying antirheumatic drugs and who were naive or inadequate responders to methotrexate. Upadacitinib is not indicated for methotrexate-naive patients.

“Despite the availability of multiple treatment options with varying mechanisms of action, many patients still do not achieve clinical remission or low disease activity—the primary treatment goals for rheumatoid arthritis,” said Roy M. Fleischmann, M.D., primary investigator for SELECT-COMPARE and clinical professor at the University of Texas Southwestern Medical Center at Dallas. “With this FDA approval, RINVOQ has the potential to help additional people living with RA achieve remission who have not yet reached this goal.”

Across the SELECT Phase 3 studies, RINVOQ met all primary and ranked secondary endpoints. The primary endpoints include:

• In SELECT-EARLY, 52 percent of MTX-naïve patients treated with RINVOQ 15 mg achieved ACR50 vs 28 percent treated with MTX at week 12¹
• In SELECT-MONOTHERAPY, 68 percent of MTX-IR patients treated with RINVOQ 15 mg achieved ACR20 vs 41 percent treated with continued MTX at week 14¹
• In SELECT-COMPARE, 71 percent of MTX-IR patients treated with RINVOQ 15 mg plus MTX achieved ACR20 vs 36 percent treated with placebo plus MTX at week 12¹
• In SELECT-NEXT, 64 percent of csDMARD-IR patients treated with RINVOQ 15 mg plus csDMARDs achieved ACR20 vs 36 percent treated with placebo plus csDMARDs at week 12¹
• In SELECT-BEYOND, 65 percent of biologic-IR patients treated with RINVOQ 15 mg plus csDMARDs achieved ACR20 vs 28 percent treated with placebo plus csDMARDs at week 12¹

“The discovery and development of RINVOQ is indicative of AbbVie’s long-standing commitment to advancing the science for people living with immune-mediated conditions,” said Michael Severino, M.D., vice chairman and president, AbbVie. “Today’s FDA approval marks an important milestone in our pursuit to deliver innovative medicines that advance care for people living with rheumatoid arthritis.”

Clinical Remission
Patients taking RINVOQ achieved clinical remission, a state characterized by almost no disease activity and symptoms, even without methotrexate.^2–3,6Approximately 30 percent of patients treated with RINVOQ 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.¹ In SELECT-EARLY, 36 percent of patients treated with RINVOQ achieved clinical remission (as assessed by DAS28-CRP<2.6) at week 12 compared to 14 percent with methotrexate.¹ 

Durable remission rates were observed up to week 26. Forty-eight percent of patients treated with RINVOQ alone in SELECT-EARLY and 41 percent of patients treated with RINVOQ 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.¹ Analysis at weeks 24 and 26 were not controlled for multiple comparisons.^3,10

Radiographic Inhibition
RINVOQ 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 RINVOQ plus methotrexate compared to placebo plus methotrexate in SELECT-COMPARE (0.15 vs 0.78) through weeks 24 and 26, respectively.¹

Ease of Use and Access
Designed to help accommodate the physical limitations of people living with RA, the packaging for RINVOQ includes a bottle cap with a wide, easy-to-grip texture and an embedded tool that punctures the foil liner to simplify medication access. This packaging design was awarded the Arthritis Foundation Ease of Use Commendation.

“Rheumatoid arthritis can have a debilitating impact on the lives of those with the chronic disease, including making it difficult to perform everyday tasks,” said Cindy McDaniel, senior vice president, consumer health, Arthritis Foundation. “The Arthritis Foundation is committed to recognizing innovation that can help patients living with rheumatoid arthritis and we are proud to recognize AbbVie with our Ease of Use Commendation for the packaging design of RINVOQ.”

Across the SELECT phase 3 studies, upadacitinib met all primary and ranked secondary end points. The most common side effects included upper respiratory tract infections (common cold, sinus infections), nausea, cough and pyrexia.