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

This new therapy is expected to be available in the United States later this month.

Designed to help accommodate people living with RA, AbbVie’s packaging for upadacitinib includes a bottle cap with a wide, easy-to-grip texture and an embedded tool that punctures the foil liner to simplify medication access.

"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, in a prepared statement.
 
The FDA’s approval of upadacitinib is supported by data from the SELECT program, a large registrational Phase 3 program in RA with approximately 4400 patients evaluated across all treatment arms in 5 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 antirheumatic drugs and who were naïve or inadequate responders to methotrexate.

"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, MD, primary investigator for SELECT-COMPARE and clinical professor at the University of Texas Southwestern Medical Center at Dallas, in a prepared statement. "With this FDA approval, (upadacitinib) 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% of MTX-naïve patients treated with upadacitinib 15 mg achieved ACR50 vs 28% treated with MTX at week 12
  • In SELECT-MONOTHERAPY, 68% of MTX-IR patients treated with upadacitinib 15 mg achieved ACR20 vs 41% treated with continued MTX at week 14
  • In SELECT-COMPARE, 71% of MTX-IR patients treated with upadacitinib 15 mg plus MTX achieved ACR20 vs 36% treated with placebo plus MTX at week 12
  • In SELECT-NEXT, 64% of csDMARD-IR patients treated with upadacitinib 15 mg plus csDMARDs achieved ACR20 vs 36% treated with placebo plus csDMARDs at week 12
  • In SELECT-BEYOND, 65% of biologic-IR patients treated with upadacitinib 15 mg plus csDMARDs achieved ACR20 vs 28% treated with placebo plus csDMARDs at week 12
The most common adverse effects associated with upadacitinib include upper respiratory tract infections, nausea, cough and pyrexia. Patients treated with upadacitinib are at increased risk for developing serious infections that may lead to hospitalization or death. These infections include tuberculosis (TB), invasive fungal, bacterial, viral, and other infections due to opportunistic pathogens.

Lymphoma and other malignancies have been observed in patients treated with upadacitinib. Thrombosis, including deep vein thrombosis, pulmonary embolism, and arterial thrombosis, have occurred in patients treated with JAK inhibitors used to treat inflammatory conditions. Patients treated with upadacitinib also may be at risk for other serious adverse reactions, including gastrointestinal perforations, neutropenia, lymphopenia, anemia, lipid elevations, liver enzyme elevations, and embryo-fetal toxicity.


Reference

AbbVie Receives FDA Approval of RINVOQ™ (upadacitinib), an Oral JAK Inhibitor For The Treatment of Moderate to Severe Rheumatoid Arthritis [news release]. North Chicago, IL; August 16, 2019: AbbVie website. https://news.abbvie.com/news/press-releases/abbvie-receives-fda-approval-rinvoq-upadacitinib-an-oral-jak-inhibitor-for-treatment-moderate-to-severe-rheumatoid-arthritis.htm. Accessed August 2019.