Baricitinib Benefits Refractory RA & Gets a Second Look by the FDA
Baricitinib, a novel orally administered drug, appears effective for patients with highly refractory rheumatoid arthritis (RA). Baricitnib belongs to a new class of drugs being evaluated in RA called JAK-1/2 inhibitors. In July 2017 the FDA expressed concerns about safety, especially an “imbalance in thromboembolic events” only seen with the 4 mg dose observed in early RA clinical trials
Researchers originally reported in the March 31 issue of the New England Journal of Medicine that baricitinib produced a 55% response in a cohort of 527 patients with refractory rheumatoid arthritis, compared with 27% of those given a placebo.1
The mean age of study participants was 56, average disease duration was 14 years, and 80% were women. They had moderate to severely active disease, with baseline swollen and tender joint counts of 17 and 29, respectively. Each participant had undergone one to several previous conventional therapies and/or biologic agents.
Participants were treated with either 2 mg or 4 mg of baricitinib each day or a placebo, plus conventional therapies including DMARDs, nonsteroidal anti-inflammatory drugs, and 10 mg prednisone or less per day and directly compared.
In addition to the improved response rate, patients receiving the 4-mg dose of baricitinib also had significantly greater improvements in the disease activity score in 28 joints at week 12 and for a Health Assessment Questionnaire Disability Index.
These results are consistent with two previous clinical studies demonstrating significant improvements of barciitinib in individuals with refractory RA.2,3. In August 2017 FDA elected to allow a revised New Drug Application (NDA) for baricitinib before the end of January 2018. The resubmission package will include new safety and effectiveness information.
- Genovese M, Kremer J, Samani O, et al. Barcitinib in patients with refractory rheumatoid arthritis. New England Journal of Medicine. March 31, 2016. DOI: 10.1056/NEJMoa1507247
- Fleischmann R, et al. Baricitinib, Methotrexate, or baricitinib plus methotrexate in patients with early rheumatoid arthritis who had received limited or no treatment with disease modifying anti-rheumatic drugs: Phase III Trial Results. American College of Rheumatology 2015. Abstract 1045.
- Taylor P, et al “Baricitinib versus placebo or adalimumab in patients with active rheumatoid arthritis and an inadequate response to background methotrexate therapy: results of a phase 3 study” ACR 2015; Abstract 2L.