JAK Inhibitor Baricitinib Under Study for RA

Patients with active rheumatoid arthritis that is resistant to standard-of-care treatments with synthetic or conventional DMARDs, can benefit from selective Janus kinase (JAK) 1 and 2 inhibitors when paired with once-daily baricitinib, a study shows.

In a study, designed to test baricitinib safety and efficacy, from Stanford University Medical Center published in the March 31 New England Journal of Medicine issue, researchers found patients experience the largest reduction in rheumatoid arthritis symptoms with a 4mg daily baricitinib dose. Symptoms also decreased with a 2 mg daily dose.

“These results provide evidence that selective inhibition of JAK1 and JAK2 with once-daily baricitinib has clinical efficacy in patients with active rheumatoid arthritis that is refractory to aggressive standard-of-care treatment with both conventional synthetic DMARDs and biologic DMARDs,” the authors wrote.

In this phase III, 24-week trial with 527 patients, investigators divided participants into three groups:  a 4 mg baricitinib group, a 2 mg barcitinib group, and a placebo group. At 12 weeks, patients were tested for the American College of Rheumatology 20 percent (ACR20) response, the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score, 28-Joint Disease Activity Score based on C-reactive protein level (DAS28-CRP), and Simplified Disease Activity Index (SDAI) Score of 3.3 or less.  [[{"type":"media","view_mode":"media_crop","fid":"47681","attributes":{"alt":"©Lilly","class":"media-image media-image-right","id":"media_crop_5495401176657","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"5640","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.008px; line-height: 1.538em; float: right;","title":"©Lilly","typeof":"foaf:Image"}}]]

At 12 weeks, more participants receiving 4 mg than the placebo had an ACR20 response - 55 percent and 27 percent, respectively. The same patient group also saw significant improvement in DAS28-CRP and HAQ-DI scores. There was no significant difference in SDAI scores for 2 mg and placebo groups.

Higher levels of adverse effects, such as withdrawal, cancer or cardiovascular events, appeared throughout the 24 weeks for both the 2 mg and 4 mg groups rather than the placebo. Among the 2 mg, 4 mg, and placebo groups, the rates were 71 percent, 77 percent, and 64 percent, respectively. Infections occurred in 44 percent, 40 percent, and 31 percent of cases. Serious events occurred in 4 percent, 10 percent, and 7 percent of patients, respectively.

According to study authors, results revealed rheumatoid arthritis patients with active disease and inadequate DMARD responses see the most clinical improvement from 4 mg baricitinib daily doses after 12 weeks. Additional studies are necessary, however, to determine long-term safety and response durability.

Disclosures:

The study supported by Eli Lilly and Incyte. It was designed by the sponsor, Eli Lilly. 

References:

Mark C. Genovese, M.D., Joel Kremer, M.D., et. al. "Baricitinib in Patients with Refractory Rheumatoid Arthritis," New England Journal of Medicine. March 31, 2016. N Engl J Med 2016;374:1243-52. DOI: 10.1056/NEJMoa1507247