Baricitinib vs. Placebo or Adalimumab for Rheumatoid Arthritis

Compared to placebo and adalimumab, the addition of once-daily oral baricitinib produced significant clinical improvements in rheumatoid arthritis patients with inadequate response to methotrexate, a new study finds.

The study appears in the February 16 issue of the New England Journal of Medicine. 

This 52-week study was a phase 3, randomized, double-blinded, placebo-controlled trial of 1,307 patients with active rheumatoid arthritis, aged 18 and over, receiving background methotrexate therapy. Patients were recruited from 281 centers in 26 countries and randomly assigned in a 3:3:2 ratio to receive a placebo, 4 mg of baricitinib once daily, or 40 mg of subcutaneous adalimumab every other week in addition to existing background therapy including, but not limited to methotrexate.  

Led by Peter Taylor, M.D., Ph.D., from the University of Oxford in the United Kingdom, the goal of the study was to evaluate a regimen of 4 mg of baricitinib once daily was compared with placebo or 40 mg of adalimumab in patients who had previously responded inadequately to methotrexate and had not been treated with biologic disease-modifying antirheumatic drugs. The primary outcome was a 20 percent improvement based on criteria from the American College of Rheumatology, also known as the ACR20 response. Secondary outcomes included overall disease activity, disability, patient-reported outcomes, and radiographic progression of joint damage. 

For the primary outcome, baricitinib demonstrated greater clinical benefits at 12 weeks than the placebo group (70 vs. 40 percent, P<0.001) as well as greater efficacy than adalimumabin for ACR20 response rate (70 vs. 61 percent%, P=0.014). Regarding secondary outcomes, all objectives were met.

“In patients with active rheumatoid arthritis despite receiving therapy with methotrexate, the addition of once-daily oral baricitinib was associated with improvements in signs and symptoms, physical function, patient-reported outcomes, and progression of structural joint damage as compared with placebo and with improvements in ACR20 response and DAS28-CRP as compared with adalimumab,” wrote Taylor and colleagues.

Rheumatoid arthritis is often treated with synthetic disease-modifying antirheumatic drugs like methotrexate. More recently, clinical remission of rheumatoid arthritis appears within reach through increased use of biologic disease-modifying antirheumatic drugs that target tumor necrosis factor (TNF). 

In particular, activated Janus kinases play a key role in the relationship between intracellular signaling from cell-surface receptors and the cytokines utilized in the pathologic processes of rheumatoid arthritis. To date, clinical trials of baricitinib have shown that the drug provides reversible inhibition of Janus kinases and that it is efficacious in studies that have involved patients with rheumatoid arthritis. 

“Our study showed that for the outcome measure used as the primary end point, the combination of baricitinib plus methotrexate was superior to adalimumab plus methotrexate, the latter being a current standard-of-care treatment in this patient population,” wrote Taylor and colleagues.

See the related story:  "A Clinical Update on Baricitinib for Rheumatoid Arthritis"

Disclosures:

This research was funded by Eli Lilly and Incyte. 

References:

Peter C. Taylor, Edward C. Keystone, Désirée van der Heijde, et al. “Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis,” New England Journal of Medicine. Published February 16, 2017. DOI: 10.1056/NEJMoa1608345.