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JAK Inhibitor Baricitinib Shows Promise in Moderate-to-Severe Rheumatoid Arthritis

First of several phase III trials to report results

A phase III study of the investigational medication baricitinib (Eli Lilly/Incyte Corporation) has met its primary endpoint of a higher American College of Rheumatology 20% improvement criteria (ACR20) response rate compared with placebo after 12 weeks of treatment. The study included patients with moderate-to-severe rheumatoid arthritis (RA) who previously failed treatment with one or more tumor necrosis factor (TNF) inhibitors and who were taking stable doses of conventional disease-modifying antirheumatic drugs (DMARDs).

Baricitinib is a once-daily, oral, selective Janus kinase-1 (JAK1) and JAK2 inhibitor. Four JAK enzymes have been identified: JAK1, JAK2, JAK3, and TYK2. JAK-dependent cytokines have been implicated in the pathogenesis of several inflammatory and autoimmune diseases, suggesting that JAK inhibitors may be useful for the treatment of a broad range of inflammatory conditions. Baricitinib demonstrated approximately 100-fold greater potency of inhibition against JAK1 and JAK2 than against JAK3 in kinase assays.

The RA-BEACON trial enrolled 527 patients who had previously failed at least one anti-TNF therapy, and included a high percentage of patients who had also received prior treatment with one or several non–anti-TNF biologic agents. The patients received once-daily baricitinib or placebo in addition to their background DMARD therapy.

The incidence of serious adverse events (AEs) associated with baricitinib treatment, including serious infections, was similar to that of placebo. No opportunistic infections or gastrointestinal perforations were observed. The baricitinib group had a higher incidence of treatment-emergent AEs compared with the placebo group. The most common AEs observed with baricitinib included headache, upper respiratory tract infection, and nasopharyngitis. Discontinuation rates due to AEs were similar between treatment groups.

Detailed data from this study will be reported in 2015. Meanwhile, the safety and efficacy of baricitinib are being evaluated in an extensive phase III program with a total enrollment of more than 3,000 patients with RA. In addition, baricitinib is in phase II development for the treatment of psoriasis and diabetic nephropathy.

It has been estimated that more than 23 million people worldwide have RA. Approximately three times as many women as men have the disease. Current therapies include nonsteroidal anti-inflammatory drugs (NSAIDs); oral DMARDs, such as methotrexate; and injectable biologic-response modifiers that target selected mediators implicated in the pathogenesis of RA.

Source: Eli Lilly; December 9, 2014.


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