Baricitinib, Oral Janus Kinase Inhibitor in Patients with Active RA who have an Inadequate Response to TNF Inhibitors.
Baricitinib is an oral reversible inhibitor of JAK 1 and 2. Marc Genovese presented a trial designed to assess the safety and efficacy of baricitinib in patients who were failing DMARDs and had tried other DMARDs and TNF-inhibitors.
Patients were randomized to baricitinib 2 mg QD, 4 mg QD or placebo with a primary outcome measure of the ACR 20 at week 12. Patients were mostly females (80%), average age of 55, 75% were ACPA- or RF-positive and patients had about 18 swollen joints. The patients were allowed to receive non-biologic DMARDs throughout the study.
The study met its primary endpoint with an ACR 20 of 55% at week 12 and 46% at week 24. The most interesting thing was that the ACR 20 at week 12 was 64% if a patient had failed a single TNF inhibitor and 53% if a patient had failed 3 biologic DMARDs. Even more interesting, the delta versus placebo for those who failed a single biologic was 32% and 40% if a patient had failed 3 biologics. There was a dose-dependent improvement in both DAS and CDAI.
A higher rate of serious adverse events was seen in the 4 mg dose group. There was no increase in serious infections, however, there was an increase in Zoster that was dose-related.
In conclusion, baricitinib appears to be an effective therapy with the benefits beginning as early as 1 week after treatment initiation. Significant improvements in signs and symptoms were sustained through 24 weeks of treatment. The safety and tolerability remained satisfactory. The greatest benefits were seen with a dose of 4 mg QD.