Together with Xeljanz (tofacitinib), Olumiant represents a new class of RA treatments known as JAK inhibitors.
Janus kinase inhibitors
There are four known Janus kinase (JAK) enzymes. Baricitinib is a reversible inhibitor of JAK1 and JAK2, which are widely expressed and mediate signalling of multiple cytokines implicated in the pathogenesis of RA, including interleukin-6, granulocyte-macrophage colony-stimulating factor and interferons.
Phase III trials
Phase III trials of baricitinib comprised four completed studies in a range of adults with RA, from treatment-naïve to inadequate responders to TNF inhibitors. Results showed significant improvements in the signs and symptoms of RA in patients who received baricitinib compared with those who received standard of care therapies such as methotrexate and adalimumab.
RA-BEGIN compared baricitinib, as monotherapy or combined with methotrexate, with methotrexate monotherapy in 588 RA patients. Baricitinib monotherapy was superior to methotrexate monotherapy at week 24, with a higher ACR20 response rate (77% vs 62%, p≤0.01). Similar results were observed for combination therapy.
RA-BEAM was a placebo- and adalimumab-controlled trial of baricitinib plus methotrexate in 1307 RA patients with an inadequate response to methotrexate. Baricitinib showed greater clinical benefits than placebo or adalimumab at week 12, according to ACR20 response rate.
RA-BUILD was a placebo-controlled 24-week study in 684 RA patients with an inadequate response or intolerance to one or more conventional DMARDs. More patients achieved an ACR20 response at week 12 with baricitinib 4mg than placebo. Compared with placebo, statistically significant improvements in Disease Activity Score (DAS28), Simplified Disease Activity Index (SDAI) remission, Health Assessment Questionnaire-Disability Index, morning joint stiffness, worst joint pain and worst tiredness were also observed.
RA-BEACON study was a placebo-controlled trial of baricitinib in 527 RA patients with an inadequate response to biologic DMARDs. Treatment with baricitinib 4mg significantly improved most outcomes at 12 weeks compared with placebo.
The most frequent adverse events seen with baricitinib during trials were increases in LDL-cholesterol, upper respiratory tract infections and nausea. The risks and benefits of treatment should be carefully considered before initiating therapy in patients with active, chronic or recurrent infections. Lipids should be assessed 12 weeks after starting treatment.