November 11, 2015 • By
Barcitinib Promising in Phase 3 Trials
Baricitinib, a once-daily oral selective JAK1 and JAK2 inhibitor, has shown positive results in the Phase 3 RA-BEAM study.1,2 This is the fourth successful Phase 3 study of this agent for treating adults with moderate to severe activerheumatoid arthritis (RA). This study enrolled more than 1,300 adults with active RA despite use of methotrexate (MTX). The safety and efficacy of baricitinib was compared with placebo for 24 weeks or adalimumab for 52 weeks. Patients receiving MTX were randomized to receive either 4 mg barcitinib once daily, 40 mg subcutaneous adalimumab every other week or placebo
Baricitinib was proved superior to placebo in ACR20 response after 12 weeks of treatment. In addition, baricitinib-treated patients showed improvement in the secondary endpoint of DAS28-hsCRP disease activity score after 12 weeks of treatment compared with adalimumab-treated patients. Baricitinib was also superior to placebo in preventing progressive radiographic structural joint damage after 24 weeks of treatment. This result was maintained through 52 weeks of therapy. Serious adverse events were similar between baricitinib and placebo, but lower for adalimumab; and serious infection rates were comparable across all groups. Treatment-emergent side effects, including infections, were greater for active treatment groups compared with placebo-treated patients. Discontinuations due to adverse events were similar across all treatment groups.
Prior baricitinib Phase 3 studies included RA-BEACON,3 for patients who failed at least one tumor necrosis factor inhibitor and were taking stable doses of conventional disease-modifying anti-rheumatic drugs (DMARDs); RA-BUILD, for patients who had either failed or could not tolerate treatment with at least one conventional DMARD; and RA-BEGIN, which compared barcitinib with MTX monotherapy.4
FDA Orders Drug-Interaction Studies for Kayexelate
The U.S. Food and Drug Administration (FDA) is requiring the manufacturer of sodium polystyrene sulfonate (Kayexalate), which is used to manage hyperkalemia, to conductdrug-interaction studies to determine if it decreases the absorption of other orally administered medications.5 Current labeling describes sodium polystyrene sulfonate as having the potential to decrease absorption of lithium and thyroxine; however, more extensive drug-interaction studies have not been undertaken.
This new request stems from the FDA’s approval of a new potassium-lowering drug, patiromer (Valtassa), which bound to about half of medications tested, potentially diminishing their therapeutic effects. To decrease these effects, it’s recommended that patiromer be administered with at least six hours’ separation from other orally administered medications. Because patiromer binds agents, it’s now thought that sodium polystyrene sulfonate may also bind these agents—hence the recommendation for new studies.
Michele B. Kaufman, PharmD, CGP, RPh, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.
- Incyte Corp. New release: Baricitinib demonstrates superiority to adalimumab in improving signs and symptoms of rheumatoid arthritis in pivotal phase 3 study. 2015 Oct 14.
- S. National Institutes of Health. A study in moderate to severe rheumatoid srthritis (RA-BEAM). ClinicalTrials.gov. 2015 May.
- Barber J. Eli Lilly, Incyte’s baricitinib hits main goal of Phase III rheumatoid arthritis study. FirstWord Pharma. 2014 Dec 9.
- Eli Lilly and Comp., Incyte Corp. New release: Baricitinib superior to methotrexate in reducing signs and symptoms in pivotal phase 3 study in patients with rheumatoid arthritis. 2015 Sep 29.
- U.S. Food and Drug Administration. Safety alerts for human medical products:Kayexalate (sodium polystyrene sulfonate): Drug safety communication—FDA requires drug interaction studies. 2015 Oct 22.