Phase 3 Clinical Trial Finds Drug, Baricitinib, of Benefit to Rheumatoid Arthritis Patients Who Failed at Other Treatments

Phase 3 Clinical Trial Finds Drug, Baricitinib, of Benefit to Rheumatoid Arthritis Patients Who Failed at Other Treatments

Results from an international Phase 3 trial evaluating baricitinib as an rheumatoid arthritis (RA) treatment in patients who failed at other therapies reported a significant reduction in symptoms and increased physical function. Trial results were described in a study, “Baricitinib in Patients with Refractory Rheumatoid Arthritis,” published in the New England Journal of Medicine.

Before the mid-1990s, more than 50 percent of RA patients were disabled within 20 years of diagnosis. Today, a number of medications are available to treat RA — including adalimumab, etanercept, and infliximab in the U.S., biologics that work by blocking the action of the tumor necrosis factor (TNF), a substance secreted by immune cells and thought to stimulate the immune response and accompanying inflammation. However, an estimated 15 percent to 20 percent of RA patients become refractory, meaning these drugs either no longer provide sufficient benefit or result in unacceptable side effects.

Baricitinib is a small-molecule oral drug — part of a category called Janus-kinase inhibitors — that works by interfering with the intracellular enzymes responsible for signaling activity that helps to set various inflammatory substances in motion.

“This is the first drug to demonstrate meaningful clinical benefit in patients who’ve failed virtually every other commercial drug for rheumatoid arthritis,” Mark Genovese, MD, professor of immunology and rheumatology at  Stanford University School of Medicine and the study’s lead author, said in a press release.

The Phase 3 trial study, sponsored by Eli Lilly and Co., involved 527 patients enrolled at 178 centers in 24 countries.  Patients had moderate to severe RA with at least six joints affected, and all had failed at using one or more anti-TNF biologic medications. Participants were randomly assigned to be treated once daily for 24 weeks with either 4 mg of baricitinib, 2 mg of baricitinib, or placebo.

Results showed that treatment decreased RA symptoms and prevented structural damage. In the high-dose group, about 55 percent of patients saw at least a 20 percent reduction in affected joints by at week 12, the study’s primary endpoint. A similar effect was recorded in 49 percent of those receiving baricitinib at the lower dose, and 27 percent of those on placebo.

Improvement also were reported in increased physical function and reduced inflammation in both baricitinib groups — both in absolute terms and compared to placebo — with improvements maintained for study’s 24 weeks. “The drug worked well across all patient subgroups, independently of what they’d been taking before or how long they’d had the disease,” Dr. Genovese added.

Side effects were mostly mild upper-respiratory infections, recorded in 77 percent of patients on high-dose baracitinib, 71 percent on low-dose, and 64 percent among those on placebo. Serious side effects were seen in 10 percent of patients on high-dose baricitinib, 4 percent on low dose, and 7 percent in the placebo group.

A number of patients also developed herpes zoster (shingles), a reactivation of the latent chicken-pox virus resulting from weakened immune systems: in the high-dose group at week 12, 2 percent, and 4 percent at 24 weeks; in the low-dose group, 1 percent each at weeks 12 and 24; and among those on placebo, 0.5 percent at 12 weeks and 1 percent at 24 weeks.


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