A phase 3 clinical trial has shown that once-daily oral baricitinib significantly improved daily physical functioning and substantially reduced symptoms in patients with refractory rheumatoid arthritis (RA), according to a study published online March 31, 2016 in the New England Journal of Medicine.
“This is the first drug to demonstrate meaningful clinical benefit in patients who’ve failed virtually every other commercial drug for rheumatoid arthritis,” said the study’s lead author Mark Genovese, MD, professor of immunology and rheumatology at Stanford University School of Medicine in Palo Alto, CA.
Baricitinib, available in pill form, belongs to the category of small-molecule Janus-kinase (JAK) inhibitors. It proved effective in phase 2 clinical trials of patients with RA who no longer responded to conventional rheumatoid arthritis therapy such as methotrexate and other synthetic disease-modifying antirheumatic drugs (DMARDs).
“Despite the ... lack of success with a series of other established therapies, almost 10% of the patients [on baricitinib] went into full remission—that is, a cure-like state on the drug—within 6 months, and almost half of the patients demonstrated significant improvement in disease activity and physical functioning,” said senior author Joseph Smolen, MD, Manager of the University Clinic for Internal Medicine III at the Medical University of Vienna, in Austria.
“All this may constitute a new basis for the treatment of rheumatoid arthritis that could become available in the near future,” Dr. Smolen added.
This trial was conducted in 178 centers in 24 countries and involved 527 patients with severe RA that affected at least 6 joints. All patients had failed at least one tumor necrosis factor (TNF) inhibitor or biologic DMARD, and many had failed two or more.
Researchers randomly assigned patients to one of three treatment groups: 2 mg of baricitinib, 4 mg of baricitinib, or placebo. After 24 weeks of treatment, about 55% of patients taking the 4 mg dose of baricitinib had a reduction of at least 20% in the number of affected joints at week 12, as assessed by the American College of Rheumatology 20% (ACR20) improvement criteria.
For patients on the 2 mg dose, 49% had a similar reduction. By comparison, only 27% of the patients in the placebo group achieved this effect.
Patients on either the 2 mg or the 4 mg dose of baricitinib also had improved physical function and reductions in markers of inflammation, both in absolute terms and in comparison with placebo, the researchers found. These improvements largely remained at 24 weeks, Dr. Genovese said.
“The drug worked well across all patient subgroups, independently of what they’d been taking before or how long they’d had the disease,” he added.
Another advantage for patients is that baricitinib comes in a pill. Dr. Smolen noted: “The medication is taken orally once a day and does not have to be administered intravenously or subcutaneously with a needle, unlike other medication. This is significantly more comfortable for the affected people.”
Most adverse events included mild upper-respiratory infections and were more common among patients in the 4 mg group (77%) and 2 mg group (71%) compared to the placebo group (64%). Serious adverse events affected 10% of the high-dose group, 4% of the low-dose group, and 7% of the placebo group.
Eli Lilly, the manufacturer of baricitinib, funded the trial.