WASHINGTON -- The FDA has approved the oral JAK inhibitor baricitinib (Olumiant) in a once-daily 2 mg dose for the treatment of moderately to severely active rheumatoid arthritis (RA) in patients who have had an inadequate response to at least one tumor necrosis factor (TNF) inhibitor, Eli Lilly and Incyte announced today.
Baricitinib has faced obstacles on its road to approval. In April 2017, the FDA rejected the application, citing concerns about safety and dosing. The original application had favored a 4 mg daily dose, with 2 mg doses for some patients. In a meeting of the FDA's Arthritis Advisory Committee in April of this year, the revised application focused on a 2 mg daily dose, with the possibility of 4 mg for patients who have had an inadequate response to two or more disease-modifying anti-rheumatic drugs.
Despite the widening array of available RA treatments, some patients still do not respond. "In my clinical practice, I continue to see patients who experience debilitating symptoms and who are waiting for a medicine that may be right for them," said Elizabeth L. Perkins, MD, of the Rheumatology Care Center in Birmingham, Alabama, in a press release. "Olumiant is an important option for rheumatologists to help address these patients' unmet needs."
The drug is currently available in more than 40 countries in the 2 mg and 4 mg daily doses. "What we've done this time is to incorporate feedback to show what populations specifically had the highest benefit-risk ratio," said Christi Shaw, president of Lilly Bio-Medicines. "So if you look at the data where patients have tried multiple other therapies and failed, those are the patients who responded best to 4 mg. We're trying to give options to both patients and physicians," Shaw told ڴŮ before the April meeting.
But the advisory committee remained concerned about safety, particularly because of thrombotic events. For the 2 mg dose, the committee vote at the April 2018 meeting regarding safety was nine in favor and six opposed for the 2 mg dose and five in favor and 10 opposed for the 4 mg dose.
Efficacy has been more clear cut. In the randomized placebo-controlled RA-BEACON study of 527 patients, significantly higher rates of 20% improvements on the criteria of the American College of Rheumatology 20% (ACR20) were seen at week 12 for patients receiving baricitinib compared with those given placebo (49% versus 27%). Significant improvements also were seen in physical function, and benefits were seen as early as week 1.
The drug's labeling will include a boxed warning stating the risks of serious infections, malignancies, and thrombosis.