The US Food and Drug Administration (FDA) has approved baricitinib (Olumiant, Eli Lilly and Company and Incyte Corporation) 2-mg tablets for the treatment of moderately to severely active rheumatoid arthritis (RA) in adults who have not responded adequately to one or more tumor necrosis factor (TNF) inhibitor therapies

The agency declined to approve the 4-mg tablets, citing safety concerns. The drug's prescribing information will contain a boxed warning about the risk for serious infections, malignancies, and thrombosis.

The approval follows an April 24 meeting of the FDA's Arthritis Advisory Committee at which the panel voted 10 to 5 in favor of the risk-benefit profile for once-daily baricitinib 2-mg tablets but voted 5 to 10 to say the evidence was insufficient to approve the 4-mg dose.

"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," Elizabeth L. Perkins, MD, Rheumatology Care Center, Birmingham, Alabama, said in a company news release. "Olumiant is an important option for rheumatologists to help address these patients' unmet needs."

The FDA's decision was made after consideration of data from the RA-BEACON study, a randomized, double-blind, placebo-controlled study that randomly assigned 527 patients with RA to receive baricitinib 2 mg, baricitinib 4 mg, or placebo in addition to conventional disease-modifying antirheumatic drugs (DMARDs) they were currently taking. Patients in the study had demonstrated an inadequate response or intolerance to at least one TNF inhibitor therapy. Study participants could have undergone prior therapy with other biological DMARDs.

Results

Patients who received baricitinib experienced significantly higher American College of Rheumatology 20 (ACR20) response rates and gains in all individual ACR20 component scores at week 12. Rates of ACR20 response were significantly higher in those treated with baricitinib compared with those who received placebo at week 12 (49% of baricitinib-treated patients vs 27% of placebo-treated patients).

Patients who received baricitinib also experienced early symptom relief, as evidenced by improved ACR20 scores as early as week 1 compared with those in the placebo group. Physical function — evaluated with the Health Assessment Questionnaire Disability Index — was also significantly improved in those who received baricitinib.

Baricitinib should not be used in combination with other Janus Kinase inhibitors or DMARDs, or with strong immunosuppressants such as azathioprine and cyclosporine. Baricitinib may be used alone or in combination with methotrexate or other nonbiologic DMARDs.

"We are pleased to provide RA patients in the U.S. an effective treatment option with Olumiant, as people with RA who have had an inadequate response to TNF inhibitors are generally considered to be some of the most difficult to treat RA patients," Christi Shaw, president, Lilly Bio-Medicines, said in the news release.

The companies have agreed to evaluate the long-term safety of baricitinib in those with rheumatoid arthritis with a randomized controlled clinical trial as part of the FDA's approval.

Patients taking baricitinib can develop gastrointestinal perforations and laboratory abnormalities including neutropenia, lymphopenia, anemia, liver enzyme elevations, and lip elevations. Patients taking baricitinib should not receive live vaccines.

The most frequent adverse events (occurring in at least 1% of those who received baricitinib in placebo-controlled trials) included upper respiratory tract infections, nausea, herpes simplex, and herpes zoster.

"Despite the advancements we've seen in the RA treatment landscape over the past several decades, many patients are still failing to achieve their disease management goals," Seth Ginsberg, co-founder and president of CreakyJoints and the Global Healthy Living Foundation, said in the news release.

"As it's important for RA patients to have multiple treatment options available to best suit their disease characteristics and experiences, the approval of Olumiant is very encouraging for our community."