Baricitinib Effective for Treating Refractory Rheumatoid Arthritis

Unlike many other studies that have evaluated biologics largely in patients with RA who are naive to biologics or failed first-line treatment, such as those with early disease, he stresses the study by Genovese and colleagues is unique in that it evaluates efficacy of a new agent in a difficult-to-treat population. “We lack good interventional randomized controlled trials involving these challenging patients,” he says.

Oral JAKs

Baricitinib is the second drug in the relatively new class of drugs called oral Janus kinase (JAK) 1 and 2 inhibitors. The first drug in this class, tofacitinib, was approved by the Food and Drug Administration (FDA) in May 2012 for RRA patients.

Saying he currently uses tofacitinib for his RRA patients, Dr. Paz says the potential availability of baricitinib will provide an additional treatment option from the JAK-inhibitor class of agents for patients who do not respond well to tofacitinib. “This would be similar to the current strategy of exchanging between biologics from the same class, [such as] TNF inhibitors, to find the right match for our patients,” he says.

Dr. Genovese

Currently, baricitinib is under regulatory review by the FDA for treatment of inflammatory and autoimmune diseases. According to a press release by the manufacturer of the drug, four Phase 3 clinical trials of the drug have been conducted to “support regulatory submission in most countries.”²

“Hopefully, [these results] will translate to a commercially approved therapy to help patients with active disease,” said Dr. Genovese.

Safety

One big concern raised by the study is the adverse events reported with baricitinib, says Dr. Paz. Both groups of patients receiving baricitinib at the 2 mg and 4 mg doses had higher rates of adverse events than the placebo group (71% and 77% vs. 64%, respectively), including higher rates of infections (44% and 40% vs. 31%, respectively). Headache, upper respiratory infections and nasopharyngitis were the most common adverse events in the patients treated with baricitinib. None of the patients had opportunistic infections, tuberculosis or gastrointestinal perforations.

Rates of serious adverse events were highest in the 4 mg baricitinib group followed by the placebo group, with the fewest in the 2 mg baricitinib group (10%, 7% and 4%, respectively). In the 4 mg group, the serious adverse events included two nonmelanoma skin cancers and two major adverse cardiovascular events, which included a fatal stroke.

Emphasizing that the adverse events reported in the study are high, Dr. Paz points out the high rate of serious adverse events in the placebo group indicates the need to ask why this patient population had such a high rate of adverse events.