JAK Inhibitors: Looking at Selectivity and Safety

Tofacitinib—a Janus Kinase (JAK) inhibitor indicated for the treatment of rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis—carries a black box warning cautioning risk for malignancies, serious infection, and thromboembolism.

Despite the concerning label, dermatologists should not approach these drugs with trepidation and alarm, noted Brett King, MD, PhD, of Yale School of Medicine.

He urged his colleagues to view these risks in the context of the clinical trials in which the drug was evaluated.

“Everybody needs to understand [that] rheumatoid arthritis clinical trials almost always involved concomitant methotrexate,” King said. Even more, many of these patients were also likely to take prednisone.

The relationship of tofacitinib’s safety profile in RA populations to JAK inhibitors in patients with dermatologic conditions should be understood in that fuller context.

King indicated that the summary data can truly provide a clearer picture of the JAK inhibitor’s safety and tolerability among dermatology patients, particularly within clinical trials. Such data may illuminate the kinds of patients at risk for more serious adverse events.

He expressed a similar sentiment of patience regarding trying to understand and compare selectivity across JAKs and disease states.

“We need to understand what the entirety of the data says to know how to think about using them in any patient population,” King said.

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