Baricitinib review shows efficacy, safety in severe alopecia areata

Key takeaways:

• Baricitinib is FDA-approved as the first and only treatment of severe alopecia areata in adults.
• Baricitinib is considered efficacious and “relatively tolerable” based on the phase 3 BRAVE trials.

In a literature review evaluating the findings of two identical phase 3 trials of baricitinib, the oral Janus kinase 1/2 inhibitor was found to be efficacious, safe and “relatively tolerable” in the treatment of severe alopecia areata.

As the first and only FDA-approved treatment for adults with severe AA, Rohan Singh, BS, and Marcia S. Driscoll, MD, PharmD, both of the University of Maryland School of Medicine, used the Medline (PubMed) and Embase databases to assess baricitinib’s efficacy and safety for the treatment of AA. They identified two phase 3 trials for their review.

“The objective of this review is to assess the mechanism of action, pharmacokinetics, pharmacodynamics, efficacy and safety of baricitinib in the treatment of AA,” Singh and Driscoll wrote.

Efficacy

The two randomized, double-blinded, parallel group, placebo-controlled phase 3 trials, BRAVE-AA1 and BRAVE-AA2, evaluated the safety and efficacy of baricitinib in adults with severe AA.

At baseline, all patients had a Severity of Alopecia Tool score of 50 or greater, meaning each had at least 50% scalp hair loss.

In BRAVE-AA1 and BRAVE-AA2, 598 and 490 patients, respectively, were randomly assigned to receive oral baricitinib 4 mg, baricitinib 2 mg or placebo once daily for 36 weeks.

In both trials, up to 38.8% of patients treated with 4 mg of baricitinib achieved less than 20% scalp hair loss by week 36. For those treated with 2 mg, up to 22.8% also achieved less than 20% hair loss, whereas only up to 6.2% of the placebo group reached the same goal.

More patients treated with 4 mg in the first and second trials (35.2% and 38.9%, respectively) achieved Clinician-Reported Outcome (CRO) success compared with placebo (4.4% and 5.5%; P < .001 for both).

On the other hand, while those treated with 2 mg in BRAVE-AA1 achieved higher CRO success than placebo-treated patients, the difference was not significant in BRAVE-AA2. Overall, those treated with 4 mg achieved clinically better outcomes than those treated with 2 mg or placebo.

Safety

JAK inhibitors are known for their potentially serious adverse events, according to the authors. Baricitinib comes with black-box warnings which include risk for malignancy, major adverse cardiovascular events (MACE), thrombosis, serious infections and mortality.

However, during the BRAVE trials, no deaths occurred, and most adverse events were mild to moderate in nature.

Across all dosages in both trials, up to 7.7% of patients contracted an upper respiratory infection. Also, up to 9% experienced headaches, 7.5% nasopharyngitis, 5.8% acne and 7.7% urinary tract infection. Up to 37.4% of patients contracted one or more of these infections.

As far as serious adverse events go, one case of MACE, one malignancy and three cases of serious infections occurred in both baricitinib groups, whereas only one malignancy occurred in the placebo group.

Conclusion

Singh and Driscoll concluded that JAK inhibitors are a class of promising new therapeutics for the treatment of AA. Baricitinib in particular is deemed efficacious and “relatively tolerable” in spite of the numerous black-box warnings associated with the drug, according to the authors.

“Although baricitinib is associated with multiple black-box warnings, it may serve as a useful therapeutic alternative in patients with treatment-resistant, longstanding, severe or extensive AA,” the authors wrote.