JAK Inhibitors for Alopecia Areata: Selectivity and Pivotal Trial Efficacy

In "JAK Inhibitors for Alopecia Areata: Selectivity and Pivotal Trial Efficacy," our expert reviews how the three approved agents differ and what their pivotal trials showed.

Dr. Ungar begins by reading the Case 1 follow-up: given the patient's time-sensitive goal, a JAK inhibitor is started. He then reviews the three FDA-approved treatments for severe alopecia areata, which are deuruxolitinib, ritlecitinib, and baricitinib. Their selectivity differs. Deuruxolitinib and baricitinib are JAK1 and JAK2 inhibitors, while ritlecitinib inhibits JAK3 and TEC. He notes that the clinical implications of these differences are still being worked out.

Before reviewing data, Dr. Ungar cautions against comparing results across trials. Designs, patient populations, investigators, and locations differ, and none of these agents has been tested head to head. The primary endpoint in these trials is typically a SALT score of 20 or less, meaning patients regrew the vast majority of their scalp hair.

In THRIVE-AA1 and THRIVE-AA2, about 30 percent and 33 percent of patients taking deuruxolitinib 8 mg twice daily reached this endpoint at week 24, versus less than 1 percent on placebo. In the ALLEGRO trial, 23 percent of patients on ritlecitinib 50 mg once daily reached it at week 24, compared with 2 percent on placebo.

The BRAVE-AA1 and BRAVE-AA2 trials of baricitinib are more complex. They tested two doses and assessed the endpoint at week 36. At 2 mg, about 23 percent responded in BRAVE-AA1 and roughly 20 percent in BRAVE-AA2, versus about 6 percent and 3 percent on placebo. At 4 mg, Dr. Ungar recalls responses of roughly 30 to 35 percent against 6 to 8 percent on placebo. He concludes that all three are very effective and offer real potential for regrowth.

In "Starting JAK Inhibitors for Alopecia Areata: Safety Counseling and Choosing an Agent," Dr. Ungar will share his clinical experience and explain how he approaches access, safety, and drug selection.