The JAK inhibitor deuruxolitinib showed efficacy and safety among patients with alopecia areata in phase 3 trials and was subsequently approved by the FDA. The approved dosing is 8 mg twice daily, which showed efficacy in the phase 2 dose-ranging study. This phase 2 dose-optimization study, conducted by Brett King, MD, PhD, Dermatology Physicians of Connecticut, Fairfield, Connecticut, and colleagues, compared the efficacy and safety of 8 mg deuruxolitinib twice daily with 16 mg deuruxolitinib once daily.
This study enrolled 57 patients with severe alopecia areata who were randomly assigned 1:1 to receive either 8 mg deuruxolitinib twice daily (n = 29) or 16 mg deuruxolitinib once daily (n = 28) for 24 weeks. Randomization was stratified by three alopecia areata subtypes: patchy type hair loss, complete hair loss on the scalp with or without body hair loss, or limited, band-like hair loss. SALT score was assessed at screening, baseline, and for every 4 weeks until Week 24. The primary end point was relative change in SALT score from baseline.
After a follow-up duration of 24 weeks, the mean relative change in SALT score from baseline was 46.4 among patients who received 8 mg deuruxolitinib twice daily compared to 18.0 with those who received 16 mg once daily. The mean relative change in SALT score from baseline over time was also higher in the 8 mg twice daily arm than the 16 mg once daily arm. The proportion of patients who achieved a SALT score of less than or equal to 20 and less than or equal to 10 over time was 34.5% and 20.7%, respectively, in the 8 mg twice daily arm compared to 10.7% and 3.6% in the 16 mg once daily arm at week 24.
Of the total treatment-emergent adverse events reported, 29 events in 12 patients in the 8 mg twice daily arm and 13 in 14 patients in the 16 mg once daily arm were considered related or possibly related to deuruxolitinib. No treatment-emergent adverse events of special interest (serious infections, malignancy, major adverse cardiovascular events, or thrombosis) occurred in either arm. There was one treatment-emergent adverse event (increased blood creatinine) which led to drug interruption, with the patient continuing on the study after resolution. There were no reported serious treatment-emergent adverse events, or drug discontinuations caused by treatment-emergent adverse events, or deaths.
Dr. King and colleagues concluded, “Across all endpoints, BID [twice daily] dosing of deuruxolitinib was associated with greater scalp hair regrowth compared with QD [once daily] dosing.” They added that this study “not only shows that BID dosing is necessary to optimize the efficacy of deuruxolitinib, but that hair growth is dependent on all-day exposure to deuruxolitinib (ie that pharmacokinetics and pharmacodynamics are linked, which likely informs the treatment of AA in general.)”