Sublingual tofacitinib for alopecia areata: a roll‐over pilot clinical trial and analysis of pharmacokinetics

Abstract Tofacitinib is a JAK1/3 inhibitor used off‐label to treat alopecia areata (AA). Oral tofacitinib undergoes extensive hepatic metabolism and has numerous drug interactions and a half‐life of 3 hours necessitating twice daily dosing. Sublingual delivery bypasses hepatic first‐pass metabolism, which may provide pharmacokinetic benefits and reduce gastrointestinal side effects. We investigate sublingual tofacitinib as a novel form of administration in a cohort of treatment‐resistant patients. The objective of this work is to assess the efficacy and pharmacokinetics of sublingual tofacitinib in moderate‐to‐severe AA patients. An open‐label, roll‐over pilot clinical trial was conducted. Participants were recruited from a preceding trial. All responders (≥50% reduction in Severity of Alopecia Tool [SALT] score, SALT50) in the preceding trial continued on the same treatment (cyclosporine/placebo), whereas nonresponders rolled over to receive open‐label sublingual tofacitinib 5 mg twice daily for 12 weeks. Treatment response as reduction in SALT score after 12 weeks (low: 15–29%, medium: 30–49%, good: 50–75%, and high grade: 75–100%) was measured. Pharmacokinetics was analyzed using liquid chromatography tandem mass spectrometry. Eighteen participants completed the trial. Total treatment response to tofacitinib was 37.5%. SALT50 was achieved in 12.5%. The mean improvement in SALT score was 15.57%. Mean maximum plasma concentration was 43.18 ng/ml occurring after 1 hour. Elimination half‐life is estimated to be up to 11 hours. An estimated half‐life of up to 11 hours may be achieved with sublingual tofacitinib, which is significantly longer than the oral form and may facilitate daily dosing. Larger clinical trials are required to further characterize its pharmacokinetics and efficacy.