BH06 (P075) A randomized controlled trial comparing the efficacy and safety of oral tofacitinib vs. methotrexate in moderate-to-severe alopecia areata

Abstract Treatment options for moderate-to-severe alopecia areata (AA) have limited efficacy. Methotrexate, a conventional immunosuppressant, has been used for AA, while Janus kinase inhibitors like tofacitinib have shown promising results. Our aim was to compare the efficacy and safety of oral tofacitinib and methotrexate in treating moderate-to-severe AA. This study recruited 36 patients with moderate-to-severe AA, aged 18–60 years, with a Severity of Alopecia Tool (SALT) score > 40 (Olsen EA, Hordinsky MK, Price VH et al. Alopecia areata investigational assessment guidelines – part II. National Alopecia Areata Foundation. J Am Acad Dermatol 2004; 51: 440–7). Participants were randomized to receive either tofacitinib (5–10 mg twice daily; Group A) or methotrexate (0.3–0.5 mg kg−1 weekly; Group B) for 6 months, followed by a 3-month follow-up. The primary outcome was the proportion of patients achieving a SALT score ≤ 20 after 6 months of treatment. Secondary outcomes included patient-reported outcomes (PROs) on scalp hair assessment, changes in the Dermatology Life Quality Index (DLQI), Patient Health Questionnaire (PHQ) scores, and relapse rates (Wyrwich KW, Kitchen H, Knight S et al. Development of the Scalp Hair Assessment PROTM measure for alopecia areata. Br J Dermatol 2020; 183: 1065–72). Additionally, alkaline phosphatase activity in scalp biopsies was assessed. At 6 months, 50% of patients in Group A achieved a SALT score ≤ 20 compared with 33% in Group B (P = 0.31). More than 90% improvement in SALT score was observed in 33% in of patients in Group A and 11% in Group B (P = 0.11). Patients in Group A demonstrated greater reduction scalp hair assessment PRO score. Relapse rates (while the drug was tapered) were 50% in Group A and 33% in Group B (P = 0.31). DLQI and PHQ scores in both groups showed a statistically significant reduction, with no significant intergroup differences. Adverse events occurred in 39% of patients in Group A and 33% in Group B (P > 0.99), with no serious adverse effects or hospitalizations. In Group A, common adverse events included dyslipidaemia (17%), scalp folliculitis (11%), leucopenia (6%), renal stones (6%) and severe headache (6%). In Group B, transaminitis (17%), scalp folliculitis (6%), varicella infection (6%) and fever with cytopenias (6%) were noted. Alkaline phosphatase activity was inconclusive and did not correlate with disease severity or treatment response. Both tofacitinib and methotrexate effectively reduced SALT scores, improved scalp hair assessment PRO scores, and alleviated psychological distress without significant adverse effects. However, tofacitinib demonstrated much greater efficacy. Larger studies are warranted to confirm these findings and explore the underlying mechanisms behind the differences, particularly in alkaline phosphatase activity.