A Pilot Randomized Controlled Trial Comparing the Efficacy and Safety of Oral Tofacitinib Versus Methotrexate In...

Treatments for moderate-to-severe alopecia areata (AA) have limited efficacy. Methotrexate, a conventional immunosuppressant, has been used for AA, while Janus kinase/signal transducer and activator of transcription (JAK-STAT) inhibitors like tofacitinib have shown promising results.

To compare the efficacy of tofacitinib and methotrexate in moderate-to-severe AA.

Thirty-six patients aged 18-60 years with a severity of alopecia tool (SALT) score >40 were randomized to receive either tofacitinib (5-10 mg twice daily) or methotrexate (0.3-0.5 mg/kg weekly) for 6 months, followed by 3-month follow-up. Primary outcomes measured the proportion achieving a SALT score ≤20 at 6 months. Secondary outcomes included patient-reported outcome (PRO) on scalp hair assessment, dermatology life quality index (DLQI), patient health questionnaire (PHQ) scores, relapse rates, and alkaline phosphatase (ALP) activity in scalp biopsies.

At 6 months, 50% of tofacitinib patients achieved a SALT score ≤20 vs. 33.3% with methotrexate ( P = 0.31). A ≥ 90% SALT improvement occurred in 33.3% of tofacitinib and 11.1% of methotrexate patients ( P = 0.10). The tofacitinib group had greater scalp hair PRO score reductions. Both groups showed significant DLQI and PHQ improvements, with no intergroup differences. Adverse events were reported in 38.8% of tofacitinib and 33.3% of methotrexate patients ( P = 1). ALP activity was inconclusive.

Small sample size, open-label design, lack of stratification, and baseline imbalances that may affect achievable improvement and comparative interpretation.

In this pilot trial, both tofacitinib and methotrexate improved SALT score, PRO score, and psychological outcomes, but the tofacitinib group showed greater efficacy. Larger studies are warranted to confirm findings and investigate ALP activity.