Tofacitinib vs Methotrexate for Severe Alopecia Areata (TOFA-MTX-AA)

Comparative Clinical Efficacy of Tofacitinib Versus Methotrexate in Severe Alopecia Areata, Alopecia Totalis, and Alopecia Universalis: A Randomized Controlled Trial

This study will compare two oral medicines-tofacitinib and methotrexate-for treating severe alopecia areata, including alopecia totalis (loss of all scalp hair) and alopecia universalis (loss of scalp and body hair). Alopecia areata is an autoimmune condition that can cause significant hair loss and emotional distress.

Adults aged 18 to 60 years with severe disease will be enrolled at the Department of Dermatology, MTI-Hayatabad Medical Complex, Peshawar, after ethical approval and written informed consent. Participants will be randomly assigned to receive either tofacitinib 10 mg twice daily or methotrexate 0.2-0.4 mg/kg once weekly for 12 weeks.

The main outcome will be improvement in hair loss measured by the Severity of Alopecia Tool (SALT) score. Treatment will be considered effective if there is more than 50% improvement in SALT score from baseline at the end of 12 weeks. Safety will be monitored during follow-up visits. The findings may help guide treatment decisions for severe alopecia areata in our local population.

This is a single-center, parallel-group, randomized controlled trial to compare the clinical efficacy of oral tofacitinib versus methotrexate in adults with severe alopecia areata, including alopecia totalis and alopecia universalis, conducted at the Department of Dermatology, MTI-Hayatabad Medical Complex, Peshawar.

After approvals from the Institutional Ethical Committee and CPSP-REU and after obtaining written informed consent, eligible participants aged 18-60 years with severe alopecia areata/totalis/universalis diagnosed by a consultant dermatologist will be enrolled using consecutive non-probability sampling. Patients already receiving systemic therapy for hair regrowth, pregnant women, and patients with renal, hepatic, or pulmonary disease (based on history and clinical assessment) will be excluded.

Baseline demographic and clinical data will be recorded, and baseline disease severity will be assessed using the Severity of Alopecia Tool (SALT) score. Participants will be randomized using blocked randomization into two treatment arms:

Arm A: Oral tofacitinib 10 mg twice daily for 12 weeks.

Arm B: Oral methotrexate 0.2-0.4 mg/kg once weekly for 12 weeks, with scheduled follow-up and laboratory monitoring for potential adverse effects as per institutional protocol.

Participants will be reviewed every 4 weeks during treatment. At the end of 12 weeks, the SALT score will be reassessed. The primary endpoint is clinical efficacy defined a priori as >50% improvement in SALT score from baseline at week 12. Safety and tolerability will be assessed through clinical review and routine monitoring during follow-up visits.

Data will be analyzed using SPSS (version 23.0). Quantitative variables (e.g., age, duration of disease, baseline and post-treatment SALT scores) will be summarized as mean ± standard deviation, and categorical variables (e.g., gender, residence, efficacy) will be presented as frequency and percentage. Efficacy between groups will be compared using the chi-square test, and stratification will be performed for age group, gender, residence, and disease duration; post-stratification chi-square testing will be applied. A p-value <0.05 will be considered statistically significant.

Inclusion Criteria:

Adults aged 18-60 years.

Clinical diagnosis of severe alopecia areata, alopecia totalis, or alopecia universalis (as per protocol/operational definition), confirmed by a consultant dermatologist.

Either sex.

Able and willing to provide written informed consent.

Exclusion Criteria:

Currently receiving or recently used any systemic treatment intended for hair regrowth for alopecia areata (e.g., systemic corticosteroids, immunosuppressants, JAK inhibitors).

Pregnant women.

History or clinical evidence of renal, hepatic, or pulmonary disease.

Any condition that, in the investigator's judgment, makes participation unsafe or interferes with adherence to the study protocol.