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

Study Overview

• Status: Not yet recruiting
• Conditions: Alopecia Areata; Alopecia Universalis; Alopecia Totalis (AT)
• Intervention / Treatment: Drug: Tofacitinib; Drug: Methotrexate

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 78
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Hira Rehman, FCPS; Phone Number: 03359849292; Email: khira420.hr@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tofacitinib 10 mg Twice Daily; Participants will receive oral tofacitinib 10 mg twice daily for 12 weeks. Clinical response will be assessed using the SALT score at baseline and at week 12. Efficacy is defined as >50% improvement in SALT score from baseline.	Drug: Tofacitinib; Oral tofacitinib 10 mg twice daily for 12 weeks.
Active Comparator: Methotrexate 0.2-0.4 mg/kg Weekly; Participants will receive oral methotrexate 0.2-0.4 mg/kg once weekly for 12 weeks with routine follow-up and laboratory monitoring for adverse effects as per institutional protocol. Clinical response will be assessed using the SALT score at baseline and at week 12. Efficacy is defined as >50% improvement in SALT score from baseline.	Drug: Methotrexate; Oral methotrexate 0.2-0.4 mg/kg once weekly for 12 weeks, with routine monitoring for adverse effects as per institutional protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Severity of Alopecia Tool (SALT) Score	SALT score ranges from 0 to 100, with higher scores indicating greater scalp hair loss. The primary outcome is the change in SALT score from baseline to week 12, compared between the tofacitinib and methotrexate groups.	Week 12

Collaborators and Investigators

• Sponsor: Hayat Abad Medical Complex, Peshawar

Publications and helpful links

General Publications

• Abe DT, Tashima LM, Basilio FMA, Mulinari-Brenner F. Clinical experience with oral tofacitinib in a patient with alopecia areata universalis and rheumatoid arthritis. Int J Trichology. 2020;12(4):188-90.
• Asma JK, Huma AS, Urooj M. A study on the role of tofacitinib among patients treated with alopecia areata. Pak J Med Health Sc. 2022;16(12):801-3.
• Iorizzo M, Tosti A. Emerging drugs for alopecia areata: JAK inhibitors. Expert Opin Emerg Drugs. 2018;23(1):77-81.
• Cervantes J, Jimenez JJ, DelCanto GM, Tosti A. Treatment of alopecia areata with simvastatin/ezetimibe. J Investig Dermatol Symp Proc. 2018;19(1):S25-S31.
• Strazzulla LC, Avila L, Lo Sicco K, Shapiro J. an overview of the biology of platelet-rich plasma and microneedling as potential treatments for alopecia areata. J Investig Dermatol Symp Proc. 2018;19(1):S21-S24.
• Lee S, Kim BJ, Lee YB, Lee WS. Hair Regrowth outcomes of contact immunotherapy for patients with alopecia areata: a systematic review and meta-analysis. JAMA Dermatol. 2018;154(10):1145-51.
• Ro BI. Alopecia areata in Korea (1982-1994). J Dermatol. 1995;22(11):858-64.
• Melo DF, Dutra TBS, Baggieri VMAC, Tortelly VD. Intralesional betamethasone as a therapeutic option for alopecia areata. an Bras Dermatol. 2018;93(2):311-12
• Chu TW, AlJasser M, Alharbi A, Abahussein O, McElwee K, Shapiro J, et al. Benefit of different concentrations of intralesional triamcinolone acetonide in alopecia areata: an intrasubject pilot study. J Am Acad Dermatol. 2015;73(2):338-40.
• Messenger AG, McKillop J, Farrant P, McDonagh AJ, Sladden M. British Association of Dermatologists' guidelines for the management of alopecia areata 2012. Br J Dermatol. 2012;166(5):916-26.
• Rajabi F, Drake LA, Senna MM, Rezaei N. Alopecia areata: a review of disease pathogenesis. Br J Dermatol. 2018;179(5):1033-48.
• Mirzoyev SA, Schrum AG, Davis MDP, Torgerson RR. Lifetime incidence risk of alopecia areata estimated at 2.1% by Rochester Epidemiology Project, 1990-2009. J Invest Dermatol. 2014;134(4):1141-2.
• Safavi KH, Muller SA, Suman VJ, Moshell AN, Melton LJ. Incidence of alopecia areata in Olmsted County, Minnesota, 1975 through 1989. Mayo Clin Proc. 1995;70(7):628-33
• Pratt CH, King LE, Messenger AG, Christiano AM, Sundberg JP. Alopecia areata. Nat Rev Dis Primers. 2017;3:17011.
• Gilhar A, Etzioni A, Paus R. Alopecia areata. N Engl J Med. 2012;366(16):1515-5.

Study record dates

Study Major Dates

• Study Start (Estimated): February 15, 2026
• Primary Completion (Estimated): August 15, 2026
• Study Completion (Estimated): August 15, 2026

Study Registration Dates

• First Submitted: February 5, 2026
• First Submitted That Met QC Criteria: February 5, 2026
• First Posted (Actual): February 12, 2026

Study Record Updates

• Last Update Posted (Actual): February 12, 2026
• Last Update Submitted That Met QC Criteria: February 5, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Methotrexate; Tofacitinib; Janus Kinase Inhibitor; Autoimmune Hair Loss; Severe Alopecia Areata
• Additional Relevant MeSH Terms: Skin Diseases; Alopecia; Hypotrichosis; Hair Diseases; Skin and Connective Tissue Diseases; Alopecia Areata; Alopecia universalis; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pterins; Pteridines; Aminopterin; Methotrexate; tofacitinib
• Other Study ID Numbers: HMC-DERM-TOFA-MTX-AA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be shared because this is an investigator-initiated, single-center study and data sharing is not covered in the participant consent/IRB approvals. De-identified aggregate results will be reported in publications and presentations. De-identified data may be considered for sharing in the future upon reasonable request after publication, subject to additional ethical approvals and a data use agreement.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No