A Comparative Study of Oral Tofacitinib and Oral Methotrexate in the Treatment of Patients With Moderate to Severe Chronic Plaque Psoriasis

TL;DR

This study compares tofacitinib and methotrexate for treating severe psoriasis, finding that tofacitinib acts faster and achieves better skin clearance.

Contribution

The study provides comparative efficacy and safety data of tofacitinib and methotrexate in an Indian population with chronic plaque psoriasis.

Findings

Tofacitinib showed faster onset of action with higher PASI 75 response by week 12 compared to methotrexate.

Tofacitinib achieved significantly higher PASI 90 response at week 16 than methotrexate.

Both drugs had similar overall efficacy but tofacitinib provided deeper clinical clearance.

Abstract

Background

Chronic plaque psoriasis is a common immune-mediated dermatosis that often requires long-term systemic therapy in patients with moderate to severe disease. Methotrexate has been a cornerstone of systemic treatment for decades; however, concerns regarding delayed onset of action, cumulative toxicity, and the need for close laboratory monitoring have driven interest in newer targeted oral therapies. Tofacitinib, an oral Janus kinase (JAK) inhibitor, modulates multiple cytokine signaling pathways implicated in psoriasis pathogenesis, though comparative data from the Indian population remain limited.

Objectives

The present study aimed to compare the efficacy, time to response, relapse rates, and safety profile of oral tofacitinib versus oral methotrexate in patients with moderate to severe chronic plaque psoriasis.

Methods

This prospective, randomized, open-label comparative study was conducted over 18 months (August 2023 to January 2025) at Great Eastern Medical School & Hospital, a tertiary care teaching hospital in South India. Adult patients with biopsy-proven chronic plaque psoriasis of at least three months’ duration, a Psoriasis Area and Severity Index (PASI) score greater than 10, and body surface area involvement exceeding 10% were enrolled. Forty-two eligible patients were randomized into two groups: Group A (n = 21) received oral tofacitinib 5 mg twice daily, while Group B (n = 21) received oral methotrexate 10 mg once weekly with folic acid supplementation. Clinical assessment using PASI was performed at baseline and at two, four, eight, 12, and 16 weeks. Treatment efficacy, PASI 75 and PASI 90 responses, time to PASI 75, relapse, and adverse events were analyzed.

Results

Both treatment groups demonstrated a progressive and statistically significant reduction in mean PASI scores over the 16-week treatment period, with no statistically significant difference in mean PASI reduction between the two groups at individual follow-up visits. Tofacitinib showed a faster onset of action, with a higher proportion of patients achieving PASI 75 by week 12 (57.1%), whereas methotrexate demonstrated a higher cumulative PASI 75 response by week 16 (71.4%). Achievement of PASI 90 at week 16 was significantly higher in the tofacitinib group compared to the methotrexate group (57.1% vs. 19.0%; p < 0.05). Relapse was observed more frequently in the methotrexate group, although this difference did not reach statistical significance. Mild elevation of liver enzymes was the most commonly observed adverse effect in both groups, and no serious adverse events were recorded.

Conclusion

Oral tofacitinib and methotrexate are both effective systemic therapies for moderate to severe chronic plaque psoriasis. Tofacitinib offers the advantage of faster and deeper clinical clearance, while methotrexate demonstrates comparable efficacy over a longer treatment duration. Tofacitinib may be considered a useful oral alternative in patients requiring rapid disease control.

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