Efficacy of Tofacitinib on Skin Thickening in Diffuse Cutaneous Systemic Sclerosis: A Comparative Study With Methotrexate

This study aims to evaluate the efficacy of Tofacitinib compared to Methotrexate (MTX) in reducing skin thickening in patients with diffuse cutaneous systemic sclerosis (dcSSc). Systemic sclerosis is a chronic autoimmune disease characterized by skin fibrosis and internal organ involvement. Despite existing treatments, many patients continue to experience progressive skin and joint symptoms.

Tofacitinib, a Janus kinase (JAK) inhibitor, has shown potential benefit in reducing inflammation and fibrosis in autoimmune diseases. This randomized controlled study will compare the change in Modified Rodnan Skin Score (mRSS), Clinical Disease Activity Index (CDAI), and 12-Item Short Form Survey (SF-12) between the Tofacitinib and Methotrexate groups over the study period.

The study will also monitor adverse events and laboratory parameters to assess drug safety and tolerability.

Study Overview

• Status: Completed
• Conditions: Scleroderma, Systemic
• Intervention / Treatment: Drug: Tofacitinib; Drug: Methotrexate

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 4

Contacts and Locations

Study Locations

• Bangladesh
  • Dhaka, Bangladesh, 1000
    • Department of Rheumatology, Bangabandhu Sheikh Mujib Medical University (BSMMU)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1. Diagnosed with systemic sclerosis (SSc) according to the 2013 ACR/EULAR classification criteria 2. Classified as having diffuse cutaneous systemic sclerosis (dcSSc), as defined by LeRoy and Medsger 3. Disease duration of ≤ 36 months, calculated from the onset of the first non-Raynaud's phenomenon manifestation.

  4. Modified Rodnan Skin Score (mRSS) between 10 and 45 at the time of screening.

  5. Concurrent use of calcium channel blockers and phosphodiesterase-5 inhibitors for the treatment of Raynaud's phenomenon or digital ulcers was permitted.

  6. Subjects were aged 18 years and older

Exclusion Criteria:

• 1. Presence of a rheumatic disease other than systemic sclerosis, except for fibromyalgia or scleroderma-associated myopathy.

  2. Evidence of any active infection, including active tuberculosis 3. Abnormal laboratory values at screening, including:

  • Hemoglobin <9 g/dL
  • White blood cell count <3.0 × 10⁹/L
  • Absolute neutrophil count <1.2 × 10⁹/L
  • Platelet count <100 × 10⁹/L
  • Absolute lymphocyte count <0.75 × 10⁹/L
  • ALT or AST >3× the upper limit of normal (ULN)

  • Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m²

    4. Pulmonary function showing forced vital capacity (FVC) ≤ 50% predicted, or DLCO (uncorrected for hemoglobin) ≤ 40% predicted.

    5. History of major surgery (including joint surgery) within 8 weeks prior to the screening visit.

    6. Use of oral corticosteroids 7. Diagnosis of latent TB at or within 30 days of screening. 8. Positive hepatitis B surface antigen or anti HCV test at or within 30 days of screening.

    9. Pregnant or breastfeeding women, females of childbearing potential who were unwilling or unable to use highly effective contraception during the study 10. History or evidence of malignancy 11. Receipt of a live or attenuated vaccine within 6 weeks prior to baseline

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
Active Comparator: Methotrexate group	Drug: Methotrexate; 25mg orally once weekly for 24 weeks
Experimental: Tofacitinib group	Drug: Tofacitinib; Tofacitinib: 5mg orally twice daily for 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Modified Rodnan Skin Score (mRSS) from baseline to week 24 Scale range: 0 (no skin thickening) to 51 (most severe skin thickening) Higher score indicate worse skin thickening (worse outcome)	Baseline and Week 24

Collaborators and Investigators

• Sponsor: Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
• Investigators: Study Chair: Md. Abu Shahin, FCPS, MD, Department of Rheumatology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2024
• Primary Completion (Actual): August 30, 2025
• Study Completion (Actual): August 30, 2025

Study Registration Dates

• First Submitted: March 9, 2026
• First Submitted That Met QC Criteria: March 11, 2026
• First Posted (Actual): March 16, 2026

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 11, 2026
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Methotrexate; Tofacitinib; Autoimmune disease; mRSS; Skin thickening
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Immune System Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Scleroderma, Systemic; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pterins; Pteridines; Aminopterin; Methotrexate; tofacitinib
• Other Study ID Numbers: 5230

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No