Safety and Efficacy of Baricitinib on Skin Tightening in Diffuse Cutaneous Systemic Sclerosis: A Comparative Study With Methotrexate (BardSSc)

Systemic sclerosis (SSc) is a systemic autoimmune disease. It causes progressive skin tightening, pulmonary fibrosis, organ damage and many other physical dysfunctions. It is divided into two types, limited cutaneous systemic sclerosis (lcSSc) and diffuse cutaneous systemic sclerosis (dcSSCc). Skin involvement in systemic sclerosis is assessed by modified Rodnan skin score (mRSS). Methotrexate is a drug used in the treatment of skin tightening in SSc but has inconsistent response . Janus kinase (JAK) inhibitors are a class of drugs that may be used in skin involvement in dcSSc. Among them, baricitinib, a JAK 1/2 inhibitor, has shown some efficacy in dcSSc. The aim of this study is to assess the efficacy and safety of baricitinib on skin tightening in dcSSc patients. This open label randomized clinical trial will be conducted in department of rheumatology, BSMMU. Systemic sclerosis will be diagnosed by ACR/EULAR classification criteria 2013. Among them who have diffuse cutaneous involvement will be considered primary entry criteria for this study. Consecutive sampling method will be applied. Participants will be divided into two groups, group A and group B. Group A will be put on tab. baricitinib 4 mg daily and group B will be put on tab. methotrexate 25 mg weekly with folic acid 5 mg weekly. All participants will be assessed for mRSS, CDAI at baseline and laboratory tests like CBC, ESR, CRP, SGPT, serum creatinine, CXR P/A view etc. Follow up will be done at 4, 12, 24 weeks. Response to treatment will be assessed by modified Rodnan skin score. Primary endpoint of efficacy will be assessed by the end of 24th week. adverse effects will be assessed by history, physical examination and investigations. The data will be analyzed by SPSS version 25. results will be recorded using means and standard deviations. Result will be compared among groups with a 95% confidence interval and a p-value 0f<0.05. The degrees of statistical significance between groups will be analyzed by unpaired t test (for quantitative normally distributed data) and Mann Whitney U test for skewed distribution. Qualitative data in between groups will be analyzed by chi square test. Probabilities of association will be assessed by Spearman's rank correlation coefficient. P value of < 0.05 will be regarded as statistically significant.

Study Overview

• Status: Recruiting
• Conditions: Diffuse Cutaneous Systemic Sclerosis
• Intervention / Treatment: Drug: tab baricitinib 4 mg daily; Drug: tab methotrexate 25 mg weekly with folic acid 5 mg weekly

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Dr Md. Fahad Hossain, MBBS, MD; Phone Number: +8801811237435; Email: fhosen14@gmail.com
• Study Contact Backup: Name: Dr Md. Ariful Islam, MBBS, MD, FCPS; Phone Number: +8801730053723

Study Locations

• Bangladesh
  • Dhaka, Bangladesh
    • Recruiting
    • BSMMU
    • Contact: Fahad Hossain, MBBS, MD; Phone Number: +8801811237435; Email: fhosen14@gmail.com
    • Contact: Dr Ariful Islam, MBBS, FCPS, MD; Phone Number: +8801730053723; Email: ariful_islam7400@yahoo.com
    • Contact: Dr Md. Fahad Hossain, MBBS, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1. Diagnosis of diffuse cutaneous systemic sclerosis, as classified using the 2013 American College of Rheumatology

  2. Diffuse cutaneous systemic sclerosis as defined by 2001 LeRoy and Medsger 3. Disease duration ≤ 60 months (defined as time from the first non-Raynaud phenomenon manifestation) 4. mRSS score ≥ 10 at baseline

Exclusion Criteria:

Subjects with any of the following characteristics/conditions will not be included in the study:

1. Rheumatic disease other than systemic sclerosis. it is acceptable to include patients with fibromyalgia and scleroderma-associated myopathy
2. Limited cutaneous systemic sclerosis or sine scleroderma at the screening visit
3. Major surgery (including joint surgery) within 8 weeks prior to screening visit
4. Any infected ulcer prior to treatment
5. Subjects with any serious bacterial infection (e.g.,chronic pyelonephritis, osteomyelitis, or bronchiectasis) .
6. Oral corticosteroids >10 mg/day of prednisone or equivalent.
7. Mycophenolate mofetil > 2 grams/day prior to baseline
8. Pulmonary disease with FVC ≤ 50% of predicted, or DLCO (uncorrected for hemoglobin) ≤ 40% of predicted
9. Current clinical, radiographic, or laboratory evidence of active TB.
10. Positive for hepatitis B surface antigen at or within 30 days of screening.
11. Positive for hepatitis C antigen at or within 30 days of screening.
12. Current or recent history of uncontrolled clinically significant renal, hepatic, hematologic, gastrointestinal, metabolic, endocrine, pulmonary, cardiac or neurologic disease.
13. Pregnant or breastfeeding female subjects and female subjects of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in the protocol for the duration of the study and for at least 28 days after discontinuation of study drug.
14. History of any malignancy in the last 5 years
15. History of SSc Renal Crisis within the 6 months prior to baseline.
16. Patients with a history of anaphylaxis to Baricitinib or methotrexate

17. Any of the following lab results at screening:

    • Hemoglobin <8 g/dl
    • White Blood Cell count <3.0 x 109/L;
    • Absolute Neutrophil count <1.2 x 109/L;
    • Platelet count <100 x 109/L;
    • Absolute Lymphocyte count <0.75 x 109/L.
    • ALT > 3 × the upper limit of normal (ULN) of normal at screening
    • Estimated glomerular filtration rate [GFR] <60mL/min/1.73 m2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; Group A participants will get tab. baricitinib 4 mg daily	Drug: tab baricitinib 4 mg daily; Group A participants will be given tab. Baricitinib 4 mg daily
Active Comparator: Group B; Group B participants will be given tab. Methotrexate 25 mg weekly with folic acid 5 mg weekly	Drug: tab methotrexate 25 mg weekly with folic acid 5 mg weekly; group A participants will be given tab. baricitinib 4 mg daily and group B participants will be given tab. methotrexate 25 mg weekly with folic acid 5 mg weekly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in mRSS score	mRSS score is recorded at baseline and change in mRSS score is measured in subsequent follow ups at 4, 12 and 24 weeks	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in CDAI score	Baseline clinical disease activity index (CDAI) is recorded and is measured in subsequent follow ups at 4, 12 and 24 weeks	24 weeks
See the side effects of drugs	side effect of group A and group B is recorded at 4, 12 and 24 weeks	24 weeks

Collaborators and Investigators

• Sponsor: Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
• Investigators: Principal Investigator: Dr MD. Fahad Hossain, MBBS, MD, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: April 12, 2025
• First Submitted That Met QC Criteria: April 12, 2025
• First Posted (Actual): April 20, 2025

Study Record Updates

• Last Update Posted (Actual): April 20, 2025
• Last Update Submitted That Met QC Criteria: April 12, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Baricitinib in diffuse cutaneous systemic sclerosis
• Additional Relevant MeSH Terms: Pathologic Processes; Connective Tissue Diseases; Skin Diseases; Sclerosis; Scleroderma, Systemic; Scleroderma, Diffuse; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Reproductive Control Agents; Antimetabolites, Antineoplastic; Antimetabolites; Dermatologic Agents; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors; Micronutrients; Vitamin B Complex; Vitamins; Hematinics; Methotrexate; Folic Acid
• Other Study ID Numbers: 5011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: participants may not allow sharing all informations with others other than investigator

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