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

Inclusion criteria

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

• 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:

• Rheumatic disease other than systemic sclerosis. it is acceptable to include patients with fibromyalgia and scleroderma-associated myopathy
• Limited cutaneous systemic sclerosis or sine scleroderma at the screening visit
• Major surgery (including joint surgery) within 8 weeks prior to screening visit
• Any infected ulcer prior to treatment
• Subjects with any serious bacterial infection (e.g.,chronic pyelonephritis, osteomyelitis, or bronchiectasis) .
• Oral corticosteroids >10 mg/day of prednisone or equivalent.
• Mycophenolate mofetil > 2 grams/day prior to baseline
• Pulmonary disease with FVC ≤ 50% of predicted, or DLCO (uncorrected for hemoglobin) ≤ 40% of predicted
• Current clinical, radiographic, or laboratory evidence of active TB.
• Positive for hepatitis B surface antigen at or within 30 days of screening.
• Positive for hepatitis C antigen at or within 30 days of screening.
• Current or recent history of uncontrolled clinically significant renal, hepatic, hematologic, gastrointestinal, metabolic, endocrine, pulmonary, cardiac or neurologic disease.
• 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.
• History of any malignancy in the last 5 years
• History of SSc Renal Crisis within the 6 months prior to baseline.
• Patients with a history of anaphylaxis to Baricitinib or methotrexate
• 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