Background/Purpose: Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis, vascular abnormalities, and immune system dysregulation. Current treatment options are limited, and there is a need for more effective therapies. Tofacitinib, a Janus kinase (JAK) inhibitor, has shown promise in treating various autoimmune diseases. This study aims to evaluate the efficacy and safety of tofacitinib in patients with early diffuse cutaneous systemic sclerosis in Bangladesh.

Methods: This open-label randomized controlled clinical trial was conducted in the Department of Rheumatology, BSMMU, Dhaka, from March 2022 to August 2023. A consecutive sampling method was applied. Forty-six patients were randomized into groups A and B following block randomization, each consisting of 23 patients. Group A was put on tofacitinib (5 mg) twice daily. Group B was put on cyclophosphamide 500 mg/m2 monthly. Primary efficacy was assessed by change in modified Rodnan skin score(mRSS) from baseline after 24 weeks. Secondary efficacy was measured by the change in Disease Activity Score-28 by C-reactive protein(CRP) and erythrocyte sedimentation rate(ESR). Bangla version of the Health Assessment Questionnaire-Disability Index (B-HAQ) response from baseline at 24 weeks was analyzed. Oral prednisolone (≤ 10 mg/day), calcium channel blockers, and phosphodiesterase 5 (PDE 5) inhibitors (sildenafil, tadalafil) were allowed to be used.. Follow-up will be done on the 4^th, 12^th, and 24^th weeks. History, physical examinations, and investigations assessed adverse effects. Changes in acute phase reactants and composite measures within the groups from baseline to 24 weeks were also analyzed.

Results: Per-protocol analysis showed that the mean reduction of mRSS was 7±2.89 and 10.17±2.92 in tofacitinib-treated patients and it was 5.26±2.42 and 8±4.08 in cyclophosphamide-treated patients after the 12^th and 24^th weeks (p<0.05). DAS28-ESR and DAS28-CRP reduction were significant between the groups from baseline to the 12^th and 24^th weeks (p<0.05). The functional status (measured by B-HAQ) reduction was 2.11±4.91 and 0.96±0.53 in tofacitinib and cyclophosphamide groups respectively ( p=.43). FVC change was 9.17±8.33 in tofacitinib group and 3.43±8.1 in cyclophosphamide group. Within the group’s other core set of outcomes, composite measures were significantly improved in the tofacitinib group. Two patients (8.7%) in the tofacitinib group and six patients (17.4%) in the cyclophosphamide group developed nausea. Two patients (8.7%) in both groups developed RTI (respiratory tract infection) and UTI (urinary tract infection). Taeniasis developed in three patients (13%) in the cyclophosphamide group. Two patients (8.7%) developed hemorrhagic cystitis in cyclophosphamide-treated patients.

Conclusion: Tofacitinib was effective with fewer side effects, in treating early diffuse cutaneous systemic sclerosis. Therefore, we may conclude that tofacitinib can open a new window in treating early diffuse cutaneous systemic sclerosis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-of-tofacitinib-in-the-treatment-of-early-diffuse-cutaneous-systemic-sclerosis-a-clinical-study-in-bangladesh/