Intravenous cyclophosphamide vs rituximab for the treatment of early diffuse scleroderma lung disease: open label, randomized, controlled trial

• Published in: Rheumatology (Oxford, England) Vol. 57; no. 12; pp. 2106 - 2113
• Main Authors: Sircar, Geetabali, Goswami, Rudra Prosad, Sircar, Dipankar, Ghosh, Alakendu, Ghosh, Parasar
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.12.2018
• Subjects: Adult; Antirheumatic Agents - therapeutic use; Cyclophosphamide - therapeutic use; Disease Progression; Female; Humans; Lung - pathology; Lung Diseases, Interstitial - drug therapy; Lung Diseases, Interstitial - etiology; Male; Rituximab - therapeutic use; Scleroderma, Diffuse - complications; Scleroderma, Diffuse - drug therapy; Scleroderma, Diffuse - pathology; Severity of Illness Index; Skin - pathology; Treatment Outcome; Vital Capacity - drug effects; Walk Test; cyclophosphamide; interstitial lung disease; modified Rodnan skin score; diffuse systemic sclerosis; rituximab; forced vital capacity
• DOI: 10.1093/rheumatology/key213
• ISSN: 1462-0324; 1462-0332

Abstract Objectives SSc is characterized by fibrotic changes in the skin and lung, and the mainstay of treatment has been CYC. B cell involvement suggests that rituximab (RTX) may also be of therapeutic benefit. The aim of the study was to compare the efficacy and safety of RTX compared with CYC in retarding the progression of interstitial lung disease and skin manifestations of primary SSc. Methods We randomly assigned 60 patients of dcSSc, age 18-60 years with skin and lung involvement, to monthly pulses of CYC 500 mg/m2 or RTX 1000 mg × 2 doses at 0, 15 days. Primary outcomes were forced vital capacity (FVC) percent predicted at 6 months. Secondary outcomes were: absolute change in litres (FVC-l) at 6 months; modified Rodnan skin scores at 6 months, 6-min walk test, Medsgers score and new onset or worsening of existing pulmonary hypertension by echocardiographic criteria. Results The FVC [%mean (s.d.)] in the RTX group improved from 61.30 (11.28) to 67.52 (13.59), while in the CYC group it declined from 59.25 (12.96) to 58.06 (11.23) at 6 months (P = 0.003). The change of FVC was 1.51 (0.45) l to 1.65 (0.47) l in the RTX group, compared with 1.42 (0.49) to 1.42 (0.46) l in the CYC group. The mRSS changed from 21.77 (9.86) to 12.10 (10.14) in the RTX group and 23.83 (9.28) to 18.33 (7.69) in the CYC group after 6 months. Serious adverse events were more common in the CYC group. Conclusion RTX is a safe and effective alternative to CYC in the primary therapy of skin and lung manifestations of scleroderma. Trial registration Clinical Trials Registry - India, www.ctri.nic.in, CTRI/2017/07/009152.