Rituximab is a safe and effective alternative to cyclophosphamide when used to manage the progression of scleroderma and subsequent development of interstitial lung disease and hypertensive complications, according to a study published in Rheumatology.
This prospective, randomized, open-label study sought to compare rituximab and intravenous cyclophosphamide as primary therapies for slowing the progression of systemic scleroderma, specifically by monitoring lung function and skin manifestations.
The study included 60 patients between the ages of 18 and 60 who were diagnosed with diffuse systemic scleroderma involving the skin and lung. Participants were randomly assigned to receive monthly pulses of cyclophosphamide 500 mg/m2 (n=30) or 2 doses of rituximab 1000 mg (n=30) at days 0 and 15 for 6 months. The medical history of each participant was taken at baseline; physical examination, laboratory tests, and imaging tests were performed at baseline and 24 weeks.
The primary study outcome was the predicted the percent of forced vital capacity (FVC) at 6 months; secondary outcomes calculated absolute change in liters of FVC, modified Rodnan skin scores, 6-minute walk distance, and Medsgers score. Echocardiogram was used to identify new onset or worsening of pulmonary hypertension.
No significant differences were reported in baseline values of the 2 groups. The predicted percent of FVC of the rituximab group improved significantly from 61.30 to 67.52 at the end of study, while the FVC in the cyclophosphamide group decreased slightly from 59.25 to 58.06. Secondary outcomes all favored rituximab. The change in FVC after 6 months was 1.51 to 1.65 liters in the rituximab group, while no change was reported in the cyclophosphamide group.
The modified Rodnan skin scores decreased from 21.77 to 12.10 in the rituximab group, and from 23.83 to 18.33 in the cyclophosphamide group. Both groups saw improvements in Medsger severity scores, but only participants in the rituximab group improved their 6-minute walk distance. Serious adverse events were more frequent in the cyclophosphamide group.
Limitations included a short follow-up period and the single-center, open-label design of the study suggesting potential bias from nonblinding. Financial constraints also limited the ability of the researchers to measure diffusion capacity of carbon monoxide and right heart catheterizations. Finally, smokers were excluded from the study, which may have benefited the outcome of the FVC measures.
Although both rituximab and cyclophosphamide treatments improved percent-predicted FVC outcomes, only participants taking rituximab saw improvement in all secondary measures (whereas cyclophosphamide only improved modified Rodnan skin scores and Medsger scores). The investigators suggested that rituximab is a safe and effective alternative to cyclophosphamide in treating systemic scleroderma with interstitial lung disease.
Sircar G, Goswami RP, Sircar D, Ghosh A, Ghosh P. Intravenous cyclophosphamide vs rituximab for the treatment of early diffuse scleroderma lung disease: open label, randomized, controlled trial [published online July 26, 2018]. Rheumatology. doi:10.1093/rheumatology/key213