medwireNews: Results of an open-label randomized trial suggest that rituximab may be an appropriate alternative to cyclophosphamide for treating lung and skin disease associated with systemic sclerosis (SSc).
As reported in Rheumatology, the 30 patients with diffuse cutaneous SSc with lung and skin involvement who were randomly assigned to receive rituximab experienced a significant improvement in average percent-predicted forced vital capacity (FVC), from 61.30% at baseline to 67.52% at the 6-month follow-up.
Conversely, their 30 counterparts who received cyclophosphamide experienced a small decrease in average percent-predicted FVC from 59.25% to 58.06% over the same period, giving a significant difference of 9.46% between the groups favoring rituximab.
Rituximab was given as two intravenous pulses at a dose of 1000 mg following premedication with paracetamol 500 mg and prednisolone 10 mg, while the cyclophosphamide group received intravenous pulses at a dose of 500 mg/m2 every 4 weeks for a total of 24 weeks. All patients received prednisolone 10 mg/day, calcium, and vitamin D throughout the study.
The lower limit of the 95% confidence interval of the difference in average percent-predicted FVC between the groups was greater than the noninferiority margin, but Geetabali Sircar (Institute of Postgraduate Medical Education and Research, Kolkata, India) and co-investigators caution that their study “was not set up to detect superiority.”
Patients in the rituximab also experienced a greater improvement in the modified Rodnan skin score than those in the cyclophosphamide group, with mean decreases of 9.67 versus 5.50 points
In all, 30% of patients in the rituximab group and 70% of those given cyclophosphamide experienced adverse events. One patient treated with rituximab died after developing severe pulmonary arterial hypertension 5 months after completing the trial, while one patient in the cyclophosphamide group developed scleroderma renal crisis and died 3 months after the last dose of the study drug.
Among participants in the cyclophosphamide group, two experienced premature ovarian failure, while gangrene and malignancy were each reported in one patient. None of these adverse events occurred in patients given rituximab, but infusion-related reactions were more common in the rituximab than cyclophosphamide group (three vs zero patients).
Rituximab “was associated with at least similar efficacy and had significantly fewer major adverse events than [cyclophosphamide] over the study period of 6 months,” summarize Sircar and team. They concede, however, that their study was limited by its short duration of follow-up and single center, open-label design.
And the researchers conclude: “A larger clinical trial of [rituximab] with long-term follow-up should be planned in patients with scleroderma for better assessment of durability and generalizability of its clinical efficacy.”
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