Background Systemic Sclerosis (SSc) is a rare systemic disease characterized by immune abnormalities, widespread vascular injury and progressive fibrosis of skin and internal organs. Currently, only few therapeutic options have shown a proved disease-modifying effect for skin thickening and SSc-associated interstitial lung disease.
Objectives To assess efficacy and safety of a combination therapy, with rituximab (RTX) and mycophenolate ofetil (MMF), in rapidly progressive or resistant to conventional therapy SSc patients with pulmonary and cutaneous involvement.
Methods Patients received RTX infusion (1000 mg at day 0 and after two weeks) at baseline and after 6 months, associated with MMF 2000 mg/day from day + 15. They received anti-infective prophylaxis whit valacyclovir 1000 mg and cotrimoxazole 160/800 mg alternate days. Patients with previous malignancy or HBV, HCV or TB infection were excluded. Patients underwent clinical and laboratory evaluation every 3 months. Skin involvement was assessed by using the modified Rodnan Skin Score (mRSS). The chest high-resolution computed tomography (HRCT) and the pulmonary function tests and single-breath diffusing capacity were performed at baseline and after 6 and 12 months. Lung fibrosis at the HRCT scans was analyzed with a semi-quantitative scoring method (Fraticelli P et al. Arthritis Res Ther. 2014 Jul 8;16(4):R144). Forced vital capacity (FVC), total lung capacity (TLC) and diffusing capacity of the lung for carbon monoxide (DLCO) were considered for pulmonary function assessment. Data were analyzed by Wilcoxon matched paired signed rank test.
Results Eighteen SSc patients were enrolled (M/F: 8/10, median duration of disease 52 y, median age 2y, diffuse SSc 9, limited SSc 9). Two patients withdrew from the clinical study, one was lost to follow-up and the other one had a minor infusion reaction which led to RTX discontinuation. The preliminary analysis includes 12 of 18 patients who completed the 6 month follow-up. The mRSS showed a trend to improvement (p=0.1347), which, however, was not statistically significant. The improvement in patients with the diffuse cutaneous SSc was more remarkable. There was a significantly increase of FVC (p=0.0494) and TLC (p=0.0412); DLCO (p=0.7891) improved but not significantly. The HRCT pattern improved in two patients reduction of the number of lung segments with ground-glass appearance, while patients with prevalent reticular pattern or advanced honeycombing remained stable. No serious adverse events were observed during the follow-up. In one patient the MMF dose was reduced for mild neutropenia and one patient required cotrimoxazole discontinuation for mild macrocytic anemia.
Conclusions Despite preliminary and limited to a small number of patients, our results suggest that combination therapy with RTX and MMF is well tolerated, safe, and potentially effective for cutaneous and pulmonary involvement in SSc patients.
Disclosure of Interest None declared