Background Systemic Sclerosis (SSc) is a chronic systemic disease characterized by immune abnormalities, microangiopathy and progressive fibrosis of skin and internal organs. Only few therapeutic options have shown a proved disease-modifying effect for skin thickening and SSc-associated interstitial lung disease. Rituximab (RTX) and Mycophenolate Mofetil (MMF) have separately proven some evidence of efficacy and safety in clinical trials or case series
Objectives Assess efficacy and safety of a combination therapy, with RTX and MMF in a cohort of SSc patients with pulmonary and cutaneous involvement rapidly progressive or resistant to conventional therapy.
Methods Eligible patients were treated with RTX in two different regimens (1000 mg fortnightly x 2 or 375 mg/m2/week for 4 consecutive weeks) at baseline and after 6 months, associated with MMF 2000 mg/day. They received anti-infective prophylaxis with Valacyclovir 1000 mg and Cotrimoxazole 160/800 mg alternate days. Patients with previous malignancy or HBV, HCV or TB infection or connective overlap were excluded. Patients underwent clinical and laboratory evaluation every 3 months. Skin involvement was assessed by using the modified Rodnan Skin Score (mRSS) performed by the same physician at baseline and after 3, 6 and 12 months. Chest high-resolution computed tomography (HRCT) and pulmonary function tests (PFTs) and single-breath diffusing capacity were performed at baseline, after 6 and 12 months. The assessment of the extension of pulmonary fibrosis (PF) was analysed with the semiquantitative Warrick score and with the OsiriX quantitative computerized analysis. Data were analysed by Friedman test (GraphPadPrism V5).
Results 18 SSc patients were enrolled (M/F: 8/10, median age 51y, median disease 1 y, diffuse SSc 9, limited SSc 9). Three patients withdrew from the study: one was lost to follow-up, one had a minor infusion reaction which led to RTX discontinuation and one died for different causes. The analysis includes all 15 of 18 patients who completed 12 months of follow-up. The mRSS showed a statistically significant improvement (p**=0,0036), more remarkable in patients with diffuse cutaneous SSc. Concerning PFTs there was a statistically significant increase of FVC (p**=0,0093), FEV1 (p**=0,0061), with stable values of DLCO (p=0,3375). The HRCT scan showed an improvement statistically significant evaluated with analysis by OsiriX (p*=0,0331), while the Warrick score showed a not significant trend toward improvement. No serious adverse events were observed during the follow-up. In two patients the MMF dose was reduced for mild neutropenia.
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