Rituximab and Cyclophosphamide in Antisynthetase Syndrome-related Interstitial Lung Disease: An Observational Retrospective Study.

Abstract

Antisynthetase syndrome (AS)-related interstitial lung disease (ILD) has a poor prognosis. Intravenous cyclophosphamide (IV CYC) and rituximab (RTX) are the main treatments currently used for moderate to severe ILD. Here, we compare the efficacy of CYC followed by standard immunosuppressive treatment (IST) versus RTX in AS-related ILD. This observational retrospective study was conducted between 2003 and 2016 in 3 tertiary care centers. All patients with AS-related ILD and treated with CYC or RTX with at least 6 months of follow-up were included. Pulmonary progression-free survival (PFS), defined according to the American Thoracic Society guidelines, was assessed at 6 months and 2 years. All severe adverse events (AE) were recorded. Sixty-two patients were included. Thirty-four patients received 2-12 monthly IV CYC pulses, followed by standard IST in 30 cases (88%). The RTX group included 28 patients. Following the initial Day 1 to Day 15 infusions, RTX was repeated every 6 months in 26 cases (93%) and 15 patients (54%) concomitantly received another IST. The median steroid dose was similar between both groups. Although RTX and CYC demonstrated similar PFS at 6 months (92% vs 85%, respectively), RTX was superior at 2 years (HR 0.263, 95% CI 0.094-0.732, <i>P</i> = 0.011). Interestingly, lower diffusing lung capacity for carbon monoxide (DLCO) at baseline was independently predictive of poor 2-year PFS [0.965 (0.936-0.995), <i>P</i> = 0.023]. Forced vital capacity and DLCO improved in both groups without significant differences. Serious AE were similar in both groups. Despite similar PFS at 6 months, RTX was associated with a better 2-year PFS compared to CYC in patients with AS-related ILD.