Background The Antisynthetase syndrome (ASS) has a high frequency of interstitial lung disease (ILD) leading to increased morbidity and thereby needs for aggressive immunotherapy .
Objectives To evaluate efficacy and safety with Rituximab-treatment (Rtx) in a cohort of ASS patients with severe lung disease.
Methods Patients from a single referral center diagnosed between 1994-2013 with a positive serologic test of antisynthetase antibodies, ILD and/or myositis were defined as ASS (N=109). Patient data and pulmonary function tests (PFT;s) including forced vital capacity (FVC), forced expiratory volume in one second (FEV 1) and diffusing capacity of the lung for Carbon monoxide (DLCO) were retrospectively collected from medical reports. Severe lung disease was defined as FVC <70% of predicted, and/or DLCO <60% of predicted, and/or patients who needed mechanical respiratory support. Long-time was defined as >12 months, and serious adverse events (SAE;s) as events requiring hospitalization within three months after the last Rtx-infusion. To evaluate statistical significance (p<0.05), Wilcoxon signed-rank test was used.
Results In total, 33 patients were treated with Rtx, with a median follow-up from first Rtx of 35 months (3-118). Time from onset of first ASS symptom to first Rtx treatment varied between 1-350 months (median 24 months). Mean number of Rtx-treatment was 2.4 (1-11). Treatment-indication was in 29 patients severe lung-disease, two arthritis, and one lymphoma and myositis respectively. 5/29 patients with severe lung disease had less than 12 months follow-up from first Rtx, leaving 24 patients eligible for the study. None of the patients were treated with Rtx as monotherapy but 8/24 patients did not receive any other treatment prior to Rtx. Rtx treatment was given as one infusion à 1000mg day 0 and 14 except in three patients. At the first Rtx treatment median % predicted FVC was 58 (15-60) and at follow-up 73 (38-105), an increase of 26% (p<0.005). Median % predicted FEV1 increased with 22% from 58 (35-107) to 71 (31-115) (p<0.018). The increase in median % predicted DLCO was 17%, from 41 (15-60) to 48 (15-84) (p<0.025). Six patients responded with >40% increase in each test. These six patients were all treated with Rtx less than a year after the onset of symptoms (2-12 months). In 12/33 cases the steroid-treatment could be reduced from >10 mg daily to <10 mg daily. SAE;s occured in 7/33 patients, in 6/7 infections, in one a purpural rash. All SAE;s were in the severe lung disease group. 6/33 patients died during the observation period, all with severe lung disease.
Conclusions In this retrospective study of 24 Rtx-treated ASS patients with severe lung disease and a median observation time of 35 months there was an increase in FVC, FEV1 and DLCO of 26, 22 and 17%, respectively. Although all patients used other concomitant immuno-therapy the results indicate that Rtx could be an option in treating ASS-patients with severe lung disease. Patients with disease duration <12 months had the highest response-rate. Attention should be given to SAE;s, especially infections. Larger randomized controlled trials are warranted.
Marie I, Josse S, Hatron PY, Dominique S, Hachulla E, Janvresse A et al. Interstitial lung disease in anti-Jo1 patients with antisynthetase syndrome. Arthritis Care Res (Hoboken). 2013 May; 65(5):800-8.
Disclosure of Interest None declared