Background Antisynthetase syndrome (ASS) is a severe variant of idiopathic inflammatory myopathies. Unfavorable prognosis of this disease is associated with interstitial lung disease (ILD). Conventional treatment with glucocorticoids (GC) and cytotoxic drugs often does not provide sufficient improvement in such patients so addition of biologic agents is an interesting possibility.
Objectives To assess efficacy and tolerability of rituximab (RTM) in patients with ASS.
Methods RTM was administered to the patients admitted to the Institute of Rheumatology from 2009 to 2013. Manual muscle testing (MMT), dyspnea assessment according to NYHA, creatinkinase (CK) and anti-Jo-1 antibodies (anti-Jo-1) assay; forced vital capacity (FVC) and carbon monoxide diffusion capacity (DLCO) were performed at baseline in 17 and every 6 months thereafter in 12 cases. High-resolution computed tomography (HRCT) scanning of the chest at baseline was performed in 18 and after 6-12 months – in 13 patients.
Results 18 patients with ASS (16 female and 2 male, medianan age 50 [44;56], medianan disease duration 24 months [7;108]) were included. 14 from them had decreased MMT value and class 1-2 NYHA dyspnea was present in 17. 11 patients were positive for anti-Jo-1 and 8 had elevated CK level. HRCT showed ILD signs (including ground glass opacities) in all cases. FVC<80% was revealed in 9 and DLCO<80% - in 16 patients. All patients received glucocorticoids (GC) 10-90 mg/day equivalent to prednisolone, 5 were treated with cyclophosphamide 600-2000 mg/month, 2 – with mycophenolate mofetil 2 g/day. 5 patients received 2 infusions of 1000 mg RTM at days 0 and 14, 12 received 2 doses of 500 mg and 1 – 1000 mg and 500 mg. Later 6 patients received 1-5 repeated courses of RTM with 2 infusions of 500 mg. 6 months after the first RTM infusion MMT value normalized in 5 and increased in 3 cases. Dyspnea and CK level decreased in all and anti-Jo-1 level – in 11 patients. 7 patients displayed >10% improvement in FVC and 6 had >10% better DLCO values. For the rest pulmonary tests results remained stable. 12 months after treatment regression of ground glass attenuation on HRCT was achieved in 6 cases. In 5 patients lung changes remained stable and in 2 – increased. 12 patients were able to decrease GC dose. Most favorable results were achieved in 2 patients with short duration of the disease. 5 severe infections requiring hospitalization developed after treatment with RTM in 4 patients (severe pneumonia in 3, candidosis in 1, and sepsis with meningitis in 1 case). 2 from them died. All these patients received intermediate or high doses of GC. 6 patients had less severe infections (1- bronchopneumonia, 1 – exacerbation of chronic pyelonephritis, 1 – sinuitis, 1 – panaris, 3 – urinary infection and 1 – genital herpes).
Conclusions Treatment with RTM allows to control successfully ILD in patients with ASS. The best results can be achieved on early stage of the disease. High disease activity, high and intermediate GC doses and severe ILD should probably be considered as risk factors of severe infections in patients with idiopathic inflammatory myopathies receving RTM. The risk of infection development is highest 2-3 monthes after the first infusion of RTM.
Disclosure of Interest None declared