AB0660 Long-term effect of combination therapy with rituximab and mycophenolic acid on cardiac manifestations, pulmonary function and skin fibrosis in systemic sclerosis

Abstract

BackgroundCardiac manifestations in systemic sclerosis (SSc) can be either due to the fibrotic and vascular process or secondary to pulmonary arterial hypertension (PAH), cardiac inflammation, or renal crisis. Despite being one of the leading causes of death in SSc, cardiac involvement and its therapeutic options have been poorly studied. According to the ACR/EULAR recommendations, therapy with cyclophosphamide (CP) is applied to patients with cardiac manifestations. However, in case of inadequate response to CP, there are no other therapeutics evaluated.ObjectivesThe aim of this retrospective analysis was to explore the efficacy of a therapy with rituximab and mycophenolic acid (MPA), especially in cases of CP failure or therapy induced cardiac toxicityMethods14 Patients with SSc and cardiac involvement (defined as troponin T elevation plus right- or left ventricular systolic or diastolic dysfunction, myocarditis, pericarditis, right heart failure secondary to PAH, or arrhythmias) were analysed. Two patients each showed concomitant myositis and rheumatoid arthritis, respectively. Twelve patients were initially treated with CP and two patients with methotrexate (MTX). Due to a disease progress (either cardiac involvement, skin fibrosis or lung function) a therapy with rituximab and MPA was initiated [1] These patients were followed for up to five years.ResultsBefore initiation of CP or MTX electrocardiogram showed arrhythmias (atrial fibrillation, conduction blocks, multifocal ventricular extrasystoles (VES)) in 9 patients. Echocardiography revealed abnormalities in 10 patients including reduced left-ventricular ejection fraction (LV-EF), diastolic dysfunction, mitral regurgitation, or aortic aneurysm. 3 patients had PAH, 2 patients were diagnosed with post capillary pulmonary hypertension. Cardiac MRI revealed signs of myocarditis in 4 patients. 4 patients required cardiac resynchronization therapy or pacemaker implantation. Moreover, body plethysmography showed a reduction in forced vital capacity (FVC) in 12 patients, suggestive of restrictive lung disease. Under therapy with CP 11 patients had suffered from disease progress, 1 patient developed relapsing pneumonias and the 2 patients with overlap rheumatoid arthritis developed cardiac disease manifestations on MTX monotherapy. Consequently, rituximab 1000 mg q12weeks and MPA 1000 mg bid were initiated. Under this combination troponin T decreased in all patients (p=0.0002), LV-EF improved in 5, remained normal in 7 and deteriorated in 2 patients. The rate of VES improved in 8 patients. In one patient, myocarditis resolved completely (MRI). Moreover, pulmonary artery systolic pressure, measured by echocardiography, improved in all patients diagnosed with PAH under stable therapy. The modified Rodnan skin score improved in all patients, FVC improved in 7 patients, remained stable in 6 and decreased in the patient with overlap myositis. Rituximab infusions could be extended (1000 mg q24weeks) after 24-36 months of treatment in 11 patients. All patients showed peripheral blood depletion of B cells without noticed severe IgG deficiency. While 11 patients did not develop severe complications 2 patients died during follow-up of pneumonia and cardiogenic shock (overlap myositis), respectively and one patient developed a relapse of lung cancer with cerebral metastasis.ConclusionTherapy with rituximab and MPA is a promising alternative. However, its use requires risk stratification of patients with respect to adverse side effects which needs to be explored in future studies.