AB0278 OFF-LABEL RITUXIMAB FOR SYSTEMIC AUTOIMMUNE DISEASES: A CASE SERIES FROM A THIRD LEVEL HOSPITAL DURING A 5 YEAR- PERIOD

Abstract

Background:Rituximab (RTX) is a drug composed of chimeric monoclonal antibodies against the CD20 protein that leads to B cell lymphocyte depletion and is currently licensed for rheumatoid arthritis. There is growing evidence of off-label use of rituximab for severe and refractory systemic autoimmune diseases (SAD).Objectives:Analysing the clinical effectiveness of RTX for SADs such as vasculitis (VS), systemic lupus erythematosus (SLE), systemic sclerosis (SS), primary sjögren syndrome (pSS), necrotizing myopathy (NM) and dermatomyositis (DM) in a rheumatology outpatient clinic in a third level hospital during a 5 year-period (2015 –2020).Methods:We conducted a retrospective analysis of patients with SAD treated with RTX in the last 5 years. We evaluated demographic and clinical data, indication for RXT, previous treatments, cumulative dose of rituximab and corticosteroids, clinical response, and the presence of adverse events. We considered follow-up period between the first and the last clinical evaluation. Clinical response was considered complete with symptom and analytical remission; incomplete with partial symptom or analytical response and no response if there was no symptom or analytical response.Results:35 patients were included (54% women, mean age 60.16 ±17 years). The diagnosis were: pSS (31.4%), SS (17%), SLE (17%), VS (20%), NM (8.8%) and DM (5.8%). Indications for treatment were pulmonary disease in 37% of cases, renal disease in 17%, articular manifestations in 11.4%, haematological manifestations in 14.3%, skin involvement in 8.8%, neurologic manifestations in 5.7% and myopathy in 5.8%. RTX was used after therapeutic failure with previous treatments in 80% (20% of which had receiving treatment with biological disease-modifying antirheumatic drugs) and as first line treatment in only 20% of the cases. After rituximab, 60% of patients had complete response, 17% partial response, and 20% nonresponding. Mean corticosteroid dose post-rituximab was significantly reduced by 60% in pSS (p 0.02), 65% in VS (p 0.03), 50% in SS (p 0.04) and NM (p 0.046). Five patients (14%) had infectious complications, 2 of which needed hospitalization. 7 patients (17%) discontinued therapy, 5 due to ineffectiveness (2 SLE, 1 NM, 1 DM and 1 SS) and 2 patients (14%) due to infectious complications (1 pSS and 1 VS). Patients underwent a median of 2 treatment cycle. The median follow-up after starting RTX was 48.5 (IQR 25.9-74.4) months.Table 1.Clinical characteristicspSSVSSLESSNMDM%31.4%20%17%17%8.8%5.8%Age (years)63.8 (19-73)63.5 (43-82)59.2 (43-78)65.8 (56-78)58.5 (54-63)48.5(26-52)Female100%71%50%66%50%50 %Duration of disease (months)80.5 (24-108)39 (12-60)38.4 (36-90)56.4 (14-96)69 (48-90)60 (25-82)Cumulative RTM dose (g/m2)2.5 (0.75-6)3.2 (0.5-8)1.4 (0.75-5)2.8 (0.5 – 7)1.2 (0.5 – 5)0.56 (0.38-0.75)Complete clinical response63%86%33%71%33%0%Incomplete response18%14%33%14%0%50%No response18%0%33%14%66%50%Glucocorticoid dose (mg/day)Before RTMX12.5 (5-20)21.3 (5-30)9 (0-15)9 (5-15)15 (7.5 – 25)15 (7.5 – 25)Glucocorticoid dose (mg/day)After RTX5 (2.5-15)7.5 (5-15)5 (2.5-15)4.5 (2.5-10)10 (7.5-25)12.5 (8 – 20)ImmunosuppressantsBefore RTX81%71%90%50%33%50%ImmunosuppressantsAfter RTX54%28%57%66%67%50%Severe infusion-related side effects including need for admission0%14%16%0%0%0%Other infusion-related side effects9%29%17%17%0%0%Conclusion:Treatment with RTX was very effective in SADs, particularly in VS, SS and pSS. Further studies are needed to clarify RTX efficacy and safety in SADs, as well as indications and optimal RTX regimens.