Background:The anti-CD20 antibody rituximab (RTX) is approved for the treatment of rheumatoid arthritis (RA) and ANCA-associated vasculitis (AAV). In addition, RTX is used in a wide range of autoimmune diseases. Belimumab (BEL) is an anti-BAFF antibody approved for the treatment of non-renal systemic lupus erythematosus (SLE) in Europe. These agents are generally well-tolerated but severe adverse events (AEs) can occur. The frequency of and factors associated with AEs are currently unknown.Objectives:To identify adverse events with the use of B-cell directed therapies in a large population of RA, AAV, and SLE.Methods:This is a single-center retrospective cohort study using routine clinical data over a ten-year period (2010-2020). We recorded epidemiological and clinical data of patients receiving either BEL or RTX. Data included age, gender, type of disease, number and efficacy of infusions, patient-years and concomitant treatment. Patient records were screened for AEs, such as infections, anaphylaxis, occurrence of malignant disease, laboratory abnormalities and immunoglobulin (Ig) deficiency. Between group comparisons were performed.Results:Database screening yielded 445 patients treated with RTX and 23 with BEL. After exclusion of patients with incomplete data, 425 RTX and 23 BEL patients were analyzed.Our preliminary analysis of a sample of 60 of these 448 patients (184 patient-years) resulted in 43 patients (72%) with RA, 8 patients with AAV (13%), 5 patients with a renal disease, and 4 patients with mixed connective tissue disease, as well 23 SLE patients. 46 (77%) were female. In RA, a median of 13 treatments of 1000 mg were administered, corresponding to 3.37 patient-years per patient. Primary non-response occurred in 2 patients, secondary non-response in 13 patients. For AAV, a median of 8.4 treatments were given (3.3 patient-years), no treatment failure was detected. SLE patients received a median of 15 treatments.15 patients had infectious complications during treatment, 11 needed treatment. Herpes zoster infection occurred in 3 patients with RA. Three of the 8 patients with AAV had an infection requiring treatment. In SLE patients, only 2 developed infectious complications, and no Ig-deficiency occurred.Lymphopenia was the most common laboratory abnormality detected in 25 patients with RTX, 19 of whom had RA. Ig deficiency was common in RA, affecting 30% of patients. Deficiency of IgM and IgG was recognized in 5 patients each; 1 patient had low levels IgA.Neither the maintenance prednisolone dosage nor Ig deficiency were associated with risk for infection. However, lymphopenia appeared to be associated with risk for infection.Conclusion:Our preliminary data observe a 184 patient-year period. RTX and BEL were generally associated with few AEs. RA patients frequently had laboratory abnormalities (lymphopenia, Ig-deficiency) which did not necessarily translate to clinical events. Infections were more common in AAV, BEL was the best tolerated B-cell directed agent. Overall, our data are reassuring, but we suggest a more careful vigilance in AAV patients.Disclosure of Interests:Jan-Gerd Rademacher: None declared, Viktor Korendovych: None declared, PETER KORSTEN Speakers bureau: Abbvie, Sanofi Aventis, GSK, Chugai, Boehringer-Ingelheim, Novartis, Consultant of: Lilly, Gilead, Boehringer-Ingelheim, Novartis, GSK, Grant/research support from: GSK
Pharmacovigilance of Biopharmaceuticals in Rheumatic Diseases, Adverse Events, Evolution, and Perspective: An Overview