RISK OF SEVERE INFECTIONS ASSOCIATED WITH IMMUNOGLOBULIN DEFICIENCY UNDER RITUXIMAB THERAPY IN IMMUNE MEDIATED INFLAMMATORY DISEASES
Authors: Rempenault C et al.
Literature data on the increased risk of severe infection regarding hypogammaglobulinaemia related to Rituximab (RTX) in immune mediated rheumatic diseases (IMID) are controversial and sparse. In this observational, retrospective single-center study patients with at least one infusion of RTX between January 1 and December 31 2017 were included. 307 patients treated for an IMID (rheumatoid arthritis, systemic lupus erythematosus, ANCA-associated vasculitis, primary Sjögren’s syndrome, inflammatory myopathy, scleroderma, mixt connective diseases, cryoglobulinemia vasculitis and overlap syndrome) with at least one Ig assay performed during follow-up were analyzed. Patients were followed-up at least 12 months after the last infusion of RTX or until the occurrence of a severe infection or death occurring within 12 months after the last infusion of RTX. Ig deficiency was defined as a rate of IgG, and/or IgA and/or IgM lower than the laboratory threshold.
29 (9,4%) had prevalent Ig deficiency. 68 patients (22,0%) acquired an Ig deficiency after the first infusion of RTX. Forty-three patients (14,3%) developed a severe infection within 12 months after the last infusion of RTX. Severe infections occurred more frequently in patients with prevalent Ig deficiency but without any statistical difference to patients with normal Ig level. In a time-dependent analysis, Ig deficiency in patients treated with RTX, whether acquired or prevalent, was not associated with an increased risk of severe infection (adjusted HR 1.04 [0.5-2.3], p=0.92). In multivariate analysis, only chronic pulmonary disease, a higher daily dose of glucocorticoids and a higher mean DAS28-CRP during follow-up were associated with an increased risk of severe infection.
This study from France didn’t show an increased risk of severe infection in RTX-induced Ig deficiency. In case of prevalent or acquired Ig deficiency, RTX management should be discussed on a case-by-case basis, according to an individual assessment of the infectious risk, especially when glucocorticoid therapy is used and chronic lung diseases are present. Therefore, Ig substitution should be given individually and only in patients with other risk factors for severe infections.