Rituximab-Induced Hypogammaglobulinemia and Infections in AQP4 and MOG Antibody–Associated Diseases

Abstract

ObjectiveTo determine the potential association between infections and rituximab (RTX)-induced hypogammaglobulinemia among patients with CNS inflammatory diseases.MethodsWe included in a prospective observational study all consecutive adults with aquaporin 4 (AQP4) or myelin oligodendrocyte glycoprotein (MOG) antibody–positive disorders treated with RTX. Dosing schedule was adapted to memory B-cell measurement.ResultsWe included 48 patients (mean age 47 [SD: 14] years; 77% females; 31 AQP4 positive and 17 MOG positive). The median follow-up was 3.6 years (range: 0.9–8.1 years). The median number of RTX infusions was 8 (range: 2–14). The median dosing interval was 6 months (range: 1.7–13.7 months). Sixty-seven symptomatic infections (SIs) were observed in 26 of 48 (54%) patients, including 13 severe infections in 9 (19%). Urinary and lower respiratory tract infections were the most frequent, representing 42% and 21% of SI. At RTX onset, the immunoglobulin G (IgG) level was abnormal in 3 of 48 (6%) patients. After RTX, 15 (31%), 11 (23%), 3 (6%), and 0 of 48 patients showed sustained IgG level <7, <6, <4, and <2 g/L, respectively. On multivariate Cox proportional hazards analysis, the main variables explaining the risk of SI were the presence of urinary tract dysfunction (hazard ratio [HR] = 34, 95% CI 4–262, p < 0.001), the dosing intervals (HR = 0.98, 95% CI 0.97–0.99, p < 0.001), and the interaction between IgG level and urinary tract dysfunction (HR = 0.67, 95% CI 0.53–0.85, p < 0.005). IgG level <6 g/L during RTX was associated with male sex (HR = 4, 95% CI 1.4–11.4, p < 0.01) and previous immunosuppression (HR = 3.4, 95% CI 1.2–10, p < 0.05).ConclusionsRTX used as maintenance therapy in CNS inflammatory diseases is frequently associated with reduced IgG level and increases the infection risk of the most vulnerable patients.

Anti-CD20 therapies decrease humoral immune response to SARS-CoV-2 in patients with multiple sclerosis or neuromyelitis optica spectrum disorders

“…Several studies have shown that patients with MS or NMO-SD taking anti-CD20 have an increased risk of infection, 23 possibly related to hypogammaglobulinemia. 24 In our cohort, total IgG level tended to be associated with anti-S IgG titre and anti-SARS-CoV-2 Ig positivity. The postinfectious immune response has generally been poorly studied in patients with MS, contrarily to the postvaccination humoral response.…”

COVID-19 in Patients With Neuromyelitis Optica Spectrum Disorders and Myelin Oligodendrocyte Glycoprotein Antibody Disease in North America

“… 13 , 14 Moreover, it may be reasonable in some patients (e.g., NMOSD with medical comorbidities and NMOSD with hypogammaglobulinemia) to consider tailoring their treatment regimen in hopes to minimize infectious risks. 15 …”

Hypogammaglobulinemia and Infections in Patients With Multiple Sclerosis Treated With Rituximab

“…3 Treatment-induced hypogammaglobulinemia contributes to infections in patients with rheumatologic and hematologic diseases and neuromyelitis optica disorders treated with B-cell depleting therapy. [4][5][6] We do not know whether treatment-induced hypogammaglobulinemia could also be involved and be harmful in patients with MS (PwMS), who are generally younger and with fewer comorbidities than those with other diseases. Pivotal studies 1,7 have demonstrated that hypogammaglobulinemia is infrequent in PwMS during the first years of treatment, but little is known about its potential medium-term incidence in nonselected patients nor about its interaction with the risk of infection.…”