Immunoglobulin levels and infection risk with rituximab induction for anti-neutrophil cytoplasmic antibody-associated vasculitis

Background: Rituximab (RTX), a B cell-depleting anti-CD20 monoclonal antibody, is approved for treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Low immunoglobulin (Ig) levels have been observed surrounding RTX treatment. The association between the degree of Ig deficiency and infection risk is unclear in AAV patients.

Methods: AAV patients treated with RTX for remission induction at a single center (2005-15) with serum Ig measurements were included. Patient characteristics; serum IgG, IgM and IgA levels and occurrence of infections were collected retrospectively. Low IgG was defined as mild (376-749 mg/dL) or severe (>375 mg/dL). Logistic regression models were adjusted for age at RTX administration, estimated glomerular filtration rate (eGFR) and race to examine the association of degree and type of Ig deficiency and infection risk.

Results: Our cohort of 30 patients had a mean age of 63 (SD 7) years, 23 were women, 16 had granulomatosis with polyangiitis and 13 were PR3 ANCA positive. Nine patients received concomitant cyclophosphamide. The mean IgG level was 625 mg/dL (SD 289), mean IgM level was 55 mg/dL (SD 41) and mean IgA level was 133 mg/dL (SD 79). In this cohort, 20 patients had low serum IgG levels (<750 mg/dL) following RTX treatment. During the follow-up period, four individuals developed infections requiring hospitalization. In unadjusted logistic regression analysis, an IgG level ≤ 375 mg/dL was associated with 23 times higher odds of hospitalized infection [95% confidence interval (CI) 1.8-298.4; P = 0.02]. After adjustment for age, race and eGFR, results were similar [odds ratio (OR) 21.1 (95% CI 1.1-404.1) P = 0.04]. Low IgA was also associated with an increased risk of infections requiring hospitalization after adjusting for age, race and eGFR [OR 24.6 (95% CI 1.5-799.5) P = 0.03]. Low IgM was not associated with a higher risk of infections requiring hospitalization.

Conclusions: Severe hypogammaglobulinemia was associated with increased odds of infection requiring hospitalization in this cohort. Further investigation is warranted given our study is limited by small sample size, concomitant cyclophosphamide use and variable timing of Ig measurement.