Background/Purpose: Rituximab (RTX) is an effective immunosuppressive therapy for many autoimmune diseases. Secondary hypogammaglobulinemia (hypoIg) can occur mainly after repeated cycles of RTX. The risk of infection in these patients has been shown to be higher in some studies, especially with secondary hypoIgM. Our objectives are to determine whether low IgG or IgM levels associate with infection in RTX treated patients.

Methods: Retrospective observational study of patients with autoimmune diseases from a single center, treated with RTX (2x1000mg 2 weeks apart) between 2010-2017. Patients that did not complete one full RTX cycle were excluded. Exposures were demographical characteristics; previous/concomitant immunosuppressants and peripheral B cell CD19+ count. Outcomes were serum Ig levels (IgM, IgG and IgA) at baseline and 4-6 months after each cycle, hypoIg and serious infections (defined as requiring hospitalization and/or intravenous treatment). Fisher exact test was used to compare dichotomous variables; Wilcoxon rank sum test to compare continuous variables with skewed distributions; logistic regression for normal distributed continuous variables.

Results: 41 patients were included with a median age of 50.9 years (IQR 37.4, 64.9); median number of cycles of 4. Most patients had systemic lupus erythematous (36.6%), rheumatoid arthritis (14.6%) and myasthenia gravis (14.6%). During all treatment period 18 patients (43.9%) developed hypoIgG, 22 (53.7%) hypoIgM and none hipoIgA. Lower baseline IgG and IgM levels were associated with hypoIgG (p<0.001) and hypoIgM (p=0.03), respectively. Moreover, after each RTX cycle median IgM levels tend to decrease (p<0.001 until the 3^rd cycle), while median IgG levels tend to remain stable after the 1^st cycle. Incidence of hypoIgG was lower in patients treated hydroxychloroquine (HCQ) (p=0.01). Other immunosuppressive therapy and clinical characteristics did not associate with hypoIg. 13 patients had a serious infection (incidence rate of infection of 19.2/100 patients-year). Incidence of infection was higher in elderly patients (p=0.02) and lower in patients treated with HCQ (p=0.02), and did not associate with hypoIgG or hypoIgM. Lower median levels of IgG were associated with a higher incidence of infection after the 2^nd (p=0.03) and the 3^rd (p=0.02) cycles. Analyzing the variation of IgG levels between baseline and each cycle, there was a tendency towards the occurrence of infection in relation with a higher % of negative variation of IgG levels, especially after the 3^rd cycle, although not statistically significant (p=0.06).

Conclusion: a higher incidence of serious infections did not associate with low absolute IgM or IgG titers, but with the percentage of reduction of IgG levels, and not IgM, from baseline and each treatment. This can have a clinical impact in the decision to stop RTX treatment based on safety. HCQ showed a protective role for infection in patients treated with RTX, which can be explored in larger prospective studies.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/hypogammaglobulinemia-and-infection-risk-in-patients-treated-with-rituximab/