Hypogammaglobulinaemia in patients with ANCA-associated vasculitis treated with rituximab

This study aimed to characterize the occurrence of hypogammaglobulinaemia (HG) in rituximab (RTX)-treated patients with ANCA-associated vasculitis (AAV) in a population-based Swedish cohort.

Patients with incident AAV (1997-2019) in southern Sweden who received RTX for induction or maintenance therapy were included in this study. Medical records were reviewed to assess the incidence of HG (defined as total IgG < 6.7 g/L; mild 5-6.7, moderate 3-4.9, severe <3), as well as demographics, serology, and treatment history. Incidence rates and predictors of HG were analyzed. Follow-up was extended from the first RTX administration to the onset of HG, death, or the end of the study period (March 2023).

Eighty-four patients [51% female; granulomatosis with polyangiitis (GPA), n = 57; microscopic polyangiitis (MPA), n = 25; eosinophilic granulomatosis with polyangiitis (EGPA), n = 2] received RTX and were followed for a total of 236 person-years (py). HG occurred in 38 patients (45%), yielding an incidence rate of 16.1 (95%CI 11-21.2) per 100 py. A sensitivity analysis excluding 14 patients with preexisting HG identified 24 incident HG cases, corresponding to an incidence rate of 17.6 (95%CI 10.6-24.7) per 100 py. Among those who developed HG, the condition was mild in 26 (68%) patients, moderate in 10 (26%), and severe in two patients (5%). Baseline IgG levels were significantly lower in patients who subsequently developed HG, whereas age, clinical characteristics, and other laboratory findings did not differ between groups. Severe infections occurred in 23 patients (35%); five of these infections occurred after the onset of HG, and three occurred before HG onset. The median time to HG development was 3.5 (IQR 0.7-6) months. A lower baseline IgG level was identified as an independent predictor of HG (HR 0.85 per 1 g/L increase; 95%CI 0.76-0.95).

HG is a common complication in RTX-treated patients with AAV; however, in this cohort, it was not associated with an increased risk of severe infections. A low baseline IgG level was an independent predictor of subsequent HG development, underscoring the importance of close IgG monitoring both before and during RTX therapy.