Rituximab-induced hypogammaglobulinemia in childhood nephrotic syndrome: a systematic review and meta-analysis

Rituximab, a chimeric anti-CD20 monoclonal antibody, is commonly used for complicated pediatric nephrotic syndrome (e.g., steroid-dependent or frequently relapsing disease). Post-rituximab hypogammaglobulinemia is a recognized adverse effect that may predispose to severe, including fatal, infections. We conducted a systematic review to estimate the incidence proportion of hypogammaglobulinemia after rituximab and the frequency of concomitant infections in children with nephrotic syndrome. We conducted a systematic review of five databases (1974-2024) for English-language studies enrolling children with nephrotic syndrome who received ≥ 1 dose of rituximab. Hypogammaglobulinemia was defined as an IgG concentration > 2 SD below the age-specific reference value. Of 2681 screened publications, 33 were eligible for meta-analysis. The pooled incidence of hypogammaglobulinemia in children with nephrotic syndrome receiving rituximab was 11.4% (95% CI, 6.4, 19.5). Patients who received rituximab were at increased risk of hypogammaglobulinemia with a risk ratio of 1.81 (95% CI, 1.46, 2.25; equivalent to 68 additional cases per 1000 patients). In 517 episodes of hypogammaglobulinemia, 93 (18%) infections occurred, four of which were fatal.

Hypogammaglobulinemia is a common side effect of rituximab that can result in life-threatening infections. The risk of hypogammaglobulinemia and infections should be weighed against the effectiveness of rituximab for nephrotic syndrome management. Prospero registration: CRD42024536465.

• Rituximab, a chimeric anti-CD20 monoclonal antibody, is commonly used for complicated pediatric nephrotic syndrome. • Post-rituximab hypogammaglobulinemia is a recognized adverse effect that may predispose to severe, including fatal, infections; however, the magnitude of risk of poorly understood in pediatric population.

• The pooled incidence of hypogammaglobulinemia in children with nephrotic syndrome receiving rituximab was 11.4%. Rituximab exposure was associated with a significantly higher risk of hypogammaglobulinemia compared with children not receiving rituximab (risk ratio 1.81). • In 517 episodes of hypogammaglobulinemia, 93 (18%) infections occurred, four of which were fatal.