Rituximab-associated hypogammaglobulinaemia in ANCA-associated vasculitis and connective tissue diseases: a longitudinal observational study

Abstract

Objectives: The burden of hypogammaglobulinaemia following rituximab (RTX) treatment in rheumatic diseases has not been fully elucidated yet. Our aim was to evaluate the frequency and predictors of hypogammaglobulinaemia in patients affected by ANCA-associated vasculitis (AAV) and connective tissue diseases (CTD).

Methods: We retrospectively reviewed prospectively collected data of patients receiving RTX. Immunoglobulins (Ig) levels and lymphocyte subsets were recorded at RTX administration and 3-6 months later. We assessed frequency of hypogammaglobulinaemia (serum IgG<6 g/L) and its related events. Univariate and multivariable analysis were performed using SPSS 20.0 package.

Results: Sixty-eight patients (30 AAV, 25 systemic lupus erythematosus, 9 systemic sclerosis and 4 idiopathic inflammatory myopathies) were treated with RTX (95 infusions, median 2 [2-6]). Following RTX, IgG<6 g/L were observed in 15/68 patients (15.8%), IgM<0.4 g/L in 28/68 (41%) and IgA<0.7 g/L in 7/68 (10.2%). Hypogammaglobulinaemia was more common in patients with AAV (p=0.008), short disease duration (p=0.001), low IgG levels at baseline (p=0.008), high cyclophosphamide exposure (p=0.018), high daily and cumulative prednisone dosage (p=0.001 and p=0.006). At multivariate analysis, cumulative cyclophosphamide dosage (OR 1.1 [1.0-1.3] p=0.045), daily prednisone intake >15mg (OR 9.5 [2.2-41.7] p=0.03) and IgG levels before RTX (OR 0.74 [0.59-0.93] p=0.009) were independent predictors of hypogammaglobulinaemia. Five patients experienced severe infections within 12 months, more frequently in those with IgG<6 g/L (26.7% vs 1.9%, p=0.007).

Conclusions: Hypogammaglobulinaemia following RTX is uncommon in AAV and CTD and is more likely in patients with high glucocorticoids and cyclophosphamide exposure and low IgG levels at baseline.