Effectiveness and safety of rituximab across the four phenotypes of IgG4-related disease: a European multi-center cohort study.

Abstract

Assess relative effectiveness and safety of rituximab (RTX) across the four phenotypes of IgG4-related disease (IgG4-RD). We included phenotypically defined adult IgG4-RD patients treated with RTX +/- glucocorticoids (GC) who had evaluable data at 6 months on the composite primary outcome, which included: (i) treatment response (>= 2-point decline in responder index (RI)); (ii) absence of flare; and (iii) GC dose <= 7.5 mg prednisolone. Additional assessments at 6 and 12 months included remission (RI = 0 and prednisolone <= 7.5 mg), rate of infections and infusion reactions. Descriptive statistics and logistic regression were applied. We included 115 patients (74.8 % male, 86.1 % Caucasian) of whom 33 (28.7 %) had pancreato-hepato-biliary disease, 22 (19.1 %) retroperitoneal and aortic disease, 19 (16.5 %) head and neck-limited disease and 41 (35.7 %) Mikulicz' and systemic disease. The primary outcome was met by 80 patients (69.9 %) with no significant difference across phenotypes. Remission rate at 6 months was lower in retroperitoneal and aortic disease (4.5 %) than in the other phenotypes (18.2-36.6 %, p = 0.025) while the head and neck-limited phenotype had higher flare rate at 12 months than the others (38.9 % vs. 4.8-25.0 %, p = 0.005). In multivariable models, higher baseline RI and lower serum IgG4 associated with the primary outcome (p < 0.05). In this multi-center study, effectiveness of RTX did not differ across phenotypes. Our data do, however, indicate post-RTX differences in remission rates and flare risk across the phenotypes, with potential implications for surveillance and maintenance therapy.