PO:26:087 | Rituximab versus glucocorticoids for IgG4-related disease: a European retrospective multi-center study of 167 patients

Marco Lanzillotta¹, Jens Vikse², Elisabetta Goni³, Jasmin Mahajne¹, Veronica Batani¹, Lorenzo Dagna¹, Emanuel Della-Torre¹ | ¹Unit of Immunology, Rheumatology, Allergy, and Rare Disease, IRCCS Ospedale san Raffaele Milano, Italy; ²Department of Rheumatology, Stavanger University Hospital, Stavanger, Norway; ³Department of Medicine II, University Hospital, Ludwig Maximilian University Munich, Munich Germany

Aims. IgG4-related disease (IgG4-RD) is a relapsing remitting fibroinflammatory disorder that can affect virtually any organ system often requiring multiple treatment courses. This study aimed to compare the efficacy and safety of rituximab (RTX) versus glucocorticoids (GC) in patients with active, new-onset or relapsing IgG4-RD in a real-world European multi-center setting.

Materials and Methods. We conducted a retrospective observational study across three European referral centers—San Raffaele Scientific Institute in Milan (Italy), Oslo University Hospital (Norway), and LMU University Hospital in Munich (Germany). We included all patients treated with RTX (+/- GC) who had a subsequent follow-up of 6 months (RTX arm), and a comparator group of GC treated patients matched 2:1 based on sex, ethnicity and fulfillment of the 2019 ACR/EULAR classification criteria (GC arm). The primary composite endpoint, modeled after a 2015 open-label RTX trial, included: (i) clinical response (greater than 2-point decrease in IgG4-RD Responder Index [RI]), (ii) absence of flare, and (iii) GC dose lower than 7.5 mg at 6 months. Secondary endpoints included remission, flare rate, GC discontinuation, infection requiring hospitalization, and death. Logistic regression analyses were used to assess outcomes and predictors.

Results. A total of 167 patients were included: 115 (68.9%) in the RTX arm, 52 (31.1%) in the GC arm. Patients in the RTX arm were younger, with a higher baseline RI score, lower baseline GC dose, longer disease duration, and more often relapsing disease. The primary endpoint was met by 69.6% in the RTX group vs 63.5% in the GC group (p=0.435). Treatment response rates were similar (80.0% vs 78.8%), as were remission (24.3% vs 26.9%) and flare rates (9.6% vs 17.3%, p=0.154). Notably, RTX-treated patients were significantly more likely to discontinue GC within 6 months (47.0% vs 13.5%; OR 3.70, 95% CI 1.06–12.87, p=0.040). Higher baseline RI score was the strongest predictor of treatment response and primary endpoint achievement. Female sex and lower baseline GC dose also predicted GC discontinuation. The rate of infections requiring hospitalization was 9% in RTX arm and 11% in GC arm (p >0.05), and no deaths were reported. Infusion reactions occurred in 12% of RTX-treated patients and were mostly mild.

Conclusions. In this large, multi-center European study, RTX showed comparable short-term efficacy to GC despite being used in patients with more severe or relapsing IgG4-RD. Importantly, RTX enabled higher rate of GC discontinuation at 6 months, underscoring its potential as a GC-sparing strategy. These real-world data support the ongoing use of RTX in clinical practice, particularly as GC toxicity remains a major concern in IgG4-RD, especially for patients with pancreatic involvement. While randomized head-to-head trials remain ideal, our findings provide valuable guidance for treatment decisions in everyday clinical settings.