Background: Combination therapy with rituximab and belimumab is a novel treatment strategy for severe systemic lupus erythematosus (SLE) and lupus nephritis (LN). Phase 2 studies have shown promising results, although long-term data are currently lacking.

Objectives: To address this, we analyzed outcomes of patients with severe treatment-refractory SLE who previously participated in the phase 2 Synbiose study, with a particular focus on immunological parameters.

Methods: Eight patients continued belimumab treatment beyond the two-year duration of the original trial. We conducted a descriptive study to evaluate the course of treatment and immunological parameters over an extended follow-up. Our analyses include blood cell counts, immunoglobulins, autoantibodies, complement markers, and clinical disease activity parameters. Additionally, we examined long-term effects on the B cell compartment employing high-sensitivity flow cytometry.

Results: Over a median follow-up period of 6, 8 years, six out of eight previously treatment-refractory patients maintained long-term clinical remission, while two experienced a major flare. Among those in remission, two patients achieved immunosuppression-free remission, and four continued belimumab. Long-term effects on humoral (auto-)immunity were a persistent decrease in IgM levels, while IgG normalized. Most patients maintained low autoantibody titers, and complement markers remained normal. On the cellular level, belimumab treatment after rituximab prevented B cell repopulation. Notably, patients exhibited a stable reduction of double negative B cells, irrespective of continuing or stopping belimumab.

Conclusion: Long-lasting remission was observed in SLE patients following combination treatment with rituximab and belimumab. We observed no significant hypogammaglobulinemia and, notably, persistent reduction of double negative B cells.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: Mieke van Schaik: None declared, Eline Arends: None declared, Marjolein Wetzels: None declared, Tineke Kraaij: None declared, Stephanie Verbruggen: None declared, Sandra van der Kooij: None declared, Sylvia Kamerling: None declared, Tom Huizinga: None declared, Robbert Goekoop: None declared, Cees van Kooten: None declared, Ton Rabelink: None declared, Y.K. Onno Teng Y.K.O.T. received consultancy fees from GlaxoSmithKline, GlaxoSmithKline provided belimumab and an unrestricted grant for the study described in this abstract.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.