A protocol for targeted B-lymphocyte depletion for the treatment of IgG4-related disease

Abstract

Objectives: To determine the clinical outcomes of patients with immunoglobulin 4-related disease (IgG4-RD) treated with a defined B-cell depletion protocol using rituximab.

Methods: Patients were included if they had (i) an IgG4-RD diagnosis at Imperial College Healthcare NHS Trust between February 2017 and October 2022, and (ii) >9 months of follow-up data available following the first rituximab dose. The rituximab protocol targeted B-cell depletion to <10 cells/microliter for a maintenance period of two years. Electronic records were used to define patient demographics, serological and radiological variables and treatment responses according to the IgG4-RD responder index (RI).

Results: Forty-five patients received induction treatment with rituximab. Two patients had insufficient follow-up data for outcome analysis. All patients responded to rituximab therapy according to the IgG4-RD RI. Most patients (25/43, 58%) were also treated with low-dose glucocorticoids at the time of rituximab induction (median prednisolone dose 5 mg daily) and 4/25 (16%) remained on prednisolone at two years (median prednisolone dose 5 mg daily). Disease flares occurred in 11/43 (26%) patients; 9/11 flares occurred in the presence of B-cell repopulation; 2/11 (18.1%) flares occurred in the absence of B-cell repopulation (>10 cells/uL). All flares re-treated with rituximab (7/7, 100%) responded positively.

Conclusion: Rituximab administration targeting B-cell depletion for a two-year period is an effective treatment strategy for IgG4-RD and can limit the cumulative glucocorticoid exposure. Flares are uncommon and typically occur in the setting of B-cell repopulation, with good clinical responses to further rituximab administration.

Keywords: IgG4-RD; anti-CD20; immunosuppression; inflammation; multisystem disease; protocol; retroperitoneal fibrosis; rheumatology; rituximab.