Background: IgG4-related disease (IgG4-RD) is a progressive, systemic, fibroinflammatory disease characterized by unpredictable and recurring flares, leading to organ damage and decreased quality of life. The disease can affect nearly any organ and there is no approved treatment for IgG4-RD, highlighting the critical unmet need for effective, broadly relevant treatments. Inebilizumab (INEB) is a humanised, glycoengineered, CD19-directed, monoclonal antibody that depletes B cells, including plasmablasts and some plasma cells, effectively in a targeted manner. MITIGATE (NCT04540497) is an international, randomised, blinded, placebo (PBO)-controlled Phase 3 trial that evaluates the safety and efficacy of INEB as treatment for IgG4-RD in various demographic subgroups.

Objectives: To evaluate the safety and efficacy of inebilizumab in various demographic subgroups of patients enrolled in the MITIGATE study.

Methods: Adult participants who met the ACR/EULAR Classification Criteria for IgG4-RD with a score ≥20 were enrolled in the study. Eligible participants had a history of multiorgan IgG4-RD and had experienced an IgG4-RD flare that required glucocorticoid treatment during the screening period. Participants were stratified by first or subsequent IgG4-RD manifestation (i.e., newly diagnosed vs recurrent) to account for potential differences in flare risk. Participants were randomised 1:1 to inebilizumab or placebo and were treated on day 1, day 15, and week 26 of the 1-year randomised controlled period (RCP). The primary endpoint was time to first adjudication committee (AC)-determined and investigator-treated IgG4-RD flare during the RCP. Key secondary endpoints included annualised flare rate during the RCP and the proportion of participants achieving flare-free, treatment-free complete remission or flare-free, corticosteroid-free complete remission at Week 52. Safety was evaluated.

Results: 135 participants were randomised and received at least one dose of INEB (n=68) or PBO (n=67). Baseline demographics were generally well balanced between the 2 treatment groups. Mean age was 58.2 years in the study, with 31.1% of participants aged 65 years or older. Overall, 34.8% of participants were female, consistent with the known epidemiology of IgG4-RD, which has a male predominance. A total of 46.7% of participants were Asian, 39.3% were White, and 7.4% did not report. The remaining 6.6% of participants consisted of Black, American Indian or Native Alaskan, native Hawaiian or other Pacific Islander, unknown or other races. INEB treatment significantly reduced the risk of flare relative to PBO regardless of age, sex, or race (Table 1), with each subgroup exhibiting a hazard ratio similar to the overall study population, and consistent trends were observed across all regions. Annualised flare rates were reduced by INEB relative to PBO in all demographic subgroups. Similar results were observed for all subgroups with sufficient representation for the proportion of participants achieving flare-free, treatment-free complete remission or flare-free, corticosteroid-free complete remission at Week 52 (Table 2). No subgroup exhibited safety findings that were substantially different from those observed in the overall population.

Conclusion: The MITIGATE trial demonstrated that participants across various demographic subgroups derived similar clinical benefits with INEB treatment, making INEB a potentially effective and broadly applicable treatment choice for patients with IgG4-RD.

REFERENCES: NIL.

Acknowledgements: Study and abstract were funded by Amgen Inc. with medical writing support provided by Ayven Davoudi, PharmD, Amgen Inc.

Disclosure of Interests: John H. Stone Amgen; argenx; Bristol-Myers Squibb; F. Hoffman-La Roche; IgG4ward! Foundation; Novartis, Q32 Bio; Sanofi; Sobi; Steritas; Zenas, National Institutes of Health, Emma L. Culver Amgen; Zenus, NIHR Oxford BRC, Arezou Khosroshahi Amgen, Wen Zhang Amgen, Kazuichi Okazaki Medpace, Yoshiya Tanaka Abbvie; Eisai; Chugai; Eli-Lilly; Behringer-Ingelheim; GlaxoSmithKline; Taisho; AstraZeneca; Daiichi-Sankyo; Gilead; Pfizer; UCB; Asahi-kasei; Astellas, Behringer-Ingelheim; Taisho; Chugai, Matthias Lohr: None declared, Nicolas Schleinitz Amgen, Xinxin Dong Amgen, Amgen, Melissa Rosen Amgen, Amgen, Sue Cheng Amgen, Amgen, Daniel Cimbora Amgen, Amgen.

© 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.