Dramatic regression of mass-forming gastric IgG4-related disease with inebilizumab: a case report

Abstract Background Gastric immunoglobulin G4-related disease (IgG4-RD) is exceedingly rare, with fewer than 50 cases reported worldwide. Its mass-forming presentation frequently mimics malignancy, leading to high rates of unnecessary surgical resection. Inebilizumab, a CD19-directed monoclonal antibody and the first FDA-approved therapy for IgG4-RD, has not previously been described in gastric IgG4-RD. We report the first case of mass-forming gastric IgG4-RD treated with inebilizumab, achieving clinical, endoscopic, and histologic remission without surgical intervention. Case presentation A 52-year-old man with chronic hypereosinophilia, nonischemic cardiomyopathy, and multisystem inflammatory disease presented with symptomatic anemia and a 2 cm gastric antral mass identified on CT imaging. Endoscopy revealed an antral mass, highly suspicious for malignancy. Initial biopsies showed Helicobacter pylori associated chronic active gastritis without definitive malignancy. Repeat sampling after H. pylori eradication demonstrated dense transmural lymphoplasmacytic and eosinophilic infiltration with 225 IgG4⁺ plasma cells per high-power field, an IgG4/IgG ratio of 37.5%, and a markedly elevated serum IgG4 of 1,245 mg/dL, establishing the diagnosis of gastric IgG4-RD. Concurrent lung biopsy confirmed multisystem involvement. The patient was initiated on inebilizumab. Within six weeks, follow-up endoscopy demonstrated significant resolution of the gastric mass with histologic remission (IgG4/IgG ratio < 10%), and six-month follow-up revealed near-complete resolution of the gastric abnormalities. Conclusions This case demonstrates that CD19-targeted B-cell depletion with inebilizumab can induce rapid, profound remission in gastric IgG4-RD, obviating the need for gastrectomy and chronic glucocorticoid therapy. These findings support early consideration of IgG4-RD in the differential diagnosis of mass-forming gastric lesions and highlight the transformative potential of mechanism-based therapy in this diagnostically challenging condition.