Inebilizumab, a novel anti-CD19 antibody for treatment of IgG4-related disease: an overview from clinical trials

INTRODUCTION: IgG4-related disease (RD) is characterized by multiple organ inflammation and enlargement, nodular or hypertrophic lesions, significant infiltration of B cells and IgG4-positive plasma cells, and characteristic fibrosis on histology. It causes diverse organ damage, decreased quality of life, and increased mortality. AREAS COVERED: Treatment typically involves systemic glucocorticoids, which show good initial response rates. However, treatment resistance and flares upon dose reduction or discontinuation are commonly observed. Although the toxicity of glucocorticoids gathers attention, no glucocorticoid-sparing agent has been approved. The involvement of the immune system, including B cells and plasmacytes, in pathological processes has been demonstrated, and the Phase III MITIGATE trial using an anti-CD19 antibody inebilizumab met its primary endpoint, with inebilizumab recently receiving the first regulatory approval for treatment of IgG4-RD in the United States, the European Union, Japan, and others. EXPERT OPINION: This article provides an overview of advances in treatment strategies for IgG4-RD, shedding light upon the characteristics of inebilizumab and results of the clinical trials. Various targeted therapies under the development are expected to overcome limitations in safety and efficacy of glucocorticoids and to reduce risk of organ damage and fibrosis.