Obexelimab in IgG4-related disease: B-cell inhibition as a novel therapeutic approach

IgG4-related disease is a chronic fibroinflammatory disease typically affecting multiple organs, such as the pancreas, liver, bile ducts, kidneys, and salivary and lacrimal glands. 1 Stone JH Zen Y Deshpande V IgG4-related disease. N Engl J Med. 2012; 366: 539-551 Crossref PubMed Scopus (1971) Google Scholar IgG4-related disease is rare and has a high number of unmet needs, including a paucity of approved therapies. 2 Iaccarino L Talarico R Scire CA et al. IgG4-related diseases: state of the art on clinical practice guidelines. RMD Open. 2018; 4e000787 Google Scholar This disease is frequently associated with a tendency to mass forming, which might result in tissue-destructive lesions with subsequent organ dysfunction or organ failure if not intensely treated. Although nearly all patients initially respond to glucocorticoid therapy, most patients will relapse or have flares within a few months of discontinuing treatment, requiring rescue therapy. Immunomodulatory drugs can be used in the hope of reducing glucocorticoid toxicity, but evidence for their efficacy in these patients is scarce. 3 Tanaka Y Stone JH Perspectives on current and emerging therapies for immunoglobulin G4-related disease. Mod Rheumatol. 2023; 33: 229-236 Crossref Scopus (0) Google Scholar Hence, development of targeted biological therapies is highly appreciated, and innovation and drug development in this area are much needed. Evaluation of the safety, efficacy, and mechanism of action of obexelimab for the treatment of patients with IgG4-related disease: an open-label, single-arm, single centre, phase 2 pilot trialAll patients except for one had clinical responses to obexelimab treatment. Both reductions in circulating B cells without evidence of apoptosis during obexelimab treatment and their rapid rebound after treatment discontinuation suggest that obexelimab might lead to B-cell sequestration in lymphoid organs or the bone marrow. These results support the continued development of obexelimab for the treatment of IgG4-related disease. Full-Text PDF