{"doi":"10.1056/nejmoa2012047","title":"Anti–Siglec-8 Antibody for Eosinophilic Gastritis and Duodenitis","abstract":"BACKGROUND: Eosinophilic gastritis and duodenitis are characterized by gastrointestinal mucosal eosinophilia, chronic symptoms, impaired quality of life, and a lack of adequate treatments. Mast-cell activity may contribute to the pathogenesis of the conditions. AK002 (lirentelimab) is an anti-Siglec-8 antibody that depletes eosinophils and inhibits mast cells and that has shown potential in animal models as a treatment for eosinophilic gastritis and duodenitis. METHODS: In this phase 2 trial, we randomly assigned adults who had symptomatic eosinophilic gastritis, eosinophilic duodenitis, or both conditions in a 1:1:1 ratio to receive four monthly infusions of low-dose AK002, high-dose AK002, or placebo. The primary end point was the change in gastrointestinal eosinophil count from baseline to 2 weeks after the final dose; to maximize statistical power, we evaluated this end point in the placebo group as compared with the combined AK002 group. Secondary end points were treatment response (>30% reduction in total symptom score and >75% reduction in gastrointestinal eosinophil count) and the change in total symptom score. RESULTS: Of the 65 patients who underwent randomization, 43 were assigned to receive AK002 and 22 were assigned to receive placebo. The mean percentage change in gastrointestinal eosinophil count was -86% in the combined AK002 group, as compared with 9% in the placebo group (least-squares mean difference, -98 percentage points; 95% confidence interval [CI], -121 to -76; P<0.001). Treatment response occurred in 63% of the patients who received AK002 and in 5% of the patients who received placebo (difference, 58 percentage points; 95% CI, 36 to 74; P<0.001). The mean change in total symptom score was -48% with AK002 and -22% with placebo (least-squares mean difference, -26 percentage points; 95% CI, -44 to -9; P = 0.004). Adverse events associated with AK002 were similar to those with placebo, with the exception of higher percentages of patients having mild-to-moderate infusion-related reactions with AK002 (60% in the combined AK002 group and 23% in the placebo group). CONCLUSIONS: In patients with eosinophilic gastritis or duodenitis, AK002 reduced gastrointestinal eosinophils and symptoms. Infusion-related reactions were more common with AK002 than with placebo. (Funded by Allakos; ENIGMA ClinicalTrials.gov number, NCT03496571.).","journal":"New England Journal of Medicine","year":2020,"id":49355,"datarank":3.839978682591724,"base_score":5.583496308781699,"endowment":5.583496308781699,"self_citation_contribution":0.837524446317255,"citation_network_contribution":3.002454236274469,"self_endowment_contribution":0.837524446317255,"citer_contribution":3.002454236274469,"corpus_percentile":null,"corpus_rank":null,"citation_count":265,"citer_count":100,"citers_with_citation_signal":100,"citers_with_endowment":100,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9571,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT03496571"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":237521,"name":"Kathryn A. Peterson","orcid":"0000-0003-1793-6027","position":1,"is_corresponding":false},{"id":237522,"name":"Joseph A. Murray","orcid":"0000-0003-1941-9090","position":2,"is_corresponding":false},{"id":237523,"name":"Gary W. Falk","orcid":"0000-0002-7143-1436","position":3,"is_corresponding":false},{"id":237524,"name":"Nirmala Gonsalves","orcid":"0000-0003-0722-6099","position":4,"is_corresponding":false},{"id":237525,"name":"Mirna Chehade","orcid":"0000-0002-7177-2791","position":5,"is_corresponding":false},{"id":237526,"name":"Robert M. Genta","orcid":"0000-0001-9482-4163","position":6,"is_corresponding":false},{"id":237527,"name":"John Leung","orcid":"0000-0003-4208-8955","position":7,"is_corresponding":false},{"id":237528,"name":"Paneez Khoury","orcid":"0000-0003-1800-0079","position":8,"is_corresponding":false},{"id":237529,"name":"Amy D. Klion","orcid":"0000-0002-4986-5326","position":9,"is_corresponding":false},{"id":239163,"name":"Sabine Hazan","orcid":null,"position":10,"is_corresponding":false},{"id":237530,"name":"Michael F. Vaezi","orcid":"0000-0003-3179-0212","position":11,"is_corresponding":false},{"id":237531,"name":"Adam C. Bledsoe","orcid":"0000-0002-6166-6661","position":12,"is_corresponding":false},{"id":237532,"name":"Sandy Durrani","orcid":"0000-0001-8311-596X","position":13,"is_corresponding":false},{"id":237533,"name":"Chao Wang","orcid":"0000-0002-0559-3015","position":14,"is_corresponding":false},{"id":239164,"name":"Camilla Shaw","orcid":null,"position":15,"is_corresponding":false},{"id":239165,"name":"Alan T. Chang","orcid":null,"position":16,"is_corresponding":false},{"id":237534,"name":"Bhupinder Singh","orcid":"0000-0002-9185-7944","position":17,"is_corresponding":false},{"id":237535,"name":"Amol P. Kamboj","orcid":"0000-0003-3611-7326","position":18,"is_corresponding":false},{"id":237536,"name":"Henrik Rasmussen","orcid":"0000-0003-0525-9671","position":19,"is_corresponding":false},{"id":237537,"name":"Marc E. Rothenberg","orcid":"0000-0001-9790-6332","position":20,"is_corresponding":false},{"id":233039,"name":"Ikuo Hirano","orcid":"0000-0001-7688-9377","position":21,"is_corresponding":false},{"id":233047,"name":"Evan S. Dellon","orcid":"0000-0003-1167-1101","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-18T20:36:25.163232Z","pmid":"33085861","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}