{"doi":"10.1093/cei/uxae107","title":"Comparative efficacy of leniolisib (CDZ173) versus standard of care on rates of respiratory tract infection and serum immunoglobulin M (IgM) levels among individuals with activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS): an externally controlled study","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>Leniolisib, an oral, targeted phosphoinositide 3-kinase delta (PI3Kδ) inhibitor, was well-tolerated and efficacious versus placebo in treating individuals with activated PI3Kδ syndrome (APDS), an ultra-rare inborn error of immunity (IEI), in a 12-week randomised controlled trial. However, longer-term comparative data versus standard of care are lacking. This externally controlled study compared the long-term effects of leniolisib on annual rate of respiratory tract infections and change in serum immunoglobulin M (IgM) levels versus current standard of care, using data from the leniolisib single-arm open-label extension study 2201E1 (NCT02859727) and the European Society for Immunodeficiencies (ESID) registry. The endpoints were chosen following feasibility assessment considering comparability and availability of data from both sources. Baseline characteristics between groups were balanced through inverse probability of treatment weighting. The leniolisib-treated group included 37 participants, with 62 and 49 participants in the control group for the respiratory tract infections and serum IgM analyses, respectively. Significant reductions in the annual rate of respiratory tract infections (rate ratio: 0.34; 95% confidence interval [CI]: 0.19, 0.59) and serum IgM levels (treatment effect: –1.09 g/L; 95% CI: –1.78, –0.39, P = 0.002) were observed in leniolisib-treated individuals versus standard of care. The results were consistent across all sensitivity analyses, regardless of censoring, baseline infection rate definition, missing data handling, or covariate selection. These novel data provide an extended comparison of leniolisib treatment versus standard of care, highlighting the potential for leniolisib to deliver long-term benefits by restoring immune system function and reducing infection rate, potentially reducing complications and treatment burden.</jats:p>","journal":"Clinical and Experimental Immunology","year":2025,"id":611661,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":614687,"name":"Anita Chandra","orcid":"0000-0002-9061-879X","position":1,"is_corresponding":false},{"id":1034660,"name":"Sven Kracker","orcid":"0000-0003-4543-8236","position":2,"is_corresponding":false},{"id":161578,"name":"Stephan Ehl","orcid":null,"position":3,"is_corresponding":false},{"id":1574377,"name":"Markus G Seidel","orcid":null,"position":4,"is_corresponding":false},{"id":1574378,"name":"Ioana Gulas","orcid":null,"position":5,"is_corresponding":false},{"id":1574379,"name":"Louis Dron","orcid":null,"position":6,"is_corresponding":false},{"id":1574380,"name":"Russanthy Velummailum","orcid":null,"position":7,"is_corresponding":false},{"id":1574381,"name":"Chenthila Nagamuthu","orcid":null,"position":8,"is_corresponding":false},{"id":756928,"name":"Sichen Liu","orcid":"0009-0009-4961-359X","position":9,"is_corresponding":false},{"id":1574382,"name":"Joanne Tutein Nolthenius","orcid":null,"position":10,"is_corresponding":false},{"id":641850,"name":"Maria Elena Maccari","orcid":"0000-0001-6488-7622","position":11,"is_corresponding":false},{"id":1574376,"name":"John Whalen","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Comparative efficacy of leniolisib (CDZ173) versus standard of care on rates of respiratory tract infection and serum immunoglobulin M (IgM) levels among individuals with activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS): an externally controlled study","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>Leniolisib, an oral, targeted phosphoinositide 3-kinase delta (PI3Kδ) inhibitor, was well-tolerated and efficacious versus placebo in treating individuals with activated PI3Kδ syndrome (APDS), an ultra-rare inborn error of immunity (IEI), in a 12-week randomised controlled trial. However, longer-term comparative data versus standard of care are lacking. This externally controlled study compared the long-term effects of leniolisib on annual rate of respiratory tract infections and change in serum immunoglobulin M (IgM) levels versus current standard of care, using data from the leniolisib single-arm open-label extension study 2201E1 (NCT02859727) and the European Society for Immunodeficiencies (ESID) registry. The endpoints were chosen following feasibility assessment considering comparability and availability of data from both sources. Baseline characteristics between groups were balanced through inverse probability of treatment weighting. The leniolisib-treated group included 37 participants, with 62 and 49 participants in the control group for the respiratory tract infections and serum IgM analyses, respectively. Significant reductions in the annual rate of respiratory tract infections (rate ratio: 0.34; 95% confidence interval [CI]: 0.19, 0.59) and serum IgM levels (treatment effect: –1.09 g/L; 95% CI: –1.78, –0.39, P = 0.002) were observed in leniolisib-treated individuals versus standard of care. The results were consistent across all sensitivity analyses, regardless of censoring, baseline infection rate definition, missing data handling, or covariate selection. These novel data provide an extended comparison of leniolisib treatment versus standard of care, highlighting the potential for leniolisib to deliver long-term benefits by restoring immune system function and reducing infection rate, potentially reducing complications and treatment burden.</jats:p>","is_dataset_classified":null,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39673396","pmcid":"PMC11754865","openalex_id":"https://openalex.org/W4405387609","authors":[],"funders":[],"total_grants":0,"fwci":0.6235,"citation_percentile":0.66906916,"influential_citations":0,"citation_trend":[{"year":2025,"count":1},{"year":2026,"count":3}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://academic.oup.com/cei/advance-article-pdf/doi/10.1093/cei/uxae107/60930603/uxae107.pdf","host_type":"journal"},{"url":"https://academic.oup.com/cei/advance-article-pdf/doi/10.1093/cei/uxae107/60930603/uxae107.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/cei/advance-article-pdf/doi/10.1093/cei/uxae107/61226214/uxae107.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/cei/article-pdf/219/1/uxae107/61226214/uxae107.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1093/cei/uxae107","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/39673396","host_type":"repository"},{"url":"https://hal.science/hal-05337101","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11754865","host_type":"repository"},{"url":"https://hdl.handle.net/2108/463124","host_type":"repository"},{"url":"https://freidok.uni-freiburg.de/data/261232","host_type":"repository"},{"url":"https://hal.science/hal-05337101v1/document","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11754865/pdf/uxae107.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC11754865","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC11754865?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Immunodeficiency and Autoimmune Disorders","Chronic Lymphocytic Leukemia Research","Lymphoma Diagnosis and Treatment","Adolescent","Adult","Child","Child, Preschool","Female","Humans","Male","Middle Aged","Young Adult","Class I Phosphatidylinositol 3-Kinases","Immunoglobulin M","Primary Immunodeficiency Diseases","Respiratory Tract Infections","Standard of Care","Treatment Outcome","Observational Studies as Topic","Clinical Trials, Phase II as Topic","Clinical Trials, Phase III as Topic","Activated PI3K-delta Syndrome"],"mesh_terms":["Primary Immunodeficiency Diseases","Adolescent","Adult","Child","Child, Preschool","Female","Humans","Immunoglobulin M","Male","Middle Aged","Respiratory Tract Infections","Treatment Outcome","Clinical Trials, Phase II as Topic","Clinical Trials, Phase III as Topic","Young Adult","Class I Phosphatidylinositol 3-Kinases","Standard of Care","Observational Studies as Topic"],"keywords":["Antibody","Phosphoinositide 3-kinase","Respiratory tract","Medicine","Immunology","Upper respiratory tract infection","Internal medicine","Respiratory system","Biology","PI3K/AKT/mTOR pathway","Signal transduction","Genetics","Infection","Immunoglobulin","Pi3kδ","Esid","Apds","Leniolisib"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Peace, Justice and strong institutions"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-01T21:32:55.609325Z","pmid":null,"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":[]}