{"doi":"10.1371/journal.pone.0306714","title":"Real-world comparative study of drug retention of Janus kinase inhibitors in patients with rheumatoid arthritis","abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background</jats:title>\n<jats:p>Janus kinase (JAK) inhibitors (JAKis) are effective therapeutic agents against rheumatoid arthritis (RA). However, patients having RA with particular risk factors may have a higher incidence of adverse effects (AEs), including major cardiovascular events (MACE) and infections. In this multicenter cohort study, we aimed to clarify the risk factors affecting the drug retention of JAKis in patients with RA.</jats:p>\n</jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods</jats:title>\n<jats:p>We retrospectively evaluated patients with RA who received their first JAKi (tofacitinib, baricitinib, upadacitinib, or filgotinib) at our institute. The clinical outcomes, including AEs, were recorded, particularly MACE and serious infections. The drug retention rates were analyzed using the Kaplan–Meier method, and risk factors affecting drug retention rates were determined using a multivariable Cox regression hazards model.</jats:p>\n</jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results</jats:title>\n<jats:p>Overall 184 patients with RA receiving their first use of baricitinib (57.6%), tofacitinib (23.9%), upadacitinib (12.0%), or filgotinib (6.5%) were included in this study. Fifty-six (30.4%) patients discontinued JAKi treatment owing to ineffectiveness (9.2%) or AEs, including infections (21.2%). The overall drug retention rates were significantly lower in patients treated with pan-JAKi than in those treated with JAK1 inhibitors (<jats:italic>p</jats:italic> = 0.03). In the Cox regression model, the presence of baseline high RA disease activity, use of glucocorticoid and treatments with pan-JAKis were associated with reduced drug retention rates of JAKis (<jats:italic>p</jats:italic> &lt; 0.001, <jats:italic>p</jats:italic> = 0.01 and 0.04, respectively). Pan-JAKi treated patients with high disease activity had significantly lower drug retention rates (<jats:italic>p</jats:italic> &lt; 0.001).</jats:p>\n</jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions</jats:title>\n<jats:p>In a real-world setting, the drug retention rates of JAKis were reduced mainly by treatment discontinuation owing to AEs. Treatment with pan-JAKis and high baseline RA disease activity were identified as predictive factors for the discontinuation of JAKis. Lower drug retention rates were found in patients receiving pan-JAKis with high disease activity than in those without high disease activity.</jats:p>\n</jats:sec>","journal":"PLOS ONE","year":2024,"id":641400,"datarank":0.37273599746820013,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"self_citation_contribution":0.37273599746820013,"citation_network_contribution":0.0,"self_endowment_contribution":0.37273599746820013,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"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":1667671,"name":"Shuhei Yoshida","orcid":"0000-0001-9007-5708","position":1,"is_corresponding":false},{"id":1667672,"name":"Honoka Ebina","orcid":null,"position":2,"is_corresponding":false},{"id":1667673,"name":"Masayuki Miyata","orcid":null,"position":3,"is_corresponding":false},{"id":1667674,"name":"Eiji Suzuki","orcid":null,"position":4,"is_corresponding":false},{"id":1667675,"name":"Takashi Kanno","orcid":null,"position":5,"is_corresponding":false},{"id":1667676,"name":"Yuya Sumichika","orcid":null,"position":6,"is_corresponding":false},{"id":1667677,"name":"Haruki Matsumoto","orcid":null,"position":7,"is_corresponding":false},{"id":1667678,"name":"Jumpei Temmoku","orcid":null,"position":8,"is_corresponding":false},{"id":367182,"name":"Yuya Fujita","orcid":"0000-0003-4163-9356","position":9,"is_corresponding":false},{"id":1667679,"name":"Naoki Matsuoka","orcid":null,"position":10,"is_corresponding":false},{"id":1667680,"name":"Tomoyuki Asano","orcid":null,"position":11,"is_corresponding":false},{"id":1667681,"name":"Shuzo Sato","orcid":null,"position":12,"is_corresponding":false},{"id":1667682,"name":"Kiyoshi Migita","orcid":"0000-0003-1339-5622","position":13,"is_corresponding":false},{"id":1401892,"name":"Kenji Saito","orcid":"0000-0003-2184-7203","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Real-world comparative study of drug retention of Janus kinase inhibitors in patients with rheumatoid arthritis","abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background</jats:title>\n<jats:p>Janus kinase (JAK) inhibitors (JAKis) are effective therapeutic agents against rheumatoid arthritis (RA). However, patients having RA with particular risk factors may have a higher incidence of adverse effects (AEs), including major cardiovascular events (MACE) and infections. In this multicenter cohort study, we aimed to clarify the risk factors affecting the drug retention of JAKis in patients with RA.</jats:p>\n</jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods</jats:title>\n<jats:p>We retrospectively evaluated patients with RA who received their first JAKi (tofacitinib, baricitinib, upadacitinib, or filgotinib) at our institute. The clinical outcomes, including AEs, were recorded, particularly MACE and serious infections. The drug retention rates were analyzed using the Kaplan–Meier method, and risk factors affecting drug retention rates were determined using a multivariable Cox regression hazards model.</jats:p>\n</jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results</jats:title>\n<jats:p>Overall 184 patients with RA receiving their first use of baricitinib (57.6%), tofacitinib (23.9%), upadacitinib (12.0%), or filgotinib (6.5%) were included in this study. Fifty-six (30.4%) patients discontinued JAKi treatment owing to ineffectiveness (9.2%) or AEs, including infections (21.2%). The overall drug retention rates were significantly lower in patients treated with pan-JAKi than in those treated with JAK1 inhibitors (<jats:italic>p</jats:italic> = 0.03). In the Cox regression model, the presence of baseline high RA disease activity, use of glucocorticoid and treatments with pan-JAKis were associated with reduced drug retention rates of JAKis (<jats:italic>p</jats:italic> &lt; 0.001, <jats:italic>p</jats:italic> = 0.01 and 0.04, respectively). Pan-JAKi treated patients with high disease activity had significantly lower drug retention rates (<jats:italic>p</jats:italic> &lt; 0.001).</jats:p>\n</jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions</jats:title>\n<jats:p>In a real-world setting, the drug retention rates of JAKis were reduced mainly by treatment discontinuation owing to AEs. Treatment with pan-JAKis and high baseline RA disease activity were identified as predictive factors for the discontinuation of JAKis. Lower drug retention rates were found in patients receiving pan-JAKis with high disease activity than in those without high disease activity.</jats:p>\n</jats:sec>","is_dataset_classified":null,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"38990897","pmcid":"PMC11239012","openalex_id":"https://openalex.org/W4400527196","authors":[],"funders":[{"funder_name":"Japan Grant-in-Aid for Scientific Research","grant_id":"20K08777","title":null}],"total_grants":1,"fwci":3.605,"citation_percentile":0.93474064,"influential_citations":0,"citation_trend":[{"year":2024,"count":1},{"year":2025,"count":4},{"year":2026,"count":6}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0306714&type=printable","host_type":"journal"},{"url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0306714&type=printable","host_type":"publisher"},{"url":"https://dx.plos.org/10.1371/journal.pone.0306714","host_type":"publisher"},{"url":"https://doi.org/10.1371/journal.pone.0306714","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/38990897","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11239012","host_type":"repository"},{"url":"https://doaj.org/article/f6d64af6494d4cccaaeab5cb597efebf","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11239012/pdf/pone.0306714.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC11239012","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC11239012?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Rheumatoid Arthritis Research and Therapies","Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis","Spondyloarthritis Studies and Treatments"],"mesh_terms":["Janus Kinase Inhibitors","Adult","Aged","Arthritis, Rheumatoid","Azetidines","Female","Heterocyclic Compounds, 3-Ring","Humans","Male","Middle Aged","Piperidines","Purines","Pyrazoles","Pyridines","Pyrimidines","Retrospective Studies","Risk Factors","Sulfonamides","Triazoles","Antirheumatic Agents"],"keywords":["Medicine","Tofacitinib","Rheumatoid arthritis","Internal medicine","Janus kinase inhibitor","Proportional hazards model","Janus kinase","Adverse effect","Mace","Incidence (geometry)","Percutaneous coronary intervention"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-07T17:43:43.349781Z","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":[]}