{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:38:42Z","timestamp":1792600722140,"version":"4.5.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-190227"],"award-info":[{"award-number":["PJT-190227"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014131","name":"McGill University Health Centre Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014131","id-type":"DOI","asserted-by":"publisher"}]},{"name":"McGill University Department of Medicine","award":["(#330287"],"award-info":[{"award-number":["(#330287"]}]},{"name":"Canada Graduate Scholarship"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>People receiving immunosuppressive medications are at increased risk of tuberculosis. Tuberculosis preventive treatment (TPT) can reduce risk; however, its safety among these populations is uncertain. We conducted a meta-analysis to evaluate adverse events (AEs) associated with TPT among people receiving or about to initiate immunosuppressive medications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We searched Medline, Cochrane, Health Star, and Embase (1952\u20131 May 2025), for studies reporting AEs during TPT among people receiving or about to initiate immunosuppressive medications. We used random-effects generalized linear mixed models with Hartung\u2013Knapp 95% confidence intervals (CIs) to estimate our primary outcome: pooled proportion of AE-related discontinuation, stratified by TPT regimen.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We included 27 studies (3184 participants). Populations included biologics\/steroids recipients and solid organ\/hematopoietic transplant candidates\/recipients. For the primary outcome (25 studies, 2802 participants), TPT regimens included 6- to 12-month mono-isoniazid regimens (1511 participants), 4-month mono-rifamycin regimens (228 participants), 3-month isoniazid-rifamycin combination regimens (990 participants), and 6- to 9-month fluoroquinolone-based regimens (73 participants). Only mono-isoniazid regimens were provided while receiving immunosuppressive medications. Pooled AE-related discontinuation was 5.3% (95% CI, 3.1%\u20138.9%; I2 = 65.4%) for mono-isoniazid regimens, 4.4% (95% CI, .1%\u201375.4%; I2 = 86.3%) for mono-rifamycin regimens, 2.0% (1.0%\u20134.1%; I2 = 0.0%) for isoniazid-rifamycin combination regimens, and 6.9% (95% CI, 0\u201392.3%; I2 = 65.4%) for fluoroquinolone-based regimens. Proportions were similar when stratified by biologics\/steroids and transplant populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Overall, AE-related TPT discontinuation was similar to that in the broader TPT literature. AE-related discontinuation of TPT was lowest with rifamycin-containing regimens, but these were only provided prior to initiating immunosuppressive medications. Data on the safety of non-isoniazid regimens among people receiving immunosuppressive medications are needed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciag584","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T19:18:16Z","timestamp":1789672696000},"source":"Crossref","is-referenced-by-count":0,"title":["Safety of Tuberculosis Preventive Treatment Among People Receiving or About to Initiate Immunosuppressive Medications: A Systematic Review and Meta-analysis"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4237-9246","authenticated-orcid":false,"given":"Anabel","family":"Selemon","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Biostatistics, and Occupational Health, McGill University , Montreal, Quebec ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Lima","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Institute for the Study of International Development, McGill University , Montreal, Quebec ,","place":["Canada"]},{"name":"Department of Political Science, McGill University , Montreal, Quebec ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamila","family":"Romanowski","sequence":"additional","affiliation":[{"name":"British Columbia Centre for Disease Control Provincial TB Services, , Vancouver, British Columbia ,","place":["Canada"]},{"name":"Division of Respiratory Medicine, University of British Columbia , Vancouver, British Columbia ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Melnychuk","sequence":"additional","affiliation":[{"name":"Department of Medicine, McGill University , Montreal, Quebec ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1601-4514","authenticated-orcid":false,"given":"Dick","family":"Menzies","sequence":"additional","affiliation":[{"name":"Department of Medicine, McGill University , Montreal, Quebec ,","place":["Canada"]},{"name":"McGill International TB Centre, McGill University , Montreal, Quebec ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria J","family":"Cook","sequence":"additional","affiliation":[{"name":"British Columbia Centre for Disease Control Provincial TB Services, , Vancouver, British Columbia ,","place":["Canada"]},{"name":"Division of Respiratory Medicine, University of British Columbia , Vancouver, British Columbia ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3051-0701","authenticated-orcid":false,"given":"Dina","family":"Fisher","sequence":"additional","affiliation":[{"name":"Department of Medicine and Community Health Sciences, University of Calgary , Calgary, Alberta ,","place":["Canada"]},{"name":"Calgary TB Services , Calgary, Alberta ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4449-4447","authenticated-orcid":false,"given":"Rachel K","family":"Lim","sequence":"additional","affiliation":[{"name":"Calgary TB Services , Calgary, Alberta ,","place":["Canada"]},{"name":"Department of Medicine, University of Calgary , Calgary, Alberta ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3855-6368","authenticated-orcid":false,"given":"Sarah K","family":"Brode","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Toronto , Toronto, Ontario ,","place":["Canada"]},{"name":"University Health Network , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8879-4989","authenticated-orcid":false,"given":"James C","family":"Johnston","sequence":"additional","affiliation":[{"name":"British Columbia Centre for Disease Control Provincial TB Services, , Vancouver, British Columbia ,","place":["Canada"]},{"name":"Division of Respiratory Medicine, University of British Columbia , Vancouver, British Columbia ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayara L","family":"Bastos","sequence":"additional","affiliation":[{"name":"McGill International TB Centre, McGill University , Montreal, Quebec ,","place":["Canada"]},{"name":"Division of Infectious Diseases, Department of Medicine and Department of Medical Microbiology and Infectious Diseases, University of Manitoba , Winnipeg, Manitoba ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2341-2166","authenticated-orcid":false,"given":"Jonathon R","family":"Campbell","sequence":"additional","affiliation":[{"name":"Department of Medicine, McGill University , Montreal, Quebec ,","place":["Canada"]},{"name":"McGill International TB Centre, McGill University , Montreal, Quebec ,","place":["Canada"]},{"name":"Respiratory Epidemiology and Clinical Research Unit, Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre , Montreal, Quebec ,","place":["Canada"]},{"name":"Department of Global and Public Health, McGill University , Montreal, Quebec ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"2026102111431554600_ciag584-B1","author":"World Health Organization"},{"key":"2026102111431554600_ciag584-B2","author":"Public Health Agency of Canada"},{"key":"2026102111431554600_ciag584-B3","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1093\/jac\/dkr159","article-title":"Hepatic safety of antibiotics used in primary care","volume":"66","author":"Andrade","year":"2011","journal-title":"J Antimicrob Chemother"},{"key":"2026102111431554600_ciag584-B4","doi-asserted-by":"crossref","first-page":"102266.","DOI":"10.1016\/j.coi.2022.102266","article-title":"The increasing prevalence of autoimmunity and autoimmune diseases: an urgent call to action for improved understanding, diagnosis, treatment and prevention","volume":"80","author":"Miller","year":"2023","journal-title":"Curr Opin Immunol"},{"key":"2026102111431554600_ciag584-B5","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1182\/hematology.2021000258","article-title":"Increasing access to allogeneic hematopoietic cell transplant: an international perspective","volume":"2021","author":"Rocha","year":"2021","journal-title":"Hematology"},{"key":"2026102111431554600_ciag584-B6","doi-asserted-by":"crossref","first-page":"S443","DOI":"10.1016\/j.ajt.2023.02.010","article-title":"OPTN\/SRTR 2021 annual data report: deceased organ donation","volume":"23","author":"Israni","year":"2023","journal-title":"Am J Transplant"},{"key":"2026102111431554600_ciag584-B7","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1001\/jama.2023.28019","article-title":"Prevalence of immunosuppression among US adults","volume":"331","author":"Martinson","year":"2024","journal-title":"JAMA"},{"key":"2026102111431554600_ciag584-B8","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1093\/cid\/ciae561","article-title":"Predicting risk of tuberculosis (TB) disease in people who migrate to a low-TB incidence country: development and validation of a multivariable, dynamic risk-prediction model using health administrative data","volume":"80","author":"Puyat","year":"2025","journal-title":"Clin Infect Dis"},{"key":"2026102111431554600_ciag584-B9","doi-asserted-by":"crossref","first-page":"e012567","DOI":"10.1136\/bmjopen-2016-012567","article-title":"Risk of tuberculosis in patients treated with TNF-\u03b1 antagonists: a systematic review and meta-analysis of randomised controlled trials","volume":"7","author":"Zhang","year":"2017","journal-title":"BMJ Open"},{"key":"2026102111431554600_ciag584-B10","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1086\/599035","article-title":"Tuberculosis after solid-organ transplant: incidence, risk factors, and clinical characteristics in the RESITRA (Spanish Network of Infection in Transplantation) cohort","volume":"48","author":"Torre-Cisneros","year":"2009","journal-title":"Clin Infect Dis"},{"key":"2026102111431554600_ciag584-B11","doi-asserted-by":"crossref","first-page":"730","DOI":"10.4046\/trd.2024.0197","article-title":"Incidence, risk factors, and mortality associated with tuberculosis in solid organ transplant recipients in Taiwan","volume":"88","author":"Chuang","year":"2025","journal-title":"Tuberc Respir Dis"},{"key":"2026102111431554600_ciag584-B12","doi-asserted-by":"crossref","first-page":"ofab641","DOI":"10.1093\/ofid\/ofab641","article-title":"Association of tumor necrosis factor \u03b1 inhibitor use with diagnostic features and mortality of tuberculosis in the United States, 2010\u20132017","volume":"9","author":"Katrak","year":"2022","journal-title":"Open Forum Infect Dis"},{"key":"2026102111431554600_ciag584-B13","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1093\/cid\/ciad246","article-title":"A systematic review and meta-analysis of tuberculous preventative therapy adverse events","volume":"77","author":"Melnychuk","year":"2023","journal-title":"Clin Infect Dis"},{"key":"2026102111431554600_ciag584-B14","first-page":"498","article-title":"Thinking in three dimensions: a web-based algorithm to aid the interpretation of tuberculin skin test results","volume":"12","author":"Menzies","year":"2008","journal-title":"Int J Tuberc Lung Dis"},{"key":"2026102111431554600_ciag584-B15","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1038\/s41591-020-1076-0","article-title":"Discovery and validation of a personalized risk predictor for incident tuberculosis in low transmission settings","volume":"26","author":"Gupta","year":"2020","journal-title":"Nat Med"},{"key":"2026102111431554600_ciag584-B16","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"2026102111431554600_ciag584-B17","author":"Veritas Health Innovation"},{"key":"2026102111431554600_ciag584-B18","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1002\/jrsm.1411","article-title":"Risk-of-bias VISualization (robvis): an R package and Shiny web app for visualizing risk-of-bias assessments","volume":"12","author":"McGuinness","year":"2021","journal-title":"Res Synth Methods"},{"key":"2026102111431554600_ciag584-B19","first-page":"153","article-title":"How to perform a meta-analysis with R: a practical tutorial","volume":"22","author":"Balduzzi","year":"2019","journal-title":"BMJ Ment Health"},{"key":"2026102111431554600_ciag584-B20","doi-asserted-by":"crossref","first-page":"3875","DOI":"10.1002\/sim.1009","article-title":"A refined method for the meta-analysis of controlled clinical trials with binary outcome","volume":"20","author":"Hartung","year":"2001","journal-title":"Stat Med"},{"key":"2026102111431554600_ciag584-B21","doi-asserted-by":"crossref","DOI":"10.1002\/9781119536604","volume-title":"Cochrane handbook for systematic reviews of interventions","author":"Higgins","year":"2019"},{"key":"2026102111431554600_ciag584-B22","doi-asserted-by":"crossref","first-page":"2304","DOI":"10.1056\/NEJMoa2314325","article-title":"Levofloxacin for the prevention of multidrug-resistant tuberculosis in Vietnam","volume":"391","author":"Fox","year":"2024","journal-title":"N Engl J Med"},{"key":"2026102111431554600_ciag584-B23","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1157\/13102264","article-title":"Short-course isoniazid and rifampin compared with isoniazid for latent tuberculosis infection: a randomized clinical trial [in Spanish]","volume":"25","author":"Paloma Geijo","year":"2007","journal-title":"Enferm Infecc Microbiol Clin"},{"key":"2026102111431554600_ciag584-B24","doi-asserted-by":"crossref","first-page":"2155","DOI":"10.1056\/NEJMoa1104875","article-title":"Three months of rifapentine and isoniazid for latent tuberculosis infection","volume":"365","author":"Sterling","year":"2011","journal-title":"N Engl J Med"},{"key":"2026102111431554600_ciag584-B25","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/S1473-3099(19)30575-4","article-title":"Adverse events in adults with latent tuberculosis infection receiving daily rifampicin or isoniazid: post-hoc safety analysis of two randomised controlled trials","volume":"20","author":"Campbell","year":"2020","journal-title":"Lancet Infect Dis"},{"key":"2026102111431554600_ciag584-B26","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/S2213-2600(23)00096-6","article-title":"Completion, safety, and efficacy of tuberculosis preventive treatment regimens containing rifampicin or rifapentine: an individual patient data network meta-analysis","volume":"11","author":"Winters","year":"2023","journal-title":"Lancet Respir Med"},{"key":"2026102111431554600_ciag584-B27","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1056\/NEJMoa1714283","article-title":"Four months of rifampin or nine months of isoniazid for latent tuberculosis in adults","volume":"379","author":"Menzies","year":"2018","journal-title":"N Engl J Med"},{"key":"2026102111431554600_ciag584-B28","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1007\/s10067-021-05969-0","article-title":"Safety of latent tuberculosis infection treatment in older patients with immune-mediated inflammatory diseases","volume":"41","author":"Chung","year":"2022","journal-title":"Clin Rheumatol"},{"key":"2026102111431554600_ciag584-B29","doi-asserted-by":"crossref","first-page":"107849","DOI":"10.1016\/j.ijid.2025.107849","article-title":"Update on multidrug-resistant tuberculosis preventive therapy toward the global tuberculosis elimination","volume":"155","author":"Matteelli","year":"2025","journal-title":"Int J Infect Dis"},{"key":"2026102111431554600_ciag584-B30","doi-asserted-by":"crossref","first-page":"819","DOI":"10.2165\/00003088-200342090-00003","article-title":"Pharmacokinetic interactions with rifampicin","volume":"42","author":"Niemi","year":"2003","journal-title":"Clin Pharmacokinet"},{"key":"2026102111431554600_ciag584-B31","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/j.jaad.2024.11.071","article-title":"North American clinical practice guidelines for the medical management of hidradenitis suppurativa in special patient populations","volume":"92","author":"Alhusayen","year":"2025","journal-title":"J Am Acad Dermatol"},{"key":"2026102111431554600_ciag584-B32","doi-asserted-by":"crossref","first-page":"e1004438","DOI":"10.1371\/journal.pmed.1004438","article-title":"Research on the treatment of rifampin-susceptible tuberculosis\u2014time for a new approach","volume":"21","author":"Burman","year":"2024","journal-title":"PLoS Med"},{"key":"2026102111431554600_ciag584-B33","doi-asserted-by":"crossref","first-page":"m549","DOI":"10.1136\/bmj.m549","article-title":"Absolute risk of tuberculosis among untreated populations with a positive tuberculin skin test or interferon-gamma release assay result: systematic review and meta-analysis","volume":"368","author":"Campbell","year":"2020","journal-title":"BMJ"},{"key":"2026102111431554600_ciag584-B34","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1016\/S1473-3099(20)30276-0","article-title":"Interferon-\u03b3 release assays or tuberculin skin test for detection and management of latent tuberculosis infection: a systematic review and meta-analysis","volume":"20","author":"Zhou","year":"2020","journal-title":"Lancet Infect Dis"},{"key":"2026102111431554600_ciag584-B35","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/S0140-6736(20)30166-5","article-title":"The risk of tuberculosis in children after close exposure: a systematic review and individual-participant meta-analysis","volume":"395","author":"Martinez","year":"2020","journal-title":"Lancet"},{"key":"2026102111431554600_ciag584-B36","author":"National Cancer Institute"},{"key":"2026102111431554600_ciag584-B37","author":"National Institute of Allergy and Infectious Diseases"},{"key":"2026102111431554600_ciag584-B38","doi-asserted-by":"crossref","first-page":"741","DOI":"10.2147\/TCRM.S246328","article-title":"Comparison of adverse event profiles of tumor necrosis factor-alfa inhibitors: analysis of a spontaneous reporting database","volume":"16","author":"Wakabayashi","year":"2020","journal-title":"Ther Clin Risk Manag"},{"key":"2026102111431554600_ciag584-B39","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1007\/s40259-023-00603-8","article-title":"Assessment of reported adverse events after interchanging between TNF-\u03b1 inhibitor biosimilars in the WHO pharmacovigilance database","volume":"37","author":"Pauline","year":"2023","journal-title":"BioDrugs"}],"container-title":["Clinical Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cid\/advance-article-pdf\/doi\/10.1093\/cid\/ciag584\/71279462\/ciag584.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/advance-article-pdf\/doi\/10.1093\/cid\/ciag584\/71279462\/ciag584.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:43:28Z","timestamp":1792597408000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cid\/advance-article\/doi\/10.1093\/cid\/ciag584\/8824042"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,21]]},"references-count":39,"URL":"https:\/\/doi.org\/10.1093\/cid\/ciag584","relation":{},"ISSN":["1058-4838","1537-6591"],"issn-type":[{"value":"1058-4838","type":"print"},{"value":"1537-6591","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,21]]},"article-number":"ciag584"}}