Mohammad Javad Nasiri1, Moein Zangiabadian2, Erfan Arabpour3, Sirus Amini4, Farima Khalili5, Rosella Centis6, Lia D'Ambrosio7, Justin T Denholm8, H Simon Schaaf9, Martin van den Boom10, Xhevat Kurhasani11, Margareth Pretti Dalcolmo12, Seif Al-Abri13, Jeremiah Chakaya14, Jan-Willem Alffenaar15, Onno Akkerman16, Denise Rossato Silva17, Marcela Muňoz-Torrico18, Barbara Seaworth19, Emanuele Pontali20, Laura Saderi21, Simon Tiberi22, Alimuddin Zumla23, Giovanni Battista Migliori24, Giovanni Sotgiu25. 1. Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: mj.nasiri@hotmail.com. 2. Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: zangiabadian1998@gmail.com. 3. Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: erfanarabpour1999@gmail.com. 4. Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: sirusamini@gmail.com. 5. Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: farimakhalili@yahoo.com. 6. Servizio di Epidemiologia Clinica delle Malattie Respiratorie, Istituti Clinici Scientifici Maugeri IRCCS, Tradate, Italy. Electronic address: rosella.centis@icsmaugeri.it. 7. Public Health Consulting Group, Lugano, Switzerland. Electronic address: liadambrosio59@gmail.com. 8. Victorian Tuberculosis Program, Melbourne Health, Victoria, Australia; Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia. Electronic address: justin.denholm@mh.org.au. 9. Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. Electronic address: hss@sun.ac.za. 10. World Health Organization Regional Office for the Eastern Mediterranean Region, Cairo, Egypt. Electronic address: vandenboomm@who.int. 11. UBT Higher Education Institution, Prishtina, Kosovo. Electronic address: xhevat.kurhasani@gmail.com. 12. Reference Center Hélio Fraga, Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil. Electronic address: margarethdalcolmo@gmail.com. 13. Directorate General for Disease Surveillance and Control, Ministry of Health, Muscat, Oman. Electronic address: salabri@gmail.com. 14. Department of Medicine, dermatology and therapeutics, Kenyatta University, Nairobi, Kenya; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom. Electronic address: chakaya.jm@gmail.com. 15. Sydney Institute of Infectious Diseases, University of Sydney, Sydney, NSW, Australia; School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; Westmead Hospital, Sydney, NSW, Australia. Electronic address: johannes.alffenaar@sydney.edu.au. 16. University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases and Tuberculosis, Groningen, the Netherlands; University of Groningen, University Medical Center Groningen, Tuberculosis center Beatrixoord, Haren, the Netherlands. Electronic address: o.w.akkerman@umcg.nl. 17. Faculdade de Medicina, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. Electronic address: denise.rossato@terra.com.br. 18. Tuberculosis clinic, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, Mexico. Electronic address: dra_munoz@hotmail.com. 19. Department of Medicine University of Texas Health Science Center, Tyler, Texas. Electronic address: Barbara.Seaworth@dshs.texas.gov. 20. Department of Infectious Diseases, Galliera Hospital, Genoa, Italy. Electronic address: pontals@yahoo.com. 21. Unità di Epidemiologia Clinica e Statistica Medica, Dipartimento di Scienze Mediche Chirurgiche e Sperimentali, Università degli Studi di Sassari, Sassari, Italia. Electronic address: lsaderi@uniss.it. 22. Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom. Electronic address: s.tiberi@qmul.ac.uk. 23. Division of Infection and Immunity, Centre for Clinical Microbiology, University College London, London, United Kingdom; National Institute for Health Research Biomedical Research Centre, UCL Hospitals NHS Foundation Trust, London, United Kingdom. Electronic address: a.zumla@ucl.ac.uk. 24. Servizio di Epidemiologia Clinica delle Malattie Respiratorie, Istituti Clinici Scientifici Maugeri IRCCS, Tradate, Italy. Electronic address: giovannibattista.migliori@icsmaugeri.it. 25. Unità di Epidemiologia Clinica e Statistica Medica, Dipartimento di Scienze Mediche Chirurgiche e Sperimentali, Università degli Studi di Sassari, Sassari, Italia. Electronic address: gsotgiu@uniss.it.
Abstract
INTRODUCTION: Multidrug-resistant tuberculosis (MDR-TB) is a life-threatening condition needing long poly-chemotherapy regimens. As no systematic reviews/meta-analysis is available to comprehensively evaluate the role of delamanid (DLM), we evaluated its effectiveness and safety. METHODS: We reviewed the relevant scientific literature published up to January 20, 2022. The pooled success treatment rate with 95% confidence intervals (CI) was assessed using a random-effect model. We assessed studies for quality and bias, and considered P<0.05 to be statistically significant. RESULTS: After reviewing 626 records, we identified 25 studies that met the inclusion criteria, 22 observational and 3 experimental, with 1276 and 411 patients, respectively. In observational studies the overall pooled treatment success rate of DLM-containing regimens was 80.9% (95% CI 72.6-87.2) with no evidence of publication bias (Begg's test; P >0.05). The overall pooled treatment success rate in DLM and bedaquiline-containing regimens was 75.2% (95% CI 68.1-81.1) with no evidence of publication bias (Begg's test; P >0.05). In experimental studies the pooled treatment success rate of DLM-containing regimens was 72.5 (95% CI 44.2-89.8, P <0.001, I2: 95.1%) with no evidence of publication bias (Begg's test; P >0.05). CONCLUSIONS: In MDR-TB patients receiving DLM, culture conversion and treatment success rates were high despite extensive resistance with limited adverse events.
INTRODUCTION: Multidrug-resistant tuberculosis (MDR-TB) is a life-threatening condition needing long poly-chemotherapy regimens. As no systematic reviews/meta-analysis is available to comprehensively evaluate the role of delamanid (DLM), we evaluated its effectiveness and safety. METHODS: We reviewed the relevant scientific literature published up to January 20, 2022. The pooled success treatment rate with 95% confidence intervals (CI) was assessed using a random-effect model. We assessed studies for quality and bias, and considered P<0.05 to be statistically significant. RESULTS: After reviewing 626 records, we identified 25 studies that met the inclusion criteria, 22 observational and 3 experimental, with 1276 and 411 patients, respectively. In observational studies the overall pooled treatment success rate of DLM-containing regimens was 80.9% (95% CI 72.6-87.2) with no evidence of publication bias (Begg's test; P >0.05). The overall pooled treatment success rate in DLM and bedaquiline-containing regimens was 75.2% (95% CI 68.1-81.1) with no evidence of publication bias (Begg's test; P >0.05). In experimental studies the pooled treatment success rate of DLM-containing regimens was 72.5 (95% CI 44.2-89.8, P <0.001, I2: 95.1%) with no evidence of publication bias (Begg's test; P >0.05). CONCLUSIONS: In MDR-TB patients receiving DLM, culture conversion and treatment success rates were high despite extensive resistance with limited adverse events.
Authors: J W C Alffenaar; S L Stocker; L Davies Forsman; A Garcia-Prats; S K Heysell; R E Aarnoutse; O W Akkerman; A Aleksa; R van Altena; W Arrazola de Oñata; P K Bhavani; N Van't Boveneind-Vrubleuskaya; A C C Carvalho; R Centis; J M Chakaya; D M Cirillo; J G Cho; L D Ambrosio; M P Dalcolmo; P Denti; K Dheda; G J Fox; A C Hesseling; H Y Kim; C U Köser; B J Marais; I Margineanu; A G Märtson; M Munoz Torrico; H M Nataprawira; C W M Ong; R Otto-Knapp; C A Peloquin; D R Silva; R Ruslami; P Santoso; R M Savic; R Singla; E M Svensson; A Skrahina; D van Soolingen; S Srivastava; M Tadolini; S Tiberi; T A Thomas; Z F Udwadia; D H Vu; W Zhang; S G Mpagama; T Schön; G B Migliori Journal: Int J Tuberc Lung Dis Date: 2022-06-01 Impact factor: 3.427