Outcomes of WHO-conforming, longer, all-oral multidrug-resistant TB regimens and analysis implications

Author:

Rich M. L.1,Khan U.2,Zeng C.3,LaHood A.3,Franke M. F.3,Atwood S.4,Bastard M.5,Burhan E.6,Danielyan N.7,Dzhazibekova P. M.8,Gadissa D.9,Ghafoor A.10,Hewison C.11,Islam M. S.12,Kazmi E.13,Khan P. Y.14,Lecca L.15,Maama L. B.16,Melikyan N.17,Naing Y. Y.18,Philippe K.19,Saki N. A.20,Seung K. J.1,Skrahina A.21,Tefera G. B.9,Varaine F.11,Vilbrun S. C.22,Võ L.23,Mitnick C. D.24,Huerga H.5,on behalf of the endTB Observational Study Te

Affiliation:

1. Division of Global Health Equity, Brigham and Women´s Hospital, Boston, MA, Partners In Health, Boston, MA, USA

2. Interactive Research & Development Global, Singapore, Singapore

3. Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA

4. Division of Global Health Equity, Brigham and Women´s Hospital, Boston, MA

5. Epicentre, Paris, France

6. Persahabatan General Hospital, Jakarta, Indonesia

7. Médecins Sans Frontières (MSF), Tbilisi, Georgia

8. National Science Center, Almaty, Republic of Kazakhstan

9. Partners In Health (PIH), Addis Ababa, Ethiopia

10. National Tuberculosis Programme (NTP), Ministry of National Health, Islamabad, Pakistan

11. MSF, Paris, France

12. Interactive Research & Development, Dhaka, Bangladesh

13. Directorate General Health Services, Centers for Disease Control and Prevention, Sindh, Pakistan

14. Partners In Health, Boston, MA, USA, Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK

15. Socios En Salud Sucursal, Lima, Peru

16. PIH, Maseru, Lesotho, NTP, Maseru, Lesotho

17. Epicentre, Paris, France, MSF, Yerevan, Armenia

18. MSF, Yangon, Myanmar

19. Zanmi Lasante, Cange, Haiti

20. World Health Organization, Country Office, Dhaka, Bangladesh

21. MSF, Minsk, Belarus

22. GHESKIO Institute of Infectious Diseases and Reproductive Health, NTP, Port-au-Prince, Haiti

23. Friends for International TB Relief, Ho Chi Minh City, Vietnam

24. Division of Global Health Equity, Brigham and Women´s Hospital, Boston, MA, Partners In Health, Boston, MA, USA, Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA

Abstract

BACKGROUND: Evidence of the effectiveness of the WHO-recommended design of longer individualized regimens for multidrug- or rifampicin-resistant TB (MDR/RR-TB) is limited.OBJECTIVES: To report end-of-treatment outcomes for MDR/RR-TB patients from a 2015–2018 multi-country cohort that received a regimen consistent with current 2022 WHO updated recommendations and describe the complexities of comparing regimens.METHODS: We analyzed a subset of participants from the endTB Observational Study who initiated a longer MDR/RR-TB regimen that was consistent with subsequent 2022 WHO guidance on regimen design for longer treatments. We excluded individuals who received an injectable agent or who received fewer than four likely effective drugs.RESULTS: Of the 759 participants analyzed, 607 (80.0%, 95% CI 77.0–82.7) experienced successful end-of-treatment outcomes. The frequency of success was high across groups, whether stratified on number of Group A drugs or fluoroquinolone resistance, and ranged from 72.1% to 90.0%. Regimens were highly variable regarding composition and the duration of individual drugs.CONCLUSIONS: Longer, all-oral, individualized regimens that were consistent with 2022 WHO guidance on regimen design had high frequencies of treatment success. Heterogeneous regimen compositions and drug durations precluded meaningful comparisons. Future research should examine which combinations of drugs maximize safety/tolerability and effectiveness.

Publisher

International Union Against Tuberculosis and Lung Disease

Subject

Infectious Diseases,Pulmonary and Respiratory Medicine

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