One Step Forward: Successful End-of-Treatment Outcomes of Patients With Drug-Resistant Tuberculosis Who Received Concomitant Bedaquiline and Delamanid in Mumbai, India.


Journal

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213

Informations de publication

Date de publication:
02 11 2021
Historique:
received: 08 07 2020
accepted: 14 10 2020
pubmed: 21 10 2020
medline: 11 11 2021
entrez: 20 10 2020
Statut: ppublish

Résumé

The Médecins Sans Frontières Clinic in Mumbai, India, has been providing concomitant bedaquiline (BDQ) and delamanid (DLM) in treatment regimen for patients with drug-resistant tuberculosis (DR-TB) and limited therapeutic options, referred from other healthcare institutions, since 2016. The study documents the end-of-treatment outcomes, culture-conversion rates, and serious adverse events (SAEs) during treatment. This was a retrospective cohort study based on routinely collected program data. In clinic, treatment regimens are designed based on culture drug sensitivity test patterns and previous drug exposures, and are provided for 20-22 months. BDQ and DLM are extended beyond 24 weeks as off-label use. Patients who initiated DR-TB treatment including BDQ and DLM (concomitantly for at least 4 weeks) during February 2016-February 2018 were included. Of the 70 patients included, the median age was 25 (interquartile range [IQR], 22-32) years and 56% were females. All except 1 were fluoroquinolone resistant. The median duration of exposure to BDQ and DLM was 77 (IQR, 43-96) weeks. Thirty-nine episodes of SAEs were reported among 30 (43%) patients, including 5 instances of QTc prolongation, assessed as possibly related to BDQ and/or DLM. The majority (69%) had culture conversion before 24 weeks of treatment. In 61 (87%), use of BDQ and DLM was extended beyond 24 weeks. Successful end-of-treatment outcomes were reported in 49 (70%) patients. The successful treatment outcomes of this cohort show that regimens including concomitant BDQ and DLM for longer than 24 weeks are effective and can be safely administered on an ambulatory basis. National TB programs globally should scale up access to life-saving DR-TB regimens with new drugs.

Sections du résumé

BACKGROUND
The Médecins Sans Frontières Clinic in Mumbai, India, has been providing concomitant bedaquiline (BDQ) and delamanid (DLM) in treatment regimen for patients with drug-resistant tuberculosis (DR-TB) and limited therapeutic options, referred from other healthcare institutions, since 2016. The study documents the end-of-treatment outcomes, culture-conversion rates, and serious adverse events (SAEs) during treatment.
METHODS
This was a retrospective cohort study based on routinely collected program data. In clinic, treatment regimens are designed based on culture drug sensitivity test patterns and previous drug exposures, and are provided for 20-22 months. BDQ and DLM are extended beyond 24 weeks as off-label use. Patients who initiated DR-TB treatment including BDQ and DLM (concomitantly for at least 4 weeks) during February 2016-February 2018 were included.
RESULTS
Of the 70 patients included, the median age was 25 (interquartile range [IQR], 22-32) years and 56% were females. All except 1 were fluoroquinolone resistant. The median duration of exposure to BDQ and DLM was 77 (IQR, 43-96) weeks. Thirty-nine episodes of SAEs were reported among 30 (43%) patients, including 5 instances of QTc prolongation, assessed as possibly related to BDQ and/or DLM. The majority (69%) had culture conversion before 24 weeks of treatment. In 61 (87%), use of BDQ and DLM was extended beyond 24 weeks. Successful end-of-treatment outcomes were reported in 49 (70%) patients.
CONCLUSIONS
The successful treatment outcomes of this cohort show that regimens including concomitant BDQ and DLM for longer than 24 weeks are effective and can be safely administered on an ambulatory basis. National TB programs globally should scale up access to life-saving DR-TB regimens with new drugs.

Identifiants

pubmed: 33079176
pii: 5932278
doi: 10.1093/cid/ciaa1577
doi:

Substances chimiques

Antitubercular Agents 0
Diarylquinolines 0
Nitroimidazoles 0
OPC-67683 0
Oxazoles 0
bedaquiline 78846I289Y

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e3496-e3504

Informations de copyright

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.

Auteurs

Mrinalini Das (M)

Médecins Sans Frontières, Mumbai, India.

Alpa Dalal (A)

Jupiter Hospital, Thane, Maharashtra, India.

Chinmay Laxmeshwar (C)

Médecins Sans Frontières, Mumbai, India.

Shilpa Ravi (S)

Médecins Sans Frontières, Mumbai, India.

Fatima Mamnoon (F)

Médecins Sans Frontières, Mumbai, India.

Augusto C Meneguim (AC)

Médecins Sans Frontières, Mumbai, India.

Roma Paryani (R)

Médecins Sans Frontières, Mumbai, India.

Taanya Mathur (T)

Médecins Sans Frontières, Mumbai, India.

Pramila Singh (P)

Médecins Sans Frontières, Mumbai, India.

Homa Mansoor (H)

Médecins Sans Frontières, Mumbai, India.

Stobdan Kalon (S)

Médecins Sans Frontières, Mumbai, India.

Farah Naz Hossain (FN)

Médecins Sans Frontières, Mumbai, India.

Nathalie Lachenal (N)

Pharmacovigilance Unit, Médecins Sans Frontières, Geneva, Switzerland.

Sylvine Coutisson (S)

Pharmacovigilance Unit, Médecins Sans Frontières, Geneva, Switzerland.

Gabriella Ferlazzo (G)

Southern Africa Medical Unit, Médecins Sans Frontières, Cape Town, South Africa.

Petros Isaakidis (P)

Southern Africa Medical Unit, Médecins Sans Frontières, Cape Town, South Africa.

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