Strengthened capacity of India´s bedaquiline Conditional Access Programme for introducing new drugs and regimens.pdf

INT J TUBERC LUNG DIS 24(10):1067–1072
Q 2020 The Union
http://dx.doi.org/10.5588/ijtld.20.0136
FOCUS ON BDQ
Strengthened capacity of India’s bedaquiline Conditional Access
Programme for introducing new drugs and regimens
K. S. Sachdeva,1 N. Arora,2 R. Solanki,3 R. Singla,4 R. Sarin,4 A. Bhatnagar,5 A. Khanna,6
A. Atahavale,7 R. Shridhar,8 S. R. Barua,9 M. Parmar,10 S. I. Farooq,2 R. Ramachandran,10
U. Alavadi,11 R. Swamickan,11 J. Tonsing,2 Y. Patel,1 N. Singla4
1
Central TB Division, Ministry of Health and Family Welfare, Government of India, New Delhi, 2
International
Union Against Tuberculosis and Lung Disease South East Asia, New Delhi, 3
BJ Medical College and Hospital,
Ahmedabad, 4
National Institute for TB and Respiratory Disease, New Delhi, 5
Rajan Babu Institute for Pulmonary
Medicine and Tuberculosis, New Delhi, 6
Government of National Capital Territory of Delhi, New Delhi, 7
King
Edward Memorial College & Group of TB Hospital, Mumbai, 8
Government Hospital of Thoracic Medicine, Chennai,
9
Guwahati Medical College, Guwahati, 10
World Health Organisation, India Country Office, New Delhi, 11
United
States Agency for International Development India, New Delhi, India
S U M M A R Y
B A C K G R O U N D : Addressing TB in India is critical to
meeting global targets. With the scale-up of diagnostic
networks and the availability of new TB drugs, India
had the opportunity to improve the detection and
treatment outcomes in drug-resistant TB (DR-TB).
O B J E C T I V E : To document how the introduction of new
drugs and regimens is helping India improve the care of
DR-TB patients.
D E S I G N : In 2016, India’s National TB Programme
(NTP) introduced bedaquiline (BDQ) under a Condi-
tional Access Programme (BDQ-CAP) at six sites after
providing extensive training and strengthening labora-
tory testing, pre-treatment evaluation, active drug safety
monitoring and management (aDSM) and follow-up
systems.
R E S U LT S : An interim analysis reflected earlier and
better culture conversion rates: 83% of the 620 patients
converted within a median time of 60 days. However,
248 serious adverse events were reported, including 73
deaths (12%) and 100 cardiotoxicity events (16.3%).
Encouraged by the evidence of safety and efficacy of
BDQ, the NTP took steps to systematically expand its
access to cover the entire population by 2018.
C O N C L U S I O N : The cautious yet focused approach used
to introduce BDQ under BDQ-CAP paved the way for
the rapid introduction of delamanid, as well as the
shorter treatment regimen and the all-oral regimen for
DR-TB.
K E Y W O R D S : tuberculosis; BDQ CAP; delamanid;
aDSM; DRTB
ADDRESSING THE PROBLEM of TB in India,
which contributes to more than a quarter of the
estimated global TB burden, has remained critical to
accomplishing global TB control targets. New sur-
veillance and survey data from India confirmed that
the TB epidemic was much larger than previously
estimated. While the National TB Programme (NTP)
has been making progress in finding one million
‘‘missing’’ TB patients, progress in detecting multi-
drug-resistant TB (MDR-TB) cases has been compar-
atively slow. In 2016, while only 37% of the
estimated 2 790 000 incident TB cases were undetect-
ed, 78% of the estimated 147 000 incident MDR-TB
cases were missing. The treatment success rate in
MDR-TB cases has also been less than 50% over the
years.1 The diagnosis and treatment of MDR-TB
require more tests, drugs, expertise and resources.
The drugs available to treat MDR-TB are less
effective and more toxic, leading to poorer treatment
outcomes with more patients lost to follow-up due to
drug intolerance and death.2–4 There was thus an
urgent need for the introduction of safer, newer drugs
and regimens in India.5
Bedaquiline (BDQ), an anti-TB drug developed
after a gap of about 40 years, was approved by the US
Food and Drug Administration in December 2012
based on Phase IIb data. The WHO subsequently
issued interim policy guidance on BDQ use in June
2013.6 Given the limited evidence on BDQ at the
time, the WHO advised a phased approach to BDQ
implementation, subject to the following five condi-
tions: treatment is administered under closely mon-
itored conditions; patient inclusion criteria are
adhered to; informed consent is obtained from
patients; principles for designing a WHO-recom-
mended MDR-TB regimen are followed; and phar-
Correspondence to: Neerja Arora, The Union South East Asia, New Delhi, C-6, Qutub Institutional Area, New Delhi
110016, India. e-mail: Narora@theunion.org
Article submitted 9 March 2020. Final version accepted 15 May 2020.

macovigilance, proper management of adverse drug
reactions and the prevention of drug-drug interac-
tions are observed.6–8
In India, BDQ first became available through a
compassionate use mechanism. It is to be noted that
at Hinduja Hospital in Mumbai, 70% of a cohort of
20 heavily pre-treated patients who received BDQ
under the compassionate use programme were
culture-negative at 6 months of treatment, and at
least 55% were cured.9. With the scale-up of TB
culture and drug susceptibility testing (DST) labora-
tories, which included about 1200 GeneXpert sys-
tems (Cepheid, Sunnyvale, CA, USA) across the
country, and the availability of new TB drugs (BDQ
and delamanid [DLM]), an opportunity to improve
detection and treatment outcomes in MDR-TB
patients could be envisaged. India’s NTP was able
to access 10 000 patient courses of BDQ through the
United States Agency for International Development
(USAID) and the Bedaquiline Donation Programme
of Janssen Therapeutics (Beerse, Belgium).10
This paper documents how the introduction of new
drugs and regimens is helping India improve the care
of DR-TB patients.
METHOD
From intent to implementation
The Government of India constituted a National
Expert Committee on Regulation of Newer anti-TB
drugs to review the WHO interim recommendation
for the introduction of BDQ. Following the commit-
tee’s approval, the Apex Committee of the Ministry of
Health and Family Welfare approved the use of BDQ
as a part of the combination chemotherapy for
pulmonary MDR-TB in adults aged 18 years. Given
the strong demand generated by the limited treatment
options available for MDR-TB, the Drug Controller
General of India approved a recommended waiver of
clinical trials and permitted the import of BDQ for
conditional use in MDR-TB patients under the
NTP.11
In addition to other potential side effects, there
were concerns about the increased cardiotoxicity
associated with the use of BDQ.12–16 Accordingly, the
NTP took a cautious and systematic approach, first
reviewing the safety and efficacy profile of BDQ in a
defined number of MDR-TB patients at selected DR-
TB treatment centres under a Bedaquiline Condition-
al Access Programme (BDQ-CAP). Six sites were
identified based on geographical representation from
different regions of the country and the institution’s
capacity for active drug safety monitoring and
management (aDSM) of potential adverse events
(AEs).11
National experts with technical input from WHO
Geneva and other leading global institutions issued
comprehensive guidelines for the use of BDQ under
conditional access in 2016. Potential risks and
benefits were assessed and explicit criteria for
inclusion and exclusion were defined.11
Preparations for the roll-out of BDQ under NTP’s
Programmatic Management of Drug-Resistant TB
A national Training of Trainers course on the
implementation of BDQ-CAP was organised in
January 2016. This was followed by rigorous training
and capacity building for the staff at the six sites
selected on the use of BDQ in combination with the
optimised background regimen (OBR) designed and
tailored for individuals based on DST results and
previous medication history. Each site was linked to a
well-equipped TB culture and DST laboratory. The
pre-treatment evaluation included a range of labora-
tory tests and comprehensive clinical assessments to
rule out conditions that could potentially put patients
at an increased risk of AEs. In collaboration with the
Pharmacovigilance Programme of India, the NTP
developed a comprehensive aDSM system to monitor
adverse drug reactions in line with WHO’s recom-
mendations for an aDSM implementation frame-
work.8,17 India opted for intensive cohort event
monitoring for BDQ-CAP, recommended in the
2013 WHO Interim guidance on the use of BDQ.6
A Drug Safety Monitoring Committee was estab-
lished at the national level, and a Causality Assess-
ment Committee was established at each BDQ-CAP
site to review AEs, grade those using Division of AIDS
criteria, and assess their relatedness and causality to
individual drugs in the treatment regimen.
BDQ was introduced at six sites in March 2016
and the first patient was initiated in Guwahati on 6
June 2016. Patients with extensively drug-resistant
tuberculosis (XDR-TB) were initially considered
eligible for inclusion in BDQ-CAP. The NTP regularly
reviewed the progress, and an early review showed
very slow and highly selective enrolment of eligible
patients due to the strict inclusion criteria, so that
only eight patients were initiated in the first 2 months
at the six sites. In August 2016, the NTP after
reviewing the factors contributing to slow enrolment
decided to include MDR-TB patients with resistance
to fluoroquinolones or second-line injectables or
mixed pattern of drug resistance under BDQ-CAP.
In October 2016, an expert committee reviewed the
status and recommended the expansion of access to
BDQ-CAP to other geographical sites. In January
2017, the NTP advised all states to prepare for BDQ
roll-out and provided detailed prerequisites, check-
lists and action plans to help facilitate the implemen-
tation (Figure 1).
Information in this study was obtained from
programme guidelines and referenced documents.
As the study did not include any patient-specific data,
ethical approval was not required.
1068 The International Journal of Tuberculosis and Lung Disease

RESULTS
In-country evidence on the safety and efficacy of BDQ-
containing treatment regimens
A study on the effectiveness and safety of BDQ under
the CAP in India provided interim analysis of a cohort
of MDR-TB cases.18 Of the 620 patients with MDR-
TB included, 513 (83%) patients had sputum culture
conversion within 6 months, with the median time to
culture conversion of 60 days. A total of 248 serious
AEs were reported, including 73 deaths (12%).
Approximately 100 patients (16.3%) experienced a
60 ms increase in QTc intervals during the
treatment. The findings corroborate those presented
by Borisov et al and confirm the safety and
effectiveness of BDQ when used at the programme
level.19
Among the 290 patients initiated under BDQ-CAP
at the National Institute of Tuberculosis and Respi-
ratory Diseases, New Delhi, India, respectively 93%
and 98% patients had culture conversion within 3
and 6 months. The site reported 201 episodes of AEs
in all, of which 38.8% were severe.20 In the cohort of
127 patients at the Ahmedabad BDQ-CAP site, the
median time for culture conversion was 41 days; the
majority of the 124 (86.3%) AEs were non-serious
and 102 (80.3%) patients had successful treatment
outcome.21
Nationwide scale-up of access to BDQ, 2018–2019
The interim analysis of BDQ-CAP safety and
effectiveness data reflected earlier and better culture
conversion rates and less than anticipated cardiotox-
icity. The Drug Safety Monitoring Committee there-
fore recommended the scale up of access to BDQ, and
the NTP expanded access across the country in 2018.
The new national PMDT guidelines22 allowed BDQ
to be initiated without mandatory hospitalisation.
The follow-up monitoring schedule was modified for
the feasibility of implementation under field condi-
tions. The introduction of line-probe assays for
second-line drugs (SL-LPA) in 2017 reduced the time
required to detect resistance to fluoroquinolone and
second-line injectables and identify patients eligible
for BDQ-containing regimens.
However, similar to the experience of BDQ-CAP,
uptake during the scale-up phase was slow. In
response the NTP, in collaboration with the Interna-
tional Union Against Tuberculosis and Lung Disease
(The Union) under the USAID-funded Challenge TB
Project, organised three experience-sharing work-
shops covering all regions of the country. During the
workshops, experts from the initial six BDQ-CAP
sites interacted with treating physicians and shared
their experience in using BDQ, emphasising safety,
effectiveness and the management of AEs. Several
virtual capacity building sessions were also conducted
through the ECHO (Extension for Community
Healthcare Outcomes) platform to discuss case
scenarios, and build the confidence of clinicians and
programme managers using BDQ (Figures 2 and 3).
DISCUSSION
BDQ is an independent predictor of survival and
favourable treatment outcomes, and its use in
conjunction with an OBR results in increased
disability-adjusted life years averted and reduced
healthcare costs.23 Use of BDQ-containing regimens
in patients with MDR-TB in South Africa led to a
41% increase in treatment success and decreased
mortality by a third.24 Borisov et al.’s large multi-
country study reported that by using BDQ in patients
with complex DR-TB, sputum and culture conversion
rates can exceed 90% and a success rate of 77% can
be achieved.19
Historically, the introduction of new TB drugs has
been a challenge. Fear of potential life-threatening
drug toxicities delayed the use of drugs such as
pyrazinamide and rifampicin after they were discov-
ered as new therapeutic cures for TB.25 During the
roll-out of BDQ and DLM, clinicians were cautious,
as the evidence at the time was not encouraging and
Sirturo, Jannsen’s trade name for BDQ, carried a
‘black box’ warning for patients and healthcare
professionals indicating that the drug poses an
Figure 1 Critical events during the roll-out and scale-up of access to BDQ, India, 2015–2019. DCGI ¼ Drug Controller General of
India; BDQ ¼ bedaquiline; CAP ¼ Conditional Access Programme; ECG ¼ electrocardiogram.
BDQ revamping DR-TB response in India 1069

increased risk of death and arrhythmia. They were
also sceptic because in Diacon et al.’s study, more
patients in the BDQ group than in the placebo group
died, although those who received BDQ had better
culture conversion rates.26
Globally, eligibility restrictions, complicated regu-
latory processes and non-availability of companion
drugs are cited as major barriers to accessing new TB
drugs.27 In India, as in other countries, the absence of
robust recording and reporting systems for AEs and
the inability of the existing surveillance systems to
collect and analyse AE variables were barriers to
accessing new drugs.8 India’s NTP adopted a strategic
approach for providing access to newer drugs.
Regulatory approvals were expedited, eligibility was
expanded over time, availability of companion drugs
was ensured, and systems for aDSM were developed
and deployed. As in other countries, the establish-
ment of pharmacovigilance for patient safety acted as
a catalyst in increasing access to treatment options in
India also.27,28
Ahmed et al.’s meta-analysis proves the importance
of selecting the appropriate OBR on the basis of DST
results29 in improving treatment success and lowering
death rates. Strengthening of TB culture and DST
services was prioritised in India. Building the capacity
of a vast cadre of staff across the country for the
management of MDR-TB using new algorithms,
patient criteria, a follow-up schedule for different
regimens and aDSM was a challenging task. This was
achieved by organising a cascade of training from the
national to the district level and aligning donors and
partners’ support around it.
In-country evidence on tolerability and efficacy
Figure 2 Scale up of access to BDQ in India, from six nodal DR-TB centres in 2016 and 21 centres in
2017 to more than 150 centres across the country in 2018. In 2016, BDQ was introduced at six nodal
DR-TB centres in five states of India: National Institute for TB and Respiratory Disease New Delhi; Rajan
Babu Institute for Pulmonary Medicine and Tuberculosis, New Delhi; Government Hospital of Thoracic
Medicine, Chennai, Tamil Nadu; King Edward Memorial College Group of TB Hospital, Mumbai,
Maharashtra; BJ Medical College and Hospital, Ahmedabad, Gujarat; and Guwahati Medical College,
Guwahati, Assam. In 2017, BDQ access was scaled up to 21 nodal DR-TB centres in the same five
states of India. In 2018, BDQ access was scaled up to cover the entire country through a network of
150 DR-TB centres. BDQ ¼ bedaquiline; DR-TB ¼ drug-resistant tuberculosis.
Figure 3 Quarterwise uptake of BDQ-containing regimens, India, July 2017–March 2019. BDQ¼
bedaquiline.

were systematically collected and analysed. PMDT
guidelines were developed and updated. As the
evidence and experience grew, so did the confidence
among clinicians in the tolerability and efficacy of
BDQ. Therefore, despite reservations regarding the
use of a new drug with potentially serious adverse
drug reactions, the concerted efforts resulted in a
rapid countrywide scale-up of BDQ and the shorter
treatment regimen (STR).
Major policy decisions were made for the early and
increased detection of DR-TB and improved treat-
ment outcomes, including universal drug susceptibil-
ity testing (UDST) and the roll-out of DLM and the
STR for the treatment of MDR-TB in 2018.30 DR-TB
care was decentralised from the 148 nodal DR-TB
centres to 509 additional district-level DR-TB cen-
tres.31. Furthermore, the initiation of treatment was
made possible on an out-patient basis. In February
2019, DLM was made available for use in children
aged 6–17 years across the country.31
To provide a more tolerable, injection-free treat-
ment regimen following the revised classification of
drugs recommended by the WHO,32 the Indian NTP
made the policy decision to introduce the all-oral
longer regimen with BDQ across most of the country.
The WHO’s 2019 rapid communication on DR-TB
treatment now recommends the STR with BDQ,33
and India is now poised to implement this regimen.
USAID’s support in this enormous and ground-
breaking endeavour helped assure the availability of
22 000 patient courses of BDQ for the initial scale-up
while the NTP prepared to include the drug in its
regular procurement mechanisms. In addition, sup-
port from the USAID-funded Challenge TB Project,
implemented by The Union, provided select DR-TB
treatment sites with human resources, ECG ma-
chines, laboratory investigations, linkages for pre-
treatment evaluations, and organised periodic meet-
ings of the Drug Safety Monitoring Committee,
national- and state-level training courses, and, later,
experience-sharing workshops. NTP’s leadership in
aligning partners’ efforts was crucial.
Although BDQ is now recommended as a core drug
in the treatment of MDR-TB,24 Cox et al. have
reported that globally fewer than 20% of persons
estimated to need newer drugs have received them.34
In 2019, an encouraging 48% of eligible patients
received new drugs in India. In India, the notification
of estimated MDR-TB cases in 2019 was almost 51%
compared to 22% in 2016.2
While investing in research, development and the
validation of new tools is important, their rapid
uptake and incorporation into programme settings is
equally critical. The experience with the roll-out and
scale-up of BDQ in the country with the largest TB
burden has paved the way for the continued,
systematic adoption of new tools, especially new
drugs and treatment regimens, in the fight against TB.
CONCLUSIONS
India’s experience underlines the efficacy of BDQ
along with an OBR for better treatment outcomes
among patients with MDR-TB. India’s approach
has been similar to that adopted by other countries
that have harnessed the political commitment of
national and provincial leadership, built capacities
to increase access and closely monitored patients
using ECG testing and enhanced pharmacovigi-
lance.35 India was unique, however, because of the
adaptability of the programme in responding to
local contexts, such as allowing ambulatory treat-
ment and expanding the inclusion criteria to enable
the rapid expansion of access in a short span of
time.
By the end of 2019, cumulatively 9373, 57 040 and
364 patients had received BDQ, the STR and DLM,
respectively. Since many interventions for improving
MDR-TB treatment outcomes in India, such as UDST
for early detection, the STR and countrywide access
to new drugs came into effect in 2018, it is anticipated
that the DR-TB cohort registered in 2018 and later
will have improved treatment outcomes.
Disclaimer: The contents in this article are those of the authors and
do not necessarily reflect the views of the US Agency for
International Development or the US Government.
Conflicts of interest: none declared.
References
1 World Health Organization. Global tuberculosis report, 2019.
WHO/CDS/TB/2019.15. Geneva, Switzerland: WHO, 2019.
2 Seung K J, Keshavjee S Rich M L. Multidrug-resistant
tuberculosis and extensively drug-resistant tuberculosis. Cold
Spring Harb Perspect Med 2015; 5(9): a017863.
3 Migliori G B, et al. MDR/XDR-TB management of patients and
contacts: challenges facing the new decade. Int J Infect Dis
2020; 92S: S15–S25.
4 Lange C, et al. Management of patients with multidrug-
resistant tuberculosis. Int J Tuberc Lung Dis 2019; 23(6): 645–
662.
5 Parmar M M, et al. Unacceptable treatment outcomes and
associated factors among India’s initial cohorts of multidrug-
resistant tuberculosis (MDR-TB) patients under the revised
national TB control programme (2007–2011): evidence leading
to policy enhancement. PLoS One 2018; 13(4): e019.
6 World Health Organization. Policy guidance on interim use of
bedaquiline. Geneva, Switzerland: WHO, 2013.
7 Akkerman O, et al. Surveillance of adverse events in the
treatment of drug-resistant tuberculosis: a global feasibility
study. Int J Tuberc Lung Dis 2019; 83: 72–76.
8 Borisov S, et al. Surveillance of adverse events in the treatment
of drug-resistant tuberculosis: first global report. Eur Respir
Rev 2019; 54: 190152.
9 Udwadia Z F, Ganatra S, Mullerpattan J B. Compassionate use
of bedaquiline in highly drug-resistant tuberculosis patients in
Mumbai, India. Eur Respir J 2017; 49: 1601699.
10 Stop TB Partnership. Gamechanger: USAID and Janssen
Therapeutics announce US$30 million worth of free
bedaquiline to treat drug-resistant TB. Geneva, Switzerland:
Stop TB Partnership, 2014. http://www.stoptb.org/news/
stories/2014/ns14_083.asp
BDQ revamping DR-TB response in India 1071

11 Revised National TB Control Programme. RNTCP guidelines
for use of bedaquiline under Conditional Access Programme.
New Delhi, India: RNTCP, 2015.
12 Revised National TB Control Programme. TB India report, 2016.
New Delhi, India: RNTCP, 2016. https://www.tbcindia.gov.in/
index1.php?lang¼1level¼2sublinkid¼4569lid¼3174
13 Cada D J, et al. Index of drugs. Eur J Med Chem 2016; 22(3).
14 Pontali E, Sotgiu G, D’Ambrosio L, Centis R, Migliori G B.
Bedaquiline and multidrug-resistant tuberculosis: a systematic
and critical analysis of the evidence. Eur Respir Rev 2016; 47:
394–340.
15 Pontali E, et al. Multidrug-resistance tuberculosis and beyond:
an updated analysis of the current evidence on bedaquiline. Eur
Respir Rev 2017; 49: 170014.
16 Pontali E, et al. Cardiac safety of bedaquiline: a systematic and
critical analysis of the evidence. Eur Respir Rev 2017; 50:
170146.
17 World Health Organization. Active tuberculosis drug-safety
monitoring and management (aDSM): framework for
implementation. WHO/HTM/TB. 2015. Geneva, Switzerland:
WHO, 2015.
18 Salhotra V S, et al. Effectiveness and safety of bedaquiline under
conditional access program for treatment of drug-resistant
tuberculosis in India. Indian J Tuberc 2019;
19 Borisov S E, et al. Effectiveness and safety of bedaquiline
containing regimens in the treatment of MDR- and XDR-TB.
Eur Respir Rev 2017; 49: 170038.
20 Sarin R, et al. Initial experience of bedaquiline implementation
under the National TB Programme at NITRD, Delhi, India.
Indian J Tuberc 2019; 66(1): 209–213.
21 Barvaliya S B, Desai M K, Panchal J R Solanki R N. Early
treatment outcome of bedaquiline plus optimised background
regimen in drug resistant tuberculosis patients. Indian J Tuberc
2020; 67 29–37.
22 Revised National TB Control Programme. Guidelines for
programmatic management of drug resitant TB. New Delhi,
India: RNTCP, 2017.
23 Lu X, et al. Health outcomes of bedaquiline in the treatment of
multidrug-resistant tuberculosis in selected high burden
countries. BMC Health Serv Res 2017; 17(1): 87.
24 Cox V, et al. An activist’s guide to bedaquiline. Treatment
Action Group, 2018. https: //www.treatmentactiongroup.org/
wp-content/uploads/2013/03/BDQ_guide_10_5_18.pdf
25 Murray J F, Schraufnagel D E Hopewell P C. Treatment of
tuberculosis: a historical perspective. Ann Am Thorac Soc
2015; 12(12): 1749–1759.
26 Diacon A H, et al. Multidrug-resistant tuberculosis and culture
conversion with bedaquiline. N Engl J Med 2014; 371(8): 723.
27 Rodriguez C A, et al. Barriers and facilitators to early access of
bedaquiline and delamanid for MDR-TB: a mixed-methods
study. Public Health Action 2019; 9(1): 32–41.
28 Borisov S E, et al. Outcomes of patients with drug-resistant-
tuberculosis treated with bedaquiline-containing regimens and
undergoing adjunctive surgery. J Infect 2019; 78(1): 35–39.
29 Ahmad N, et al. Treatment correlates of successful outcomes in
pulmonary multidrug-resistant tuberculosis: an individual
patient data meta-analysis. Lancet 2018; 392(10150): 821–
834.
30 Central TB Division, Ministry of Health and Family Welfare.
Guidelines for use of delamanid (Dlm) in the treatment of drug-
resistant TB (DR-TB) in India. New Delhi, India: MoHFW,
2018. https://tbcindia.gov.in/index1.php?lang¼1level¼1
sublinkid¼4150lid¼2794
31 Central TB Division, Ministry of Health and Family Welfare.
India TB Report, 2019. New Delhi, India: MoHFW, 2019.
http://tbcindia.nic.in/WriteReadData/IndiaTBReport2019.pdf
32 World Health Organization. Guidelines for treatment of MDR
TB patients 2019. Geneva, Switzerland: WHO, 2019. https://
www.who.int/tb/publications/2019/consolidated-guidelines-
drug-resistant-TB-treatment/en/
33 World Health Organization. Rapid communication: key changes
to treatment of multidrug- and rifampicin-resistant tuberculosis
(MDR/RR-TB). Geneva, Switzerland: WHO, 2019.
34 Cox V, et al. Global programmatic use of bedaquiline and
delamanid for the treatment of multidrug-resistant
tuberculosis. Int J Tuberc Lung Dis 2018; 22(4): 407–412.
35 Schnippel K, et al. Persistently high early mortality despite rapid
diagnostics for drug-resistant tuberculosis in South Africa. Int J
Tuberc Lung Dis 2017; 1(10): 1106–1111.

R É S U M É
C O N T E X T E : Affronter la TB en Inde est crucial pour
atteindre les objectifs mondiaux. Avec l’accélération des
réseaux de diagnostic et la disponibilité des nouveaux
médicaments TB, l’Inde a eu l’occasion d’améliorer la
détection et les résultats du traitement de la TB
pharmacorésistante (DR-TB).
O B J E C T I F : Documenter la manière dont l’introduction
des nouveaux médicaments et protocoles aident l’Inde à
améliorer la prise en charge des patients DR-TB.
S C H É M A : En 2016, le Programme national TB d’Inde
(NTP) a introduit la bédaquiline dans le cadre d’un
programme d’accès conditionnel (BDQ-CAP) dans six
sites après avoir fourni une formation intensive et des
systèmes de renforcement des tests de laboratoire, une
évaluation avant le traitement et un suivi et une gestion
actifs de la sécurité des médicaments (aDSM).
R É S U LTAT S : Une analyse d’intérim a reflété des taux de
conversion de culture plus précoces et meilleurs avec
83% des 620 patients qui ont eu une conversion après un
délai médian de 60 jours. Ont été rapportés 248 effets
secondaires graves, notamment 73 décès (12%) et 100
problèmes de cardiotoxicité (16,3%). Encouragés par les
preuves d’innocuité et d’efficacité de la bédaquiline, le
NTP a pris des mesures pour en étendre
systématiquement l’accès afin de couvrir toute la
population d’ici 2018.
C O N C L U S I O N : L’approche prudente mais focalisée
utilisée pour introduire le nouveau médicament sous
BDQ-CAP a ouvert la voie à l’introduction rapide du
délamanide, ainsi qu’à un protocole de traitement plus
court et à un protocole entièrement oral pour la DR-
TB.
R E S U M E N
M A R C O D E R E F E R E N C I A: Abordar la TB en la India es
primordial para alcanzar las metas mundiales. Al ampliar
las redes diagnósticas y la disponibilidad de nuevos
fármacos contra la TB, la India tuvo la oportunidad de
mejorar la detección y los desenlaces terapéuticos de la
TB resistente a los medicamentos (DR-TB).
O B J E T I V O: Documentar la forma como la introducción
de fármacos y esquemas terapéuticos nuevos está
ayudando a que la India mejore la atención de los
pacientes con DR-TB.
M É T O D O: En el 2016, el Programa Nacional contra la
Tuberculosis de la India (NTP) introdujo la bedaquilina
en el marco de un Programa de Acceso Condicional
(BDQ-CAP) en seis centros, tras impartir capacitación
exhaustiva y fortalecer los sistemas de pruebas de
laboratorio, la evaluación anterior al tratamiento, la
farmacovigilancia activa (aDSM) y el seguimiento.
R E S U LT A D O S: Un análisis intermedio reveló
conversiones del cultivo más tempranas y mejores
tasas de conversión, hasta un 83% en 620 pacientes,
con una mediana del lapso de conversión de 60 dı́as.
Se comunicaron 248 reacciones adversas graves,
incluidas 73 defunciones (12%) y 100 episodios de
cardiotoxicidad (16,3%). El NTP, estimulado por la
evidencia de seguridad y eficacia de la bedaquilina,
emprendió medidas para ampliar sistemáticamente
su acceso, hasta cubrir a toda la población en el
2018.
C O N C L U S I Ó N: La estrategia prudente y dirigida que
se utilizó para introducir un nuevo fármaco en el
marco del BDQ-CAP facilitó la introducción rápida
del delamanid y también del régimen acortado y el
tratamiento por vı́a oral exclusiva contra la DR-
TB.
BDQ revamping DR-TB response in India i

Strengthened capacity of India´s bedaquiline Conditional Access Programme for introducing new drugs and regimens.pdf

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Similar to Strengthened capacity of India´s bedaquiline Conditional Access Programme for introducing new drugs and regimens.pdf

Similar to Strengthened capacity of India´s bedaquiline Conditional Access Programme for introducing new drugs and regimens.pdf (20)

Recently uploaded

Recently uploaded (20)

Strengthened capacity of India´s bedaquiline Conditional Access Programme for introducing new drugs and regimens.pdf