TB CAB and TAG Welcome WHO Recommendation of Injectable-Free Regimens for the Treatment of RR/MDR-TB

By Erica Lessem | 17 Aug, 2018

*The TB CAB and TAG welcome WHO recommendation of injectable-free regimens
for the treatment of RR/MDR-TB*
*The WHO, Ministries of Health and Finance, donors, implementers, technical
assistance providers, civil society, and communities must work together to
ensure rapid implementation*

*17 August, 2018* – The Global Tuberculosis Community Advisory Board (TB
CAB) and Treatment Action Group (TAG) welcome the new Word Health
Organization (WHO) recommendation
of injectable-free regimens for the treatment of rifampicin- and
multidrug-resistant tuberculosis (RR/MDR-TB). The new WHO recommendation
ushers in a long-awaited era in which medicines with strong evidence for
their use replace toxic medicines with little evidence of effectiveness.

As announced today in a WHO Rapid Communication
<http://www.who.int/tb/publications/2018/rapid_communications_MDR/en/>, the
new preferred standard treatment regimen for RR/MDR-TB is composed of
bedaquiline, linezolid, levofloxacin (or moxifloxacin), and cycloserine and
clofazimine. The injectable agents, which showed poor efficacy in addition
to high toxicity, have been relegated to use only when a regimen with 4–5
effective drugs cannot otherwise be composed. Kanamycin and capreomycin are
no longer recommended.

 “The TB CAB and TAG commend the WHO for undertaking the development of
consolidated treatment guidance, and issuing an open call for data to do
so. We also acknowledge the tremendous contributions of the country
programs, drug sponsors, and research teams that responded to the call and
enabled the development of evidence-based treatment guidelines,”
acknowledged Patrick Agbassi and Carolina Morán Jara, co-chairs of the TB
CAB. “We urge all actors—including country governments, donors,
implementing partners, technical assistance providers, civil society, and
communities—to work together to rapidly transition TB programs to the new
longer regimens.”

 “The new longer regimens should end the unnecessary and unethical
subjugation of patients to the avoidable disability, pain, and other
serious risks associated with the injectable agents,” said Marcus Low,
Technical Co-Lead of the TB CAB. “However, there are multiple challenges
with the WHO communication. The continued recommendation of the shorter
regimen is perplexing given the demotion of five of the seven medicines
that compose it, and that a phase III randomized controlled trial showed
the shorter regimen was not as good as the previously recommended longer
regimen. This raises concern that the recommendation for continued use of
the shorter regimen is not grounded in evidence, nor in patients’ best
interests.” The new guidelines also highlight the importance of on-going
research and development efforts to inform the optimal duration of
treatment with the new preferred regimens.

“The new guidelines challenge global and national actors to ensure that all
affected have access to medicines needed to benefit from the new longer
regimens,” said Lindsay McKenna, Senior TB/HIV Project Officer of Treatment
Action Group and Coordinator of the TB CAB. The new recommendation
underscores the urgency of ensuring the affordability of the recommended
medicines, especially bedaquiline, clofazimine, and linezolid. We reiterate
the TB CAB’s previous call
for Janssen Pharmaceuticals—a division of Johnson & Johnson— to lower the
price bedaquiline to US$32 per month. Further transparent, pre-set
volume-based reductions must be negotiated with global partners, including
civil society.

Also essential to rolling out the new longer regimens is ensuring that
tests and other necessary monitoring equipment are widely available. “Given
the importance of drug resistance profiling to implementing the new
treatment guidelines, the ability to detect drug resistance must be rapidly
scaled up,” remarked Khairunisa Suleiman, Technical Co-Lead of the TB CAB.
“In addition to scaling up existing drug susceptibility testing (line probe
assays and liquid culture), there is also urgent need for sequencing
technologies (which can detect multiple genetic mutations that confer
resistance to drugs) adapted for use in low resource settings and clear WHO
guidance on their use.” Tests and training to monitor for nerve and liver
damage, changes in the heart’s electrical activity and in the body’s
potassium levels, depression, and psychosis will be critically important to
ensuring that patients can safely complete treatment with the new preferred

In sum, we laud the recommendation for the new longer regimens, and urge
their rapid implementation, which will require access to appropriate
medicines, tests, and monitoring. We remain concerned by the continued
recommendation of the shorter regimen.

The mixed messages resulting from the Guideline Development Group (GDG)
meeting held in July 2018 reinforce the concerns raised by civil society
and community groups
regarding the WHO guideline development process. We appreciate the
receptivity of the WHO, and in particular Global TB Program Director Tereza
Kasaeva, to addressing these. We look forward to future collaboration to
resolve remaining issues, which include 1) transparency regarding the
process and criteria by which the WHO selects GDG members; 2) the need for
increased GDG member capacitation to allow for optimal participation in GDG
meetings; 3) reforms to the WHO’s conflict of interest policy; 4) the
establishment of a mechanism for public comment on the selection and
framing of the questions that inform what data are collected and how they
are analyzed (PICO questions); 5) the speed and regularity at which
guidelines are updated, especially in response to emerging evidence, and
how to best integrate updates; 6) the inconsistent and undue consideration
of cost in forming recommendations; 7) the need for more regular and
independent evaluations of WHO guidance documents via end-user surveys; and
8) harmonization of the expectations of the WHO and stringent regulatory
authorities regarding quality and outcomes of interest for phase III TB

# # #

*The Global TB Community Advisory Board (TB CAB) *is a group of strong,
research-literate community activists from HIV and TB networks in Asia,
Europe, Africa, and North and South America. Founded in 2011, the TB CAB
acts in an advisory capacity to product developers and institutions
conducting clinical trials of new TB drugs, regimens, diagnostics, and
vaccines, and provides input on study design, early access, regulatory
approval, post-marketing, and implementation strategies. The TB CAB is
dedicated to increasing community involvement in TB research and access to
tools to fight TB, and mobilizing political will.

*Treatment Action Group (TAG) *is an independent, activist, and
community-based research and policy think tank fighting for better
treatment and prevention, a vaccine, and a cure for HIV, TB, and hepatitis
C virus (HCV). TAG works to ensure that all people with HIV, TB, and HCV
receive lifesaving treatment, care, and information. We are science-based
treatment activists working to expand and accelerate vital research and
effective community engagement with research and policy institutions.

*Contact Us:* Treatment Action Group, 90 Broad Street, Suite 2503, New
York, New York 10004
212-253-7922. .
<> This year marks TAG's 26th year
fighting for life-saving medications for people living with, and at risk
for, HIV, TB, and HCV. Please consider supporting this work by making a