Tuberculosis (TB)

WHO updates its treatment guidelines for multidrug- and rifampicin-resistant tuberculosis

Maxim Dondyuk

Multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB) threaten global progress towards the targets of the End TB Strategy set by the World Health Organization (WHO). In 2018, WHO convened a multidisciplinary team of external experts with experience in different aspects of tuberculosis care and affected individuals to update its MDR/RR-TB treatment policy.

This Guideline Development Group (GDG) used the GRADE approach (Grading of Recommendations, Assessment, Development and Evaluation) to formulate the new guidance based on a review of the most recent evidence on priority questions in MDR/RR-TB treatment. The evidence included the recently completed Phase III trials of delamanid (Otsuka’s Trial 213) and the standardized 9-12 month shorter MDR-TB regimen (STREAM Stage 1), as well as individual data for 13,100 patient treated with longer MDR-TB regimens in 40 countries and over 2,600 patients treated with the shorter MDR-TB regimen from 15 countries. Additional trial data from patients under 18 years of age allowed a review of recommendations for use of bedaquiline and delamanid in children.

“The new WHO recommendations, based on the most recent available evidence, signal an important departure from previous approaches to treat MDR/RR-TB. Injectable agents are no longer among the priority medicines when designing longer MDR-TB regimens and fully oral regimens should thus become the preferred option for most patients”, stated Dr Tereza Kasaeva, Director of WHO’s Global TB Programme. Fluoroquinolones (levofloxacin or moxifloxacin), bedaquiline and linezolid are strongly recommended for use in longer regimens, which are completed with other medicines ranked by their relative balance of effectiveness to potential toxicity.

The shorter MDR-TB regimen may be offered to eligible patients who agree to a briefer treatment that may, however, be less effective than an individualized longer regimen and that requires a daily injectable agent for at least four months. Regimens that vary substantially from the recommended composition and duration (e.g. a standardized 9-12 month shorter MDR-TB regimen in which the injectable agent is replaced by bedaquiline) can be explored under operational research conditions.

The recommendations apply generally to children and adults, to PLHIV and to MDR/RR-TB patients who have additional resistance to fluoroquinolones or other agents, subject to specific conditions. Bedaquiline may now be given to children aged 6 years and more and delamanid from 3 years of age. Supportive measures to improve diagnostics and other programmatic components will be critical. Ahead of enrolment on MDR-TB treatment, all patients should be appropriately counselled to enable participatory decision-making. Patient-centred support for medication adherence and active TB drug safety monitoring and management (aDSM) are essential for anyone starting an MDR-TB regimen.

In early 2019, consolidated drug-resistant TB treatment guidelines, complemented by a new edition of WHO’s Companion handbook for the programmatic management of drug-resistant tuberculosis will be released.

WHO and partners urge countries to take bold actions so that patients can benefit from the new, more effective and safer treatments as soon as possible, and stand ready to provide all necessary technical support.