WHO removes injectable drugs from MDR regimensApril 9, 2019
The WHO has revamped the treatment guidelines for MDR and rifampicin-resistant (RR-TB) even as multi-drug resistance poses a threat to the End TB Strategy.
The guidance, based on a review of the recent evidence on priority questions in MDR/RR-TB treatment, was formulated by the Guideline Development Group (GDG).
“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. Fully oral regimens should thus become the preferred option for most patients,” stated Dr Tereza
Kasaeva, Director of WHO’s Global TB Programme.
The evidence included the recently completed phase 3 trials of delamanid (Otsuka’s Trial 213) and the standardised 9-12-month shorter MDR-TB regimen (STREAM Stage 1), as well as individual data for 13,100 patients 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 the use of bedaquiline and delamanid in children.
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. Shorter regimens for MDR 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 like the 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 people living with HIV (PLHIV) and to MDR/RR-TB patients who have additional resistance to fluoroquinolones or other agents.
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.