The use of short regimens for treatment of multidrug-resistant tuberculosis
10 August 2012 | The current WHO guidelines on treatment regimens for MDR-TB recommend an intensive phase of treatment of 8 months and a total duration of treatment of 20 months for most patients(1). The guidelines were developed following the GRADE process for guideline development that has been adopted by WHO, and recommendations were based on an analysis of more than 9,000 cases treated in observational studies. The results from an observational study in Bangladesh showed much better rates of treatment success using regimens having a duration of 12 months or less compared with those usually achieved when the longer regimens are used (2). However, there is much less evidence on the effectiveness and safety of these so-called “short-regimens” compared with regimens lasting 20 months.
WHO’s position is that regimens which are markedly different from the ones which represent the current norm and have undergone GRADE review should only be used within the context of research and under close monitoring for a period of at least 12 months beyond the end of treatment. This follow-up after treatment completion is aimed at early identification of those patients who may have a high risk of relapse and acquired resistance. Proper attention to drug regulatory and ethical issues will be needed to facilitate the gathering of additional evidence that can be used for future updates of current WHO guidelines on the treatment of MDR-TB. Until sufficient evidence is available to inform a policy update, WHO is advising countries to introduce short MDR-TB treatment regimens only in projects that adhere to the following criteria:
- approval of the project by a national ethics review committee, ahead of any patient enrolment;
- delivery of treatment under operational research conditions following international standards (including Good Clinical Practice and safety monitoring), with the objective of assessing the effectiveness and safety of these regimens;
- monitoring of the MDR-TB programme using short regimens, and its corresponding research project, by an independent monitoring board set up by and reporting to WHO.
Countries planning to use short regimens for MDR-TB treatment according to the criteria listed above will be offered assistance to develop the required operational research and programme management capacity if this is not yet available. Support from WHO for such assistance should be sought on a country-by-country basis prior to embarking on the use of short MDR-TB regimens. Countries planning to request funding from the Global Fund to Fight AIDS, Tuberculosis and Malaria to implement programmes based on these short regimens should approach WHO to obtain confirmation that the criteria listed above are properly applied, ahead of any application for funding to the Global Fund.
- Guidelines for the programmatic management of drug-resistant tuberculosis, 2011 Update. (WHO/HTM/TB/2011.6). Geneva, World Health Organization. 2011.
- Van Deun A, Maug AK, Salim MA, Das PK, Sarker MR, Daru P, Rieder HL. Short, highly effective, and inexpensive standardized treatment of multidrug-resistant tuberculosis. Am J Respir Crit Care Med. 2010 Sep 1;182(5): 684–92.