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Recommendations
- 4.1.
In the treatment of patients with MDR-TB, an intensive phase of 8 months is suggested for most patients, and the duration may be modified according to the patient's response to therapy (conditional recommendation, ⊕○○○/very low quality evidence).
- 4.2.
In the treatment of patients newly diagnosed with MDR-TB (i.e. not previously treated for MDR-TB), a total treatment duration of 20 months is suggested for most patients, and the duration may be modified according to the patient's response to therapy (conditional recommendation, ⊕○○○/very low quality evidence).
Evidence
The evidence used to derive recommendations on the duration of treatment was based on an analysis of the same individual patient data collected and described in Section 3 above. All data were from observational studies, and the quality of evidence was classified as very low. Attempts to control for selection bias and confounding in this review are unlikely to have adjusted for all important factors, and patients who receive longer therapy may be those who are more sick. Patients with XDR-TB were also excluded from the analysis. The findings may not be generalizable to all populations in settings with high or low prevalence of drug resistance or with different levels of resources.
Summary of findings
The analysis provided evidence for an association between treatment success and the total length of treatment and the length of the intensive phase. The trend in relative risk for cure over successive months of treatment was studied to determine the optimal minimum duration for both total treatment and the intensive phase. The adjusted relative risk for cure peaked at an intensive phase lasting between 7.1 and 8.5 months (see also Table 8 and Annex 2). For total treatment duration, the peak occurred between 18.6 and 21.5 months for patients who had no previous MDR-TB treatment. The peak occurred later in patients who had been treated for MDR-TB (27.6–30.5 months), but no clear incremental trend was observed in these patients and the number of observations was far fewer than for those who had no previous MDR-TB treatment.
Table 8
Odds ratios of treatment success by duration of intensive phase and total treatment.
Most patients may be expected to receive this length of treatment but in some it may have to be modified depending on their bacteriological status and other indicators of treatment progress.
The recommendations have thus changed from those contained in the 2008 emergency update, which recommended a duration of treatment for MDR-TB patients based on the use of a parenteral agent for a minimum of 6 months and at least 4 months past culture conversion, and a minimum total length of treatment of 18 months after culture conversion. The new recommended duration of intensive phase is 2 months longer than the minimum previously recommended. There is, however, no substantial difference in the total length of treatment being recommended because conversion typically takes a few months to occur. The data used for this analysis could not inform whether a minimum duration of the intensive phase after conversion was a determinant of outcome.
Benefits
When selecting the duration of treatment, the analysis allowed a choice to be made within a narrow margin of a few consecutive months, thus reducing the likelihood of prolonging treatment unnecessarily. While shorter regimens would confer clear benefits and be preferred, evidence for the effectiveness of a 9-month regimen for MDR-TB patients has up to now been limited to data from one setting (included in this review) (16). The Guideline Development Group supports further investigation of the safety and effectiveness of shorter regimens using the randomized controlled trial design in order to strengthen evidence for their potential use for the treatment of drug-resistant TB.
Risks
The risk of serious adverse events (SAE) was observed to increase beyond the first 12 months of treatment but was not correlated with the length of the intensive phase beyond the first 2 months. These trends should be interpreted with caution as they may be confounded by the number of drugs used (independently correlated with SAE) as well as features of the illness process not accounted for in the measure of extent of disease used in this analysis.
Values and preferences
A high value was placed on outcomes such as preventing death and transmission of MDR-TB as a result of failed treatment as well as avoiding harms and minimizing use of resources. The group placed a lower value on reducing the duration of treatment, while acknowledging that many patients may place a higher value on avoiding a long treatment course due to burden and inconvenience.
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Publisher
World Health Organization, Geneva
NLM Citation
Guidelines for the Programmatic Management of Drug-Resistant Tuberculosis: 2011 Update. Geneva: World Health Organization; 2011. 4, Duration of second-line anti-tuberculosis regimens.