The emergence of drug resistance is a major threat to global tuberculosis (TB) care and control. The World Health Organization (WHO) estimates that up to half a million cases of multidrug-resistant tuberculosis (MDR-TB) cases (i.e. resistant to, at least, rifampicin and isoniazid) occur each year globally.⁶ Of these, less than 20% were reported to WHO, largely as a result of critical gaps in diagnostic and treatment capacity in most countries. Furthermore, 84 countries have now reported at least one case of extensively drug-resistant tuberculosis (XDR-TB), a form of TB that is resistant to at least four of the core anti-TB drugs (rifampicin, isoniazid, fluoroquinolones and second-line injectable agents), and associated with high mortality, particularly among people living with human immunodeficiency virus (PLHIV).

The global deployment of new, rapid diagnostic tests for drug resistance, such as the Xpert MTB/RIF assay, is increasing the demand for treatment of MDR-TB patients. Current treatment regimens for drug-resistant TB are far from satisfactory. Whereas most drug-susceptible TB patients can usually be treated successfully with a 6-month course of treatment, in most MDR-TB cases a treatment duration of 20 months or more is used, requiring the daily administration of drugs that are more toxic and less effective than those used to treat drug-susceptible TB. Among MDR-TB patients started on treatment globally in 2009, only 48% were treated successfully, as a result of high frequency of mortality (15%) and loss to follow-up (28%), commonly associated with adverse drug reactions, among other factors.⁷ In a subset of 200 XDR-TB patients in 14 countries, treatment success only reached 33% overall and 26% of cases died. Effective new drugs and treatment regimens are therefore urgently needed to improve safe and effective treatment to reduce patient suffering and deaths.

The landscape of TB drug development has evolved dramatically over the past ten years, and novel drugs are presently, or will soon be, entering Phase III trials for the treatment of MDR-TB. Among these, the bedaquiline compound, proposed for use in the treatment of MDR-TB, has been granted license by the United States Food and Drug Administration (US-FDA) in December 2012. Files have been submitted to a number of other national regulatory authorities, which are currently being evaluated under procedures of ‘accelerated’ or ‘conditional’ approval based on early (Phase IIb) clinical data. Several WHO Member States have requested the organization to provide interim advice on the use of bedaquiline in MDR-TB treatment. For these reasons, WHO convened an Expert Group (EG) meeting from 29th to 30th January 2013 in Geneva, Switzerland to review the available evidence on the efficacy, safety and effectiveness of this new drug for the treatment of MDR-TB, and to recommend whether WHO interim guidance on the use of this drug as part of the treatment of MDR-TB is warranted.

It is acknowledged that developing interim guidance on the use of a new TB drug on the basis of Phase IIb data only is a novel step by WHO, and one made in response to requests from WHO Member States for specific guidance. Issuing interim guidance carries with it the responsibility of ensuring that it provides specific recommendations on the conditions for the use of the drug, which reflect the limited data that is currently available. It will also be necessary for WHO to review, revise or update the interim guidance as additional substantive data on efficacy and safety of bedaquiline become available. Acceleration of Phase III trials and completion at the earliest opportunity is imperative, as is timely analysis of emerging operational data on the use of the drug. It should also be noted that, in the absence of interim guidance from WHO, uncontrolled and potentially irresponsible use of the drug may adversely affect TB care and control efforts overall – potentially prompting the emergence of bedaquiline resistance and the possible loss of the first new TB drug in over 40 years.