Background
The emergence of drug-resistant tuberculosis is a major threat to global tuberculosis care and control. WHO estimates that about 450,000 new multidrug-resistant tuberculosis (MDR-TB) cases occurred in the world in 2012. Of these, only 94000 were reported to WHO, largely as a result of critical gaps in diagnostic and treatment capacity in most countries. Furthermore, 92 countries have now reported at least one case of extensively drug-resistant tuberculosis (XDR-TB) (Global Report 2013).
Current treatment regimens for drug-resistant TB are far from satisfactory. Whereas most drug-susceptible TB patients can usually be cured 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 2010, only 48% were treated successfully, as a result of high frequency of death (15%) and loss to follow-up (28%) commonly associated with adverse drug reactions and high costs associated with adherence to treatment. In addition, it is estimated that up to a third of MDR-TB cases may have strains with additional resistance to fluoroquinolones and/or injectable drugs (aminoglycosides or capreomycin), rendering their treatment even more difficult, with recourse to highly toxic drugs. Finally, the global deployment of new, rapid diagnostics for drug resistance, such as the Xpert MTB/RIF assay, has increased the demand for treatment of MDR-TB patients, that has not been matched by a similar expansion in the provision of appropriate treatment for diagnosed cases. While 94,000 cases were reported to WHO as having been diagnosed in 2012, only 77,000 patients were known to have been placed on treatment for MDR-TB. The increased global scale-up of rapid tests to diagnose such cases is bound to make this gap even wider in the coming years. The lack of effective and affordable drugs for the treatment of MDR-TB is known to weigh heavily among the reasons why programmes cannot scale up their treatment efforts to the required level.
The landscape of drug development for treatment of TB has evolved dramatically over the last ten years, and novel drugs are presently or soon entering Phase III trials for the treatment of MDR-TB. Dossiers have been submitted to stringent regulatory authorities (SRAs) under procedures of “accelerated” or “conditional” approval for marketing these new drugs. Among these, delamanid, a nitro-imidazole, has been recommended for conditional marketing authorisation by the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) on the 26th November 2013. For this reason, WHO aims to evaluate the added value of this compound within the context of existing guidelines on programmatic management of MDR-TB and issue interim guidance on the use of delamanid as and if appropriate.
Overall Objective
To evaluate the added benefit of a newly available drug, delamanid, to the treatment of MDR-TB, a life-threatening form of tuberculosis, and provide recommendation to WHO for provision of interim guidance to countries on its use in conjunction with other second-line drugs used in MDR-TB treatment as and if appropriate.
