NHS England has published a new Clinical Commissioning Policy making bedaquiline (Sirturo) routinely available on the NHS as part of an appropriate combination regimen for the treatment of pulmonary multi-drug resistant tuberculosis (MDR-TB) in adult patients when an effective treatment regimen cannot otherwise be composed for reasons of resistance or tolerability. This new policy means that clinicians in England will be able to access and prescribe bedaquiline more easily, via a registry, in order to monitor its use as well as patient outcomes.
Bedaquiline is the first new medicine for MDR-TB with a novel mechanism of action to be introduced for almost 50 years. Phase 2 studies have shown that bedaquiline, as part of an appropriate combination regimen, can shorten time to culture conversion (an indicative measure assessing when the patient is responding to therapy) in adult patients with pulmonary MDR-TB. After 24 weeks of treatment, the median time to culture conversion was significantly shorter for the bedaquiline group (83 days) compared to the placebo group (125 days). In addition, treatment with bedaquiline continued to result in a significantly improved culture conversion rate at week 120 compared to the placebo-treated group.
Furthermore, when final data are translated to the WHO-recommended treatment outcome definitions, the proportion of patients defined as cured at 120 weeks was 57.6% in the bedaquiline arm vs. 31.8% in the placebo arm (p=0.003). The most frequent adverse events (AEs [observed in >10% of patients]) during treatment with bedaquiline were nausea (35.3% in the bedaquiline group vs 25.7% in the placebo group), arthralgia (29.4% vs 20.0%), headache (23.5% vs 11.4%), vomiting (20.6% vs 22.9%) and dizziness (12.7% vs 11.4%). These are similar to those commonly reported in patients with TB who receive second-line treatment for MDR-TB, and those leading to the discontinuation of bedaquiline were uncommon.
Professor Onn Min Kon, Respiratory Physician commented: "The provision of a commissioning policy for these promising new drugs in the treatment of multi-drug resistant tuberculosis is welcomed by clinicians. This now allows clear criteria and funding for specialist clinicians to prescribe these new agents in a group of patients with the most complex and serious form of tuberculosis. Such access is critical for situations when standard recommended therapies for drug resistance are not suitable because of resistance patterns to the most effective drugs or because of side effects that may be seen in some patients. The addition of these to a suboptimal regime will potentially contribute to a reduction in periods of infectiousness and improve outcomes for the patient."
The new NHS England policy was based on a needs assessment highlighting that cases of TB in the UK are high compared to most other Western European countries. Out of a total 7,892 cases of TB in the UK in 2013, London accounted for the highest proportion (2,985 cases, 41%) followed by the West Midlands (981 cases, 13.4%). The assessment also cited an increase in cases of MDR-TB in the UK, rising from 28 cases in 2000 to 89 cases in 2012. Furthermore, cases were predicted to increase based on the global epidemiology of MDR-TB and current patterns of migration. The World Health Organization (WHO) estimates that up to half a million new cases of MDR-TB occur each year globally and that more than two million people will be infected with MDR-TB between 2011 and 2015. Due to the infectious nature of the disease, achieving faster time to culture conversion and resultant cure in patients with MDR-TB is vital in preventing further transmission, aligning to the WHO global strategy for TB prevention, care and control for 2015 onwards.