The World Health Organization (WHO) has made key changes in the recommended treatment for multidrug-resistant tuberculosis (MDR-TB) that prioritize newer medications and oral regimens over injectable drugs.
In a rapid communication published Aug 17, the WHO summarized the changes, which include a new priority ranking of available drugs for MDR-TB treatment based on the balance of effectiveness and harms and a preference for oral agents. The drugs in the preferred treatment regimen now include bedaquiline, a novel oral TB drug that was approved by the US Food and Drug Administration in 2012 and is currently used in 89 countries, but on a limited basis. Delaminid, another newer oral medication, is also on the list of recommended drugs.
Two injectable drugs that have been associated with side effects and increased risk of treatment failure—kanamycin and capreomycin—are no longer recommended.
WHO officials say they hope the revised recommendations will improve treatment outcomes and the quality of life of patients with MDR-TB, which has become a major obstacle in the global campaign against tuberculosis. The agency estimates about 600,000 cases of MDR-TB or rifampicin-resistant TB emerge each year, and that roughly 240,000 die from drug-resistant forms of the disease. Only 54% of the MDR-TB patients who start treatment are successfully treated, in part because of the length and toxicity of the treatment.
"The treatment landscape for patients with MDR-TB will be dramatically transformed for the better with the announcement today," Soumya Swaminathan, MD, WHO deputy director-general for programmes, said in a WHO press release.
Advocates praise the new recommendations
The revised treatment recommendations are based on data from 50 studies of longer MDR-TB regimens involving 12,000 patients, new data from countries using bedaquiline, and the results of a phase 3 trial of delaminid. Data on shorter regimens was also included. Much of the data was generated through the WHO's February 2018 request for patient data from researchers, industry, and national TB programs.
The recommendations regroup the drugs used in longer MDR-TB regimens, which last 18-20 months, into three categories, with bedaquiline in Group A, along with linezolid and levofloxacin or moxifloxacin. Group B medicines include clofazimine and cycloserine or terizidone. Group C drugs, which are to be used only when agents in groups A and B can't be used, include delaminid, ethambutol, pyrazinamide, imipenem-cilastatin or meropenem, amikacin, ethionamide or prothionamide, and p-aminosalicylic acid. Only two of the medications (amikacin and imipenem-cilastatin/meropenem) are injectable.
Jennifer Furin, MD, PhD, an infectious disease clinician at Harvard Medical School who's been combating MDR-TB since 1995, called the new recommendations "revolutionary."
"For the first time ever, an all-oral treatment regimen will be available to treat the majority of people with drug-resistant TB," Furin told CIDRAP News in an email. "So many people have suffered permanent side effects—most notably hearing loss—from the injectables used in the treatment of MDR-TB, and the new recommendations will allow people to be spared this miserable side effect."
Advocacy and global health groups, including the TB Alliance, the Global TB Community Advisory Board, Treatment Action Group (TB CAB), and Doctors Without Borders (MSF) also praised the recommendations for prioritizing newer oral medications over injectable drugs. But MSF and TB-CAB urged Johnson and Johnson, maker of bedaquiline, to make the drug more affordable and accessible.
"Governments and treatment providers should not waste another minute and should urgently make sure people can access optimal treatments including bedaquiline," Dr Mercedes Tatay, MD, MSF's international medical secretary, said in an MSF press release. "This means J&J needs to lower the price of the drug and ensure it is available for every person who needs it."
Furin agreed that ensuring greater access to the drugs will be critical to the success of the new recommendations. The WHO estimates that only 22% of eligible MDR-TB patients are being treated with the currently recommended regimen.
"We now need to make sure that all the countries procure the medications in the WHO's new groupings—especially bedaquiline, clofazimine, and linezolid—and that countries are given strong support by donors, technical partners, and national organizations to implement these changes in an optimal yet timely way," she said.
Global access to drugs for MDR-TB treatment is likely to be among the topics of discussion at the first ever United Nations High-level Meeting on TB, to be held on Sep 26 in New York.
The WHO says a more detailed version of the new guidelines will be provided at the end of the year, but is urging national TB programs to start preparing for these changes now. The agency says it's establishing a task force to help countries update their national TB guidelines.
Aug 17 WHO Rapid Communication
Aug 17 WHO press release
Aug 17 MSF press release