New, more effective medicines replace painful daily shots, drugs causing psychosis, permanent hearing loss; TB and medical communities welcome change, say recommended drugs must be accessible, affordable
Saying rates of cured cases of drug-resistant tuberculosis could be increased with access to an oral regimen of newer, more effective and less toxic medicines, the World Health Organization today released a summary of significant changes it will make to TB treatment guidelines later this year, urging national health agencies to prepare for them now.
The changes, summarized in a WHO Rapid Communication: Key changes to treatment for multidrug- and rifampicin resistant tuberculosis (MDR/RR-TB), include prioritizing the use bedaquiline, approved by the U.S. Food and Drug Administration for treatment of drug-resistant tuberculosis in 2012, but still inaccessible to the vast majority of patients with disease that does not respond to older, more toxic medicines. The recommendations also include the use of delamanid, the other of only two new drugs to receive regulatory approval in the last decade, in another regimen. Along with those changes and the prioritization of other newer or repurposed drugs, WHO has taken two drugs off their list of recommended treatments — kanamycin and capreomycin, both dating back to the middle of the last century, administered in painful daily injections, and linked to severe and permanent side effects that include hearing loss in from a quarter to more than half of patients receiving it. Those side effects, and the logistics of administering daily injections have been among an obstacle course of barriers to completing the previous recommended regimen for deadly drug-resistant disease that until effectively treated remains transmissable. The new regimen including bedaquiline and without the injectables is projected to last from 18 to 20 months, longer than the older regimen — when the older regimen is effective, but, WHO indicates posing fewer challenges to completion.
Examinations of data representing 12,000 patient records from 50 studies of longer regimens, new data from countries using bedaquiline, and 2017 results from a clinical delamanid trial, were among the evidence sources leading to the recommendations, according to the summary.
In its 2017 report on the global impacts of TB WHO reported that during the preceding year more than 600,000 people had become sick with tuberculosis resistant to the most effective first-line drug, and 490,000 of them had TB resistant to additional medicines as well. Still research has continued to find only about 20 percent of people needing the newer drugs have had access to them four years following WHO recommendations that the drugs be made available as a last resort when other options had failed or were unacceptable.
The Treatment Action Group, the Global TB Community Advisory Board, the TB Alliance and Médecins Sans Frontières praised the recommendations today with caveats, calling on drug makers to reduce the price of the new drugs and make them more widely accessible through country registrations, for research to develop and support the use of new medicines, and for governments to follow existing evidence and adopt the preferred treatment regimens quickly.