Computer Model Predictions Support New Multidrug-resistant TB Treatment Regimen

An alternative antibiotic treatment regimen for multidrug-resistant tuberculosis (TB) endorsed by WHO shows promising effects in a new study using computer modeling.

According to the World Health Organization (WHO), about 480,000 people around the world developed a form of multidrug-resistant tuberculosis (MDR-TB) in 2015, exacerbating an already deadly disease epidemic. Now, researchers at Johns Hopkins University have developed a new tool to predict the effectiveness of a new treatment regimen, thus, offering a look into the benefits it may have over conventional treatment.

For decades, the best treatment option for both latent TB and TB disease have included the antibiotic medications isoniazid and rifampicin, and in cases of drug-susceptible infections, the course of treatment lasts from 3 to 9 months. The Mycobacterium tuberculosis bacteria that cause these virulent lung infections have evolved since the introduction of antibiotic drugs, and thus, mutant strains of MDR-TB have emerged. These resistant strains can no longer be treated with conventional drug regimens. For those who develop such an infection, the alternative treatment plan consists of a costly combination of injectable and oral antibiotics for anywhere between 18 months to 2 years. In many cases, these MDR-TB drugs aren’t even available, according to WHO, and patients find the rigorous regimen difficult to adhere to. As a result, even more extensively drug-resistant TB (XDR-TB) and harder-to-treat strains have developed.

In a new study recently published in the journal The Lancet Respiratory Medicine, researchers at Johns Hopkins examined a new drug regimen for MDR-TB which offers a shorter course of treatment. Study authors noted that these drug-resistant infections result in more than 100,000 deaths each year, and that the recommended long-term treatment has only a 50% success rate worldwide due to issues with drug effectiveness and patient adherence. In 2016, WHO released a new set of treatment guidelines for drug-resistant TB, which recommended a regimen involving second-line drugs to be taken for a shorter period of time (just 9 to 12 months); this regimen costs each individual less than $1,000 and has cured more than 80% of patients, making it preferable in both cost, treatment duration, and effectiveness. “About 15 to 20 percent of patients who start conventional treatment for drug-resistant TB don’t finish, mostly because of the length, expense and discomfort associated with it,” said study author Emily Kendall, MD, in a recent press release. “The short-course regimen could cut both treatment time and cost of treatment in half.”

In the new study, the researchers developed a computer model to predict the epidemiological impact of the new MDR-TB regimen, simulating the use of the short-course regimen in a Southeast Asia setting. The team also investigated how the success of the new drug protocol could be affected by certain conditions, including lasting effectiveness, the emergence of additional drug resistance, as well as how the savings in cost could be applied to increase access to treatment. The computer simulation predicted that over the course of 8 years, the new regimen would cause a 23% reduction in the incidence of MDR-TB overall, higher than the 14% reduction brought on by conventional treatment. When the model was set so that the regimen affected only the effectiveness of the treatment, incidence of TB fell by 14%. Incidence fell by 11% when the regimen only affected treatment availability.

The study’s findings depended on the assumption that 10% or less of potential patients would be excluded from treatment due to additional drug resistance, and that with the new regimen more patients with MDR-TB would be treated. “Several important factors are still uncertain, but if we can keep the number of excluded patients down to around 10 percent, if treatment of the other 90 percent of patients is as successful as preliminary studies suggest and if cost savings from the shorter regimen allow more patients to be treated, then this regimen is likely to have a really big impact,” said Dr. Kendall.

WHO's recommendation for the short-course MDR-TB treatment came after preliminary studies conducted in Southeast Asia as well as in Western and Central Africa, areas hit hard by these drug-resistant infections, showed positive results. However, researchers have yet to conduct large-scale clinical trials proving the regimen’s safety and efficacy. “Our computer tool can help guide certain decisions about the short regimen,” said Dr. Kendall, “but scientists and health care workers still need to be really vigilant about gathering more data on how it’s working and for whom it is working best as we begin to use it more widely.”