Drug Resistant Tuberculosis: New Study Offers New Hope

By Andrew Nunn, UCL and I.D. Rusen, University of Toronto

Tuberculosis is the leading cause of death in the world due to a single infectious disease, causing more deaths than HIV / AIDS. In 2017, 10 million people became infected with tuberculosis worldwide and about 1.6 million died.

One of the main obstacles to the fight against the epidemic is the growing resistance to drugs that cure tuberculosis.

The World Health Organization (WHO) has declared that drug-resistant TB is a global health crisis. In 2017, around 558,000 people worldwide have developed the most effective first-line drug-resistant tuberculosis – rifampicin (RR-TB). Of these, 82% had multidrug-resistant tuberculosis.

However, the treatment of drug-resistant TB remains desperately ineffective. The 20 to 24 month regimen used in many countries to treat patients is expensive and has significant side effects. In addition, the length of treatment prevents patients from adhering, just like health systems, to maintaining. Globally, treatment has an average success rate of just over 50% in real – world treatment facilities, although there is considerable variation in treatment. one country to another.

As a result, researchers around the world are urgently exploring shorter, more effective and safer treatments for patients with drug-resistant TB.

One of these efforts has begun to bear fruit. The results of phase 1 of a clinical trial have recently been published. The news is encouraging. The trial demonstrates that a shorter treatment, nine to eleven months, is as effective for the treatment of multidrug-resistant tuberculosis as the twenty-month-long longer treatment recommended by WHO in 2011.

The STREAM trial provides strong evidence for the efficacy and safety of 9 to 11 months of treatment compared to a much longer 20-month treatment. The results are also good and the fact that the treatment regimen is shorter should make it much more acceptable to patients. This should also result in cost savings for patients and health services.

The trial

STREAM (Standardized Therapeutic Drug Plan for MDR-TB Patients) is the world's first multi-country randomized phase III clinical trial to test the efficacy, safety and economic impact of treatment regimens shortcuts. The randomized nature of the test means that patients have been badigned to the long or short treatment regimen so as to avoid bias. The allocation of treatment is determined by chance and not by the choice of a doctor.

Phase III trials are designed to evaluate the effectiveness and safety of a new intervention in practice.

Phase 1 of the trial aimed to determine whether a nine-to-eleven-month regimen with promising cure rates during a pilot program in Bangladesh was as effective as the longer treatment regimen evaluated in other settings in Bangladesh. rigorous controlled test conditions. Seven sites in Vietnam, Mongolia, South Africa and Ethiopia participated.

The results of phase 1 show that the shortest regimen is as effective as the 20-month regimen.

Nearly 80% of patients participating in the trial had a favorable outcome after two and a half years of follow-up from the start of the trial. The percentage was 79.8% in the 20-month plan. In the nine to eleven-month regimen, the percentage was 78.8%.

The results for HIV-positive participants, although not as good as those who were HIV-negative, were very similar in the short and long-term regimen.

The conclusions about side effects were also interesting. The rates of serious side effects observed during treatment and follow-up between the two regimens were very similar. But there were differences in the types of side effects. The most common adverse effects were cardiac conduction disorders, which increase the risk of serious and potentially fatal arrhythmias, during the nine to eleven month regimen. In the 20-month regimen, the most common adverse events were metabolic disorders, particularly hypokalemia.

An badysis of economic health data is underway and will evaluate the potential savings for patients and health systems when the nine-month-to-eleven-month diet is compared to the twenty-month diet.

conclusions

The final results of the trial are encouraging because they show that the efficacy and safety of the nine-to-11-month regimen are comparable to those of a 20-month regimen. This encourages the use of a shorter treatment regimen for patients with rifampicin-resistant TB.

The nine to eleven month treatment regimen has substantial benefits. It reduces treatment times, can improve patient retention under programmatic conditions, and reduces the number of pills patients need to take.

However, the required ECG monitoring is an important consideration.

In its latest guidelines published last year, the WHO again emphasized the need to continue to seek not only shorter, but also less toxic therapeutic regimens for the patient. STREAM's Stage 1 results suggest that progress is being made.

STREAM Stage 2 is currently evaluating a fully oral regimen that is potentially as effective and more tolerable as the injectable regimens currently used in some countries. This would also be another major breakthrough in the fight against multidrug-resistant TB.

Andrew Nunn, Senior Scientist, CRM Clinical Trials Unit at UCL, UCL and I.D. Rusen, Adjunct Professor, Dalla Lana School of Public Health, University of Toronto

This article is republished from The Conversation under a Creative Commons license. Read the original article.