Shortened treatment regimens versus the standard regimen for drug‐sensitive pulmonary tuberculosis

12 Dec 2019

What was the aim of this review?

The aim of this Cochrane Review was to find out if the duration of anti‐tuberculosis treatment (ATT) for people with newly diagnosed drug‐sensitive pulmonary tuberculosis can be shortened to less than six months. Cochrane Review authors collected and analysed all relevant studies to answer this question and found five relevant studies.

Key messages

Shortened ATT regimens probably make little or no difference in death, treatment failure, or serious adverse events compared to six‐month ATT regimens, but they probably increase relapse of tuberculosis. Six large ongoing trials are studying this question.

What was studied in the review?

Tuberculosis is an infectious disease, and tuberculosis affecting the lungs (pulmonary tuberculosis) is the most common presentation of tuberculosis in adults. Tuberculosis is a major public health problem worldwide, and among infectious diseases, it is the leading cause of death.

People with pulmonary tuberculosis are currently treated with a six‐month combination of drugs that include isoniazid, rifampicin, ethambutol, and pyrazinamide for two months, followed by isoniazid and rifampicin (with or without ethambutol) for four months. Many people do not finish the treatment or they take the drugs irregularly because of the long treatment duration, or because of drug side effects. Incomplete or irregular treatment can lead to treatment failure and can increase disease relapse. Such treatment can also lead to drug resistance. If newer drug combinations given for less than six months are found to be as effective and safe as the currently recommended six‐month ATT regimens, more people might be adherent and might complete treatment. This could help reduce drug resistance and could help to stop tuberculosis infection worldwide.

What are the main results of the review?

The five included trials studied 5825 adults with newly diagnosed drug‐sensitive pulmonary tuberculosis from 14 countries with high tuberculosis transmission in Asia, Africa, and Latin Ameria. Three trials included 572 HIV‐positive people, but all excluded people with other serious comorbid conditions and those with diabetes mellitus. This reduced the applicability of study results. All were funded by government or international agencies.

Four studies replaced isoniazid or ethambutol with moxifloxacin or gatifloxacin in four‐month ATT regimens. Follow‐up was provided for 12 months to 24 months after treatment completion. In one ongoing study, moxifloxacin was added to four‐month ATT, but study authors provided only interim results.

This review shows the following when four‐month ATT regimens are compared to standard six‐month ATT regimens.

• Relapse after successful treatment is probably increased (moderate‐certainty evidence).
• Death from any cause, treatment failure, and serious adverse events are probably little or no different (moderate‐certainty evidence).
• Drug resistance may not be increased with moxifloxacin‐containing four‐month regimens (low‐certainty evidence), but we are uncertain whether this applies to gatifloxacin‐containing regimens (very low‐certainty evidence).

How up‐to‐date is this review?

The review authors searched for available studies up to 10 July 2019.