Six-month therapy for people with abdominal tuberculosis

What is abdominal tuberculosis and why is duration of treatment important?

Abdominal tuberculosis (TB) is a type of TB that affects the gut, the peritoneum (the lining of the abdominal cavity), abdominal lymph nodes, and, more rarely, the solid organs in the abdomen (liver, pancreas, and spleen). Abdominal TB leads to severe illness in adults and children, and can cause complications, such as bowel rupture, which can lead to death.

Most current guidelines recommend treating people that have abdominal TB with antituberculous treatment (ATT) for six months, but some clinicians treat for longer periods due to concerns that six months is not adequate to achieve cure and prevent relapse of the disease after the end of treatment. Longer ATT regimens have disadvantages: patients may find it more difficult to adhere to the tablets; patients are exposed to the risk of side effects of ATT for longer periods; and the cost to health systems and to patients is greater.

What the evidence shows

Cochrane researchers examined the available evidence up to the 2 September 2016. We included three trials with 328 participants that compared six-month ATT with nine-month ATT; two were from India and one was from South Korea. The trials were mostly of high quality, although two had concerns of risk of bias for detecting relapse of the disease. All the trials included HIV-negative adults with TB of the gut (gastrointestinal TB), and one also included TB of the peritoneum (peritoneal TB).

The results show that relapse was an uncommon event, but we are uncertain whether or not there is a difference between the six-month and nine-month groups as numbers of participants are small (very low quality evidence). Six-month and nine-month regimens are probably similarly effective in terms of the chances of achieving cure (moderate quality evidence). Death was uncommon in both groups, and all deaths occurred during the first four months of ATT, which suggests that duration of treatment did not have an effect on risk of death. Few people had poor treatment compliance, and few participants experienced side effects that led to their treatment being stopped or changed, and it was not possible to detect a difference between the groups.

Six-month regimens are probably as good as nine-month regimens in terms of numbers of people cured. We found no evidence to suggest that six-month regimens are less safe for gastrointestinal and peritoneal TB than nine-month regimens, but we still do not know whether there is a difference in risk of relapse between the two regimens. Further studies are needed to increase our confidence as to whether six-month regimens are as good as nine-month regimens for preventing relapse; and to provide information about treating abdominal TB in children and in people with HIV.

Authors' conclusions: 

We found no evidence to suggest that six-month treatment regimens are inadequate for treating people that have intestinal and peritoneal TB, but numbers are small. We did not find any incremental benefits of nine-month regimens regarding relapse at the end of follow-up, or clinical cure at the end of therapy, but our confidence in the relapse estimate is very low because of size of the trials. Further research is required to make confident conclusions regarding the safety of six-month treatment for people with abdominal TB. Larger studies that include HIV-positive people, with long follow-up for detecting relapse with reliability, would help improve our knowledge around this therapeutic question.

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Background: 

Tuberculosis (TB) of the gastrointestinal tract and any other organ within the abdominal cavity is abdominal TB, and most guidelines recommend the same six-month regimen used for pulmonary TB for people with this diagnosis. However, some physicians are concerned whether a six-month treatment regimen is long enough to prevent relapse of the disease, particularly in people with gastrointestinal TB, which may sometimes cause antituberculous drugs to be poorly absorbed. On the other hand, longer regimens are associated with poor adherence, which could increase relapse, contribute to drug resistance developing, and increase costs to patients and health providers.

Objectives: 

To compare six-month versus longer drug regimens to treat people that have abdominal TB.

Search strategy: 

We searched the following electronic databases up to 2 September 2016: the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase (accessed via OvidSP), LILACS, INDMED, and the South Asian Database of Controlled Clinical Trials. We searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for ongoing trials. We also checked article reference lists.

Selection criteria: 

We included randomized controlled trials (RCTs) that compared six-month regimens versus longer regimens that consisted of isoniazid, rifampicin, pyrazinamide, and ethambutol to treat adults and children that had abdominal TB. The primary outcomes were relapse, with a minimum of six-month follow-up after completion of antituberculous treatment (ATT), and clinical cure at the end of ATT.

Data collection and analysis: 

Two review authors independently selected trials, extracted data, and assessed the risk of bias in the included trials. For analysis of dichotomous outcomes, we used risk ratios (RR) with 95% confidence intervals (CIs). Where appropriate, we pooled data from the included trials in meta-analyses. We assessed the quality of the evidence using the GRADE approach.

Main results: 

We included three RCTs, with 328 participants, that compared six-month regimens with nine-month regimens to treat adults with intestinal and peritoneal TB. All trials were conducted in Asia, and excluded people with HIV, those with co-morbidities and those who had received ATT in the previous five years. Antituberculous regimens were based on isoniazid, rifampicin, pyrazinamide, and ethambutol, and these drugs were administered daily or thrice weekly under a directly observed therapy programme. The median duration of follow-up after completion of treatment was between 12 and 39 months.

Relapse was uncommon, with two cases among 140 participants treated for six months, and no events among 129 participants treated for nine months. The small number of participants means we do not know whether or not there is a difference in risk of relapse between the two regimens (very low quality evidence). At the end of therapy, there was probably no difference in the proportion of participants that achieved clinical cure between six-month and nine-month regimens (RR 1.02, 95% CI 0.97 to 1.08; 294 participants, 3 trials, moderate quality evidence). For death, there were 2/150 (1.3%) in the six-month group and 4/144 (2.8%) in the nine-month group. All deaths occurred in the first four months of treatment, so was not linked to the duration of treatment in the included trials. Similarly, the number of participants that defaulted from treatment was small in both groups, and there may be no difference between them (RR 0.50, 95% CI 0.10 to 2.59; 294 participants, 3 trials, low quality evidence). Only one trial reported on adherence to treatment, with only one participant allocated to the nine-month regimen presenting poor adherence to treatment. We do not know whether six-month regimens are associated with fewer people experiencing adverse events that lead to treatment interruption (RR 0.53, 95% CI 0.18 to 1.55; 318 participants, 3 trials, very low quality evidence).

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