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Review
, 11 (11), CD012163

Six-month Therapy for Abdominal Tuberculosis

Affiliations
Review

Six-month Therapy for Abdominal Tuberculosis

Sophie Jullien et al. Cochrane Database Syst Rev.

Abstract

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 methods: 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).

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.

Conflict of interest statement

SJu and HR are employed by the CIDG, which is funded by a grant from the Department for International Development (DFID), UK. SJa has no known conflicts of interest. VA is an author of one of the included trials, Makharia 2015a; he was not involved in the data extraction and the 'Risk of bias' assessment of this study.

Figures

Figure 1
Figure 1
Study flow diagram.
Figure 2
Figure 2
'Risk of bias' summary: review authors' judgements about each 'Risk of bias' item for each included trial.
Figure 3
Figure 3
'Summary of findings' table.
Figure 4
Figure 4
Forest plot of comparison: 2 Six‐month ATT versus nine‐month ATT, outcome: 2.2 Clinical cure.
Analysis 1.1
Analysis 1.1
Comparison 1 Six‐month versus nine‐month ATT, Outcome 1 Relapse.
Analysis 1.2
Analysis 1.2
Comparison 1 Six‐month versus nine‐month ATT, Outcome 2 Clinical cure.
Analysis 1.3
Analysis 1.3
Comparison 1 Six‐month versus nine‐month ATT, Outcome 3 Complete healing of active lesions, documented by endoscopy or histopathology.
Analysis 1.4
Analysis 1.4
Comparison 1 Six‐month versus nine‐month ATT, Outcome 4 Death from any cause.
Analysis 1.5
Analysis 1.5
Comparison 1 Six‐month versus nine‐month ATT, Outcome 5 Treatment failure.
Analysis 1.6
Analysis 1.6
Comparison 1 Six‐month versus nine‐month ATT, Outcome 6 Default.
Analysis 1.7
Analysis 1.7
Comparison 1 Six‐month versus nine‐month ATT, Outcome 7 Participants with AE that lead to the discontinuation or modification of ATT.
Analysis 1.8
Analysis 1.8
Comparison 1 Six‐month versus nine‐month ATT, Outcome 8 Participants with other AE relating to ATT.
Analysis 2.1
Analysis 2.1
Comparison 2 Sensitivity analyses, Outcome 1 Relapse.
Analysis 2.2
Analysis 2.2
Comparison 2 Sensitivity analyses, Outcome 2 Clinical cure.

Update of

  • Cochrane Database Syst Rev. doi: 10.1002/14651858.CD012163

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References

References to studies included in this review

    1. Makharia GK, Ghoshal UC, Ramakrishna BS, Agnihotri A, Ahuja V, Chowdhury SD, et al. Intermittent directly observed therapy for abdominal tuberculosis: a multicenter randomized controlled trial comparing 6 months versus 9 months of therapy. Clinical Infectious Diseases 2015;61(5):750‐7. [DOI: 10.1093/cid/civ376] - DOI - PubMed
    1. Park SH, Yang SK, Yang DH, Kim KJ, Yoon SM, Choe JW, et al. Prospective randomized trial of six‐month versus nine‐month therapy for intestinal tuberculosis. Antimicrobial Agents and Chemotherapy 2009;53(10):4167‐71. - PMC - PubMed
    1. Tony J, Sunilkumar K, Thomas V. Randomized controlled trial of DOTS versus conventional regime for treatment of ileocecal and colonic tuberculosis. Indian Journal of Gastroenterology 2008;27(1):19‐21. - PubMed

References to studies excluded from this review

    1. Balasubramanian R, Nagarajan M, Balambal R, Tripathy SP, Sundararaman R, Venkatesan P, et al. Randomised controlled clinical trial of short course chemotherapy in abdominal tuberculosis: a five‐year report. International Journal of Tuberculosis and Lung Disease 1997;1(1):44‐51. - PubMed
    1. Makharia GK, Agnihotri A, Chaudhary S, Ghoshal U, Pathak MK, Mishra A, et al. A comparison of efficacy of 6 months and 9 months of intermittent anti‐tuberculous therapy for abdominal tuberculosis (intestinal and peritoneal): a randomized controlled trial. Asian Pacific Digestive Week Conference, 2014 Nov 22‐25; Bali, Indonesia. Journal of Gastroenterology and Hepatology (Australia) 2014;29:238.
    1. Makharia GK, Agnihotri A, Ghoshal UC, Ramakrishna BS, Chaudhary S, Pathak MK, et al. A comparison between efficacy of 6 months and 9 months of intermittent anti‐tuberculous therapy for abdominal tuberculosis (intestinal and peritoneal): A randomized controlled trial. 55th Annual Conference of the Indian Society of Gastroenterology, ISGCON ‐ 2014, 2014 Dec 19‐23; Mumbai. Indian Journal of Gastroenterology 2014;33(1 Suppl 1):A18.
    1. Makharia GK, Ghoshal UC, Ramakrishna BS, Agnihotri A, Ahuja V, Chowdhury SD, et al. Intermittent supervised therapy for abdominal tuberculosis: a multicenter randomized controlled trial comparing 6 months versus 9 months duration of therapy. Version civ376v1. http://cid.oxfordjournals.org/content/early/2015/05/11/cid.civ376 (accessed 7 September 2016). [DOI: 10.1093/cid/civ376] - DOI - PubMed

Additional references

    1. American Thoracic Society, Centers for Disease Control and Prevention, Infectious Diseases Society of America. Treatment of tuberculosis. Morbidity and Mortality Weekly Report 2003;52(RR‐11):1‐77. - PubMed
    1. Bolukbas C, Bolukbas FF, Kendir T, Dalay RA, Akbayir N, Sokmen MH, et al. Clinical presentation of abdominal tuberculosis in HIV seronegative adults. BMC Gastroenterology 2005;5:21. - PMC - PubMed
    1. Debi U, Ravisankar V, Prasad KK, Sinha SK, Sharma AK. Abdominal tuberculosis of the gastrointestinal tract: revisited. World Journal of Gastroenterology 2014;20(40):14831‐40. - PMC - PubMed
    1. Golden MP, Vikram HR. Extrapulmonary tuberculosis: an overview. American Family Physician 2005;72(9):1761‐8. - PubMed
    1. GRADE Working Group, McMaster University. GRADEpro GDT. Version accessed 06 September 2016. Hamilton (ON): GRADE Working Group, McMaster University, 2014.

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