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Meta-Analysis
. 2016 Jul 22;7(7):CD000299.
doi: 10.1002/14651858.CD000299.pub3.

Anti-tuberculous therapy for maintenance of remission in Crohn's disease

Petrease H Patton  1 , Claire E Parker, John K MacDonald, Nilesh Chande
Affiliations
Meta-Analysis

Anti-tuberculous therapy for maintenance of remission in Crohn's disease

Petrease H Patton et al. Cochrane Database Syst Rev. .

Abstract

Background: There have been a number of studies with conflicting results which have examined the effect of anti-tuberculous therapy in Crohn's disease. A meta-analysis was performed to evaluate the use of anti-tuberculous therapy for the maintenance of remission in Crohn's disease.

Objectives: To evaluate the effects of anti-tuberculous therapy for the maintenance of remission in patients with Crohn's disease.

Search methods: We searched MEDLINE, EMBASE, the Cochrane LIbrary, and the Cochrane IBD Group Specialized Register from inception to June 22, 2015.

Selection criteria: Randomized controlled trials (RCTs) of anti-tuberculous therapy compared to placebo or another active therapy in patients with quiescent Crohn's disease were considered for inclusion.

Data collection and analysis: At least two authors independently extracted data and assessed the quality of included studies using the Cochrane risk of bias tool. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for dichotomous outcomes.. The primary outcome was relapse. Secondary outcomes included adverse events, withdrawals due to adverse events and serious adverse events. All data were analyzed on an intention-to-treat basis. The overall quality of the evidence supporting the primary and secondary outcomes was evaluated using the GRADE criteria.

Main results: Four placebo-controlled RCTs including 206 participants were included. Three trials included an 8 to 16 week induction phase with tapering corticosteroids (prednisone, prednisolone or methylprednisolone) as induction therapy. Anti-tuberculous therapy included monotherapy with clofazimine, combination therapy with clofazimine, rifampin, ethambutol, and dapsone or combination therapy with clarithromycin, rifabutin and clofazimine. All of the studies were rated as unclear risk of bias for allocation concealment, three were rated as unclear risk of bias for random sequence generation and two were rated as unclear risk of bias for blinding or participants and personnel. There was a statistically significant difference in relapse rates favoring anti-tuberculous therapy over placebo. Thirty-nine per cent (44/112) of patients in the anti-tuberculous therapy group relapsed at 9 months to 2 years compared to 67% (63/94) of placebo patients (RR 0.58, 95% CI 0.45 to 0.75, I(2) = 47%). A GRADE analysis indicates that the overall quality of the evidence supporting this outcome was very low due to unknown risk of bias and sparse data. Adverse events occurred more frequently in the anti-tuberculous therapy group (37/159) compared to the placebo group (14/163) with a pooled RR of 2.57 (95% CI 1.45 to 4.55; N=322; studies=4, I(2)=64%). A GRADE analysis indicates that the overall quality of the evidence supporting this outcome was very low due to unknown risk of bias, unexplained heterogeneity and sparse data. There was no difference in withdrawals due to adverse events. Nine per cent (14/159) of anti-tuberculous therapy patients withdrew due to adverse events compared to 7% (11/163) of placebo patients (RR 1.29, 95% CI 0.60 to 2.77, I(2) = 0%). Common adverse events included increased skin pigmentation and rashes. No serious adverse events were reported in any of the included studies.

Authors' conclusions: Anti-tuberculous therapy may provide a benefit over placebo for the prevention of relapse in participants with Crohn's disease in remission. However, this result is very uncertain due to unclear study quality and the small numbers of patients assessed. Further studies are needed to provide better quality evidence for the use of anti-tuberculous therapy for maintaining remission in people with quiescent Crohn's disease.

PubMed Disclaimer

Conflict of interest statement

Petrease H Patton: None known.

Claire E Parker: None known.

John K MacDonald: None known.

Nilesh Chande has received funds from AbbVie, Ferring, and Actavis for consulting; payment for lectures from Abbvie; payment for development of educational presentations from AbbVie; has stock or stock options in Pfizer, Glaxo Smith Kline, Procter and Gamble, and Johnson and Johnson; and has received travel support from Merck. All of these activities are outside the submitted work.

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Anti‐TB therapy versus placebo, Outcome 1 Relapse.
1.2
1.2. Analysis
Comparison 1 Anti‐TB therapy versus placebo, Outcome 2 Adverse events.
1.3
1.3. Analysis
Comparison 1 Anti‐TB therapy versus placebo, Outcome 3 Withdrawals due to adverse events.
1.4
1.4. Analysis
Comparison 1 Anti‐TB therapy versus placebo, Outcome 4 Serious adverse events.
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