Tuberculous bacteria have been suggested as a possible cause of Crohn's disease due to a similarity between Crohn's and tuberculous lesions when viewed under a microscope. Four studies examined the use of anti-tuberculous therapy to reduce the chance of the disease recurring in patients with non-active Crohn's disease. The results of these studies suggest that this treatment might be effective for this purpose. However, this finding has not been definitively proven, and anti-tuberculous therapy should not be used to treat Crohn's disease without further study.
What is Crohn's disease?
Crohn's disease is a chronic inflammatory disorder that can occur in any part of the gastrointestinal tract and can affect people of any age. Common symptoms include weight loss, diarrhoea and abdominal pain. When people with Crohn's disease experience these symptoms the disease is active. When patients no longer experience disease symptoms their disease is said to be in remission.
Review question
Prevention of relapse (recurrence of symptoms) is an important objective in the management of Crohn's disease. There is no current treatment available that completely prevents relapse and is without significant side-effects. Tuberculous bacteria have been suggested as a possible cause of Crohn's disease due to a similarity between Crohn's and tuberculous lesions when viewed under a microscope. We wanted to see if anti-tuberculous therapy is better than placebo for maintaining remission in patients with Crohn's disease
What is anti-tuberculous therapy?
Anti-tuberculous therapy generally consists of combinations of antibiotic and antibacterial type drugs.
What did the researchers investigate?
The researchers studied whether anti-tuberculous therapy maintains remission in patients with Crohn's disease and whether it causes any harms (side effects). The investigators searched the medical literature extensively up to 22 June 2015.
What did the researchers find?
The researchers identified four studies that included a total of 206 participants. All of the studies were small in size and were judged to be of unclear quality. The studies compared anti-tuberculous therapy (i.e. clofazimine or combination therapy with clofazimine, rifampin, ethambutol, and dapsone or combination therapy with clarithromycin, rifabutin and clofazimine) to placebo (inactive pills or tablets). 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. Participants receiving anti-tuberculous drugs had more side effects than placebo participants. Common side effects included reversible pink skin discolouration and rash. No serious side effects were reported in the four studies. Further studies are needed to provide better quality evidence for the use of anti-tuberculous therapy for maintaining remission in people with inactive Crohn's disease.
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.
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.
To evaluate the effects of anti-tuberculous therapy for the maintenance of remission in patients with Crohn's disease.
We searched MEDLINE, EMBASE, the Cochrane LIbrary, and the Cochrane IBD Group Specialized Register from inception to June 22, 2015.
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.
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.
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, I2 = 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, I2=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, I2 = 0%). Common adverse events included increased skin pigmentation and rashes. No serious adverse events were reported in any of the included studies.