title: Anti-tuberculous therapy for maintenance of remission in Crohn's disease.
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.
  
  
  OBJECTIVE
  To evaluate the effects of anti-tuberculous therapy for the maintenance of remission in patients with Crohn's disease.
  
  
  METHODS
  We searched MEDLINE, EMBASE, the Cochrane LIbrary, and the Cochrane IBD Group Specialized Register from inception to June 22, 2015.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  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.
  
  
  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.
authors.affiliation: Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada.
authors.forename: Petrease H
authors.initials: PH
authors.lastname: Patton
authors.forename: Claire E
authors.initials: CE
authors.lastname: Parker
authors.forename: John K
authors.initials: JK
authors.lastname: MacDonald
authors.forename: Nilesh
authors.initials: N
authors.lastname: Chande
mesh_terms: D000995:Antitubercular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017291:Clarithromycin / Q000627:therapeutic use; D002991:Clofazimine / Q000627:therapeutic use; D003424:Crohn Disease / Q000188:drug therapy / Q000517:prevention & control*; D004977:Ethambutol / Q000627:therapeutic use; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D060046:Maintenance Chemotherapy / Q000379:methods*; D008775:Methylprednisolone / Q000627:therapeutic use; D011241:Prednisone / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D012074:Remission Induction; D017828:Rifabutin / Q000627:therapeutic use; D012293:Rifampin / Q000627:therapeutic use; D055502:Secondary Prevention
chemical_list: D000995:Antitubercular Agents; D005938:Glucocorticoids; D017828:Rifabutin; D004977:Ethambutol; D002991:Clofazimine; D017291:Clarithromycin; D011241:Prednisone; D012293:Rifampin; D008775:Methylprednisolone