Type I interferons for induction of remission in ulcerative colitis.
BACKGROUND
Interferons (IFNs) are cytokines which possess immunoregulatory properties and have been used to successfully treat a number of chronic inflammatory disorders. It has been postulated that Type I IFNs may be able to re-establish the Th1/Th2 balance in Th2 predominant diseases like ulcerative colitis.


OBJECTIVE
To systematically evaluate the efficacy and safety of type I IFN therapy for induction of remission in ulcerative colitis.


METHODS
The following electronic databases were searched: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders (IBD/FBD) Group Specialised Trial Register, and http://ClinicalTrials.gov. Reference lists of trials and review articles, as well as recent proceedings from major gastroenterology meetings were manually searched. Contact was made with pharmaceutical companies manufacturing type I IFNs.


METHODS
Randomised controlled trials of type I IFNs for induction of remission in UC were included. The study population included patients of any age with active ulcerative colitis. There were no exclusions based on type, dose or duration of IFN treatment. The primary outcome was induction of remission of ulcerative colitis. Secondary outcomes included: time to remission, mean change in disease activity index score, clinical, histological or endoscopic improvement, improvement in quality of life, and adverse events.


METHODS
Two independent investigators reviewed studies for eligibility, extracted the data and assessed study quality using Jadad's criteria. A random or fixed effects model was chosen based on an assessment of heterogeneity, and studies were weighted using the DerSimonian & Laird or the Mantel-Haenszel method accordingly. Meta-analysis was performed using RevMan 4.2.10 software.


RESULTS
Four studies were eligible for inclusion. Three studies compared type I IFNs to placebo and a single study compared IFNs to prednisolone enemas in patients with left-sided colitis. Meta-analysis was based on the three IFN-placebo studies. There was no significant benefit of type I IFNs over placebo for inducing remission in ulcerative colitis (RR 1.24; 95% CI 0.81 to 1.90). There were no statistically significant differences in any of the secondary outcome variables.


CONCLUSIONS
The existing literature does not support the efficacy of type I IFNs for induction of remission in patients with UC. Given concerns regarding the tolerability of IFN therapy, we suggest that the results of two ongoing trials are evaluated for efficacy and safety prior to development or commencement of further randomised controlled trials of type I IFNs in UC.
Seow
Cynthia H
CH
Mount Sinai Hospital, Room 445, 600 University Ave, Toronto, Ontario, Canada, M5G 1X5. cynthia.seow@utoronto.ca
Benchimol
Eric I
EI
Griffiths
Anne Marie
AM
Steinhart
A Hillary
AH
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000627:therapeutic use; D016899:Interferon-beta / Q000627:therapeutic use; D011239:Prednisolone / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012074:Remission Induction
D000893:Anti-Inflammatory Agents; D007370:Interferon Type I; D016898:Interferon-alpha; D016899:Interferon-beta; D011239:Prednisolone