What is ulcerative colitis?
Ulcerative colitis (UC) is a long-term (chronic) inflammatory bowel disease characterized by abdominal pain, bloody diarrhea, and a need to hurry to the toilet to pass feces (fecal urgency).
What are type I interferons?
Interferons (IFNs) are drugs that regulate the immune system and have been used to successfully treat a number of chronic inflammatory disorders. People with UC who are experiencing disease symptoms have ‘active’ disease, periods when the symptoms stop are called ‘remission’.
What did the researchers investigate?
The researchers investigated whether type I IFNs results in remission in people with active ulcerative colitis, and whether it causes any harms (side effects). The researchers searched the medical literature extensively up to August 8, 2014.
What did the researchers find?
The researchers identified six studies that included a total of 517 participants. Five studies (total 485 participants) compared type I IFNs to placebo (fake medicine) injections. One small (32 participants) low quality study compared types I IFNs to prednisolone (a steroid drug) enemas. This study did not measure remission and found no difference between the treatment groups in quality of life or disease activity scores. There was no difference between type I interferons and placebo treatment groups for the number of people who achieved remission or improvement of their symptoms. These results suggest that type I IFNs do not produce remission from ulcerative colitis. Common side effects included headaches, arthralgias (joint pain), myalgias (muscle pain), fatigue, back pain, nausea, injection site reactions, rigors (cold and shivering), and fevers.
At present, the results from medical trials do not support the use of type I IFNs for the production of remission in active ulcerative colitis.
Moderate quality evidence suggests that type I IFNs are not effective for the induction of remission in UC. In addition, there are concerns regarding the tolerability of this class of treatment.
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.
To systematically evaluate the efficacy and safety of type I IFN therapy for induction of remission in ulcerative colitis.
We searched MEDLINE, EMBASE, CENTRAL, the Cochrane IBD/FBD group specialised register, and ClinicalTrials.gov from inception to August 8, 2014. Reference lists of trials and review articles, as well as recent proceedings from major gastroenterology meetings were manually searched.
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.
Two independent authors reviewed studies for eligibility, extracted the data and assessed study quality using the Cochrane risk of bias tool. The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. 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. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for dichotomous outcomes. We calculated the mean difference and corresponding 95% confidence interval for continuous outcomes. Meta-analysis was performed using RevMan 5.3.5 software.
Six studies were eligible for inclusion (517 patients). Five studies compared type I IFNs to placebo injections (485 patients) and a single study compared IFNs to prednisolone enemas in patients with left-sided colitis (32 patients). The active comparator study was rated as high risk of bias due to an open-label design. Three studies were rated as unclear risk of bias for random sequence generation and allocation concealment. Two studies described as double blind were rated as unclear risk of bias for blinding. There was no significant benefit of type I IFNs over placebo for inducing clinical remission or improvement in patients with active ulcerative colitis. Thirty-six per cent (87/242) of patients in the type I IFNs group achieved clinical remission by 8 to 12 weeks compared to 30% (36/120) of placebo patients (RR 1.16, 95% CI 0.84 to 1.58; 4 studies, 362 patients). A GRADE analysis indicated that the overall quality of the evidence supporting the outcome clinical remission was moderate due to sparse data (123 events). Fifty-six per cent (149/264) of patients in the type I IFNs group improved clinically by 8 to 12 weeks compared to 48% (77/161) of placebo patients (RR 1.16, 95% CI 0.96 to 1.40; 4 studies, 425 patients). A GRADE analysis indicated that the overall quality of the evidence supporting the outcome clinical improvement was moderate due to sparse data (226 events). Patients who received type I IFNs were significantly more likely to withdraw from the studies due to adverse events than those who received placebo. Seven per cent (18/42) of type I IFNs patients withdrew due to adverse events compared to 2% (3/152) of placebo patients (RR 3.16, 95% CI 1.06 to 9.40). A GRADE analysis indicated that the overall quality of the evidence supporting the outcome withdrawal due to adverse events was low due to very sparse data (21 events). The study comparing type I IFNs to prednisolone enemas found no difference between the treatment groups in quality of life or disease activity scores. Common adverse events included headaches, arthralgias, myalgias, fatigue, back pain, nausea, application site reactions, rigors, and fevers. There were no statistically significant differences in the other secondary outcomes.