Twelve parallel-group RCTs were included (n=1,445) and the sample size ranged from 42 to 257. All trials were classified as at moderate risk of bias. Three used computer-generated allocation sequencing and one described allocation concealment. All were described as double-blind, but none reported blinded assessment of the outcome. Two RCTs described losses to follow-up and used intention-to-treat analysis and seven described withdrawals, drop-outs, and losses to follow-up, but did not use intention-to-treat analysis.
Complete response rate: Locally applied interferon was associated with a statistically significant increase in complete response rate (44.4%) compared with placebo (16.1%; RR 2.68, 95% CI 1.79 to 4.02; seven trials). There was no significant difference in complete response rate between systemically administered interferon (27.4%) and placebo (26.4%; five trials).
Recurrence rate: There was no significant difference in recurrence rate between interferon (21.1%) and placebo (34.2%; seven trials). Locally applied interferon was associated with a significant reduction in recurrence rate compared with placebo (RR 0.57, 95% CI 0.38 to 0.88; four trials), but there was no significant difference between systematically administered interferon and placebo (three trials).
Significant heterogeneity (p<0.10) was found for most outcomes, except systemically administered interferon.
Adverse events: The most commonly reported adverse event was flu-like symptoms. Intralesional interferon was associated with application-site reactions. In some trials, systemically administered interferon was associated with leucopenia and thrombocytopenia. There were no significant differences between treatment and placebo groups in liver-function tests, blood urea nitrogen, and creatinine levels.