A Cochrane review included 8 studies with a total of 1 563 subjects. The drug was interferon-alpha (IFN) alfa-2b in 6 studies and alfa-2a in two. The studies were heterogeneous in terms of diagnosis of follicular lymphoma (FL), using several classification systems. IFN was compared with placebo/no intervention in 5 studies and other chemotherapy in three. The effect of IFN was similar to that of placebo on overall survival (HR 0.90, 95% CI 0.61 to 1.34, statistical heterogeneity, I2 = 63%; 5 studies, n=1 100) whereas IFN was more effective when added to chemotherapy (HR 0.68, 95% CI 0.52 to 0.90; 3 studies, n=463). Considering IFN versus all comparators, IFN was effective in prolonging progression-free survival (HR 0.66, 95% CI 0.57 to 0.77; 6 studies, n=1 357) and overall survival (fixed effects HR 0.79, 95% CI 0.67 to 0.94, I2 = 52%; 8 studies, n=1 563). After adjustment for heterogeneity this statistically significance disappeared (random effects HR 0.82, 95% CI 0.63 to 1.08). Toxicity and patients lost to follow up were significantly higher in the IFN groups.
Comment: The quality of evidence is downgraded by study quality (unclear allocation concealment) and by inconsistency (heterogeneity in interventions).