Seven studies (three randomised trials, three retrospective cohorts, and one prospective and retrospective observational study) were included in the review. The exact number of participants was not clear, but it appeared that 1,513 patients were treated with low- or high-dose beta-interferon-1a, or high-dose beta-interferon-1b. Limitations of the included studies identified in the review were lack of randomisation (four studies), disproportionate group assignment (two studies) and disproportionate attrition (two studies). All studies were reported as either not blinded or not double blinded.
Although the authors stated that all studies provided data in a suitable format for relative risk and risk difference pooling, the forest plots showed some studies were not estimable.
Relapse status: High-dose beta-interferon-1b (RR 0.75, 95% CI 0.60 to 0.93; RD -0.12, 95% CI -0.21 to -0.03; four studies; 450 patients) and high-dose beta-interferon-1a (RR 0.88, 95% CI 0.79 to 0.98; RD -0.07, 95% CI -0.13 to -0.01; four studies; 919 patients) were associated with a lower relapse rate than low-dose beta-interferon-1a. There was no evidence of heterogeneity for beta-interferon-1b studies, but there was strong evidence of heterogeneity between studies for beta-interferon-1a. When the two high-dose treatments were combined and compared with the low-dose treatment, similar patterns for the effect on relapse were found. The two studies (n=100 patients) that compared the two high-dose treatments (beta-interferon-1a versus beta-interferon-1b) found no difference in relapse rates between the two treatment arms.
Progression-free status - Extended Disability Status Scale (EDSS) stability (two studies; 344 patients): High-dose beta-interferon-1b was associated with a lower EDSS stability than low-dose beta-interferon-1a, which approached but did not meet statistical significance (RR 0.90, 95% CI 0.79 to 1.01; RD -0.08, 95% CI -0.17 to 0.01); there was heterogeneity between studies. There was no difference in EDSS stability between interferon-beta-1a at high or low dose, and no difference between combined high-dose treatments or low-dose beta-interferon-1a (I2=54% for RR analysis; I2=57% for RD analysis).
MRI stability (two studies; 865 patients): Total combined high-dose treatments were associated with a lower relapse rate than low-dose beta-interfeon-1a (RR 0.61, 95% CI 0.53 to 0.71; RD -0.22, 95% CI -0.29 to -0.16). There was some evidence of heterogeneity between studies (I2=56% for RR analysis; I2=23% for RD analysis).
Some studies reported on adverse events. Patients treated high-dose beta-interferon had higher rates of injection-site reactions, white blood cell dyscrasias and liver function test elevations.