Background: This is an updated Cochrane review of the previous version published (Cochrane Database of Systematic Reviews 2009, Issue 1. Art. No.: CD006643. DOI: 10.1002/14651858.CD006643.pub2).Therapeutic trials with ss-interferon in Multiple Sclerosis (MS) have mainly focused on remitting-relapsing multiple sclerosis (RRMS), demonstrating a reduction in relapse rate. However, there is not enough evidence about their efficacy in patients with primary progressive multiple sclerosis (PPMS).

Objectives: Identify and summarize the evidence that ss-interferon is beneficial and safe in patients with PPMS.

Search strategy: We searched the Cochrane MS Group Trials Register (May 2009); The Cochrane Central Register of Controlled Trials (CENTRAL) The Cochrane Library, (2009, Issue 2); MEDLINE (PubMed) (January 1966 to May 2009), EMBASE (January 1974 to May 2009); NICE (January 1999 to May 2009); LILACS (January 1986 to May 2009); Screening of reference lists of all primary studies found; Contact and inquiry of drug manufactures and multiple sclerosis experts.

Selection criteria: Randomized double or single blind, placebo-controlled trials of recombinant ss-interferon in patients with PPMS including trials of MS which report separate outcomes in subgroups of patients with PPMS.

Data collection and analysis: Two reviewers independently extracted and assessed trials' quality according to the criteria outlined in The Cochrane Handbook.

Main results: Of 1777 potential studies evaluated, only two Randomized Control Trials (123 patients) were included. ss-interferon treatment compared to placebo did not show differences regarding the proportion of patients with progression of the disease (RR 0.89, 95% CI 0.55 to1.43), and it was associated with a greater frequency of treatment-related adverse events (RR 1.90, 95% CI 1.45-2.48). One of the trials evaluated the MRI secondary outcome pre-specified in the protocol. This trial showed that at two years the numbers of active lesions on brain MRI scan in ss-interferon arm were significantly lower than in placebo arm (weighted mean difference -1.3, 95% CI -2.15 to -0.45, P = 0.003); also, the number of participants with active lesions was significantly higher in placebo arm vs. ss-interferon arm at two years (RR 0.43, 95% CI 0.22 to 0.86, P = 0.02).

Authors' conclusions: Limited data on the effect of ss-interferon treatment on PPMS exists. Only two single-centre placebo controlled trials of interferon beta have been done. Based on this review, the included studies showed that ss-interferon treatment was not associated with reduced disability progression in PPMS patients. However, the trial population was too small to allow definitive conclusions on the efficacy of ss-interferon therapy in PPMS patients. Larger research studies need to be done in patients with PPMS in order to clarify whether ss-interferon is effective in this population.