Abstract
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 methods
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.
Plain language summary
Treatments of patients with Primary Progressive Multiple Sclerosis (PPMS) with interferon beta (INF beta) seems not associated with a reduction of the disability progression
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).
Treatments of patients with Primary Progressive Multiple Sclerosis ( PPMS) with interferon beta ( INF beta) seems not associated with a reduction of the disability progression
To date there is no proven or licensed disease-modifying treatments to slow the progression of PPMS. Studies on the effects of INF beta have mainly focused on Relapsing-Remitting MS and have demonstrated a modest reduction on the progression of the disease. The objective of this review was to assess the efficacy of INF beta in patients with PPMS.
Among the pertinent medical literature only two studies, comprising a total of 123 participants, met the criteria of the methodological quality necessary for their inclusion in this review. Taking into account the disability progression, the analysis of the data showed that INF beta treatment in patients with PPMS was not associated with a reduction of this parameter during the first two years of therapy. Adverse effects, mainly flu-like symptoms and injection site reactions, occurred frequently and were the same as reported by the many studies on IFN beta treatments in MS patients with different types of the disease.
It is worth nothing that the patients’ population analysed was too small to allow a definitive conclusion on the efficacy of IFN beta therapy in PPMS.
