Abstract
Background
Therapy with either recombinant beta-1a or beta-1b interferons (IFNs) is worldwide approved for Relapsing Remitting Multiple Sclerosis (RRMS). A major unanswered question is whether this treatment is able to safely reverse or retard the progressive phase of the disease.
Objectives
The main objective was to verify whether IFNs treatment in Secondary Progressive Multiple Sclerosis (SPMS) is more effective than placebo in reducing the number of patients who experience disability progression.
Search methods
We searched the Cochrane Multiple Sclerosis Group’s Trials Register (1995 to 15 February 2011), the reference lists of relevant articles and conference proceedings. Regulatory agencies were used as additional sources of information.
Selection criteria
We included all randomised, double or single blind, placebo-controlled trials (RCTs) evaluating the efficacy of IFNs versus placebo in SPMS patients.
Data collection and analysis
Two review authors independently assessed all reports retrieved from the search. They independently extracted clinical, safety and MRI data, using a predefined data extraction form, resolving disagreements after discussion with a third reviewer. Risk of bias was evaluated to assess the quality of the studies. Treatment effect was measured using Risk Ratio (RR) with 95% confidence intervals (CI) for the binary outcomes and Standard Mean Difference with 95% CI for the continuous outcomes.
Main results
Five RCTs met the inclusion criteria, from which 3122 (1829 IFN and 1293 placebo) treated patients contributed to the analysis. Included population was heterogeneous in terms of baseline clinical characteristics of the disease, in particular the percentage of patients affected by secondary progression with superimposed relapse ranging from 72% to 44%. IFN beta 1a and 1b did not decrease the risk of progression sustained at 6 months (RR, 95% CI: 0.98, [0.82-1.16]) after three years of treatment. A significant decrease of the risk of progression sustained at 3 months (RR, 95% CI: 0.88 [0.80, 0.97]) and of the risk of developing new relapses at three years (RR 0.91, [0.84-0.97]) were found. The risk of developing new active brain lesions decreased over time but this data was obtained from single studies on Magnetic Resonance Imaging (MRI), performed in subgroups of patients; in spite of no effect on progression, the radiological data supported an effect on MRI parameters. The safety profile reflects what is commonly reported in MS IFN-treated patients.
Authors’ conclusions
Well designed RCTs, evaluating a high number of patients were included in the review. Recombinant IFN beta does not prevent the development of permanent physical disability in SPMS. We were unable to verify the effect on cognitive function for the lack of comparable data. This treatment significantly reduces the risk of relapse and of short -term relapse-related disability.
Overall, these results show that IFNs’ anti-inflammatory effect is unable to retard progression, when established. In the future, no new RCTs for IFNs versus placebo in SPMS will probably be undertaken, because research is now focusing on innovative drugs. We believe that this review gives conclusive evidence on the clinical efficacy of IFNs versus placebo in SPMS.
Plain language summary
Interferon beta for Secondary Progressive Multiple Sclerosis
Interferon beta, an anti-inflammatory therapy for patients with Relapsing Remitting Multiple Sclerosis(RRMS), is also used for patients with the secondary progressive type.
Although it remains unclear how either beta-1a or beta-1b interferons (IFNs) work in MS, these therapies have been well established in RRMS. Currently, IFNs’ therapies are also the first line treatment for Secondary Progressive Multiple Sclerosis (SPMS), since other drugs, such as mitoxantrone, have a worse risk/benefit profile. A major unanswered question is whether and to what extent IFNs are really effective in SPMS.
The main objective of this review was to verify whether IFNs in patients with SPMS are more effective than placebo in reducing the number of patients who experience disability progression during the 2-3 years follow-up.
Among the pertinent literature, only five studies met the criteria of the inclusion in the review, comprising a total of 3122 participants (1829 treated with IFN and 1293 with placebo).
Overall, these results show that IFNs are unable to retard the progression once it is established, making INFs not useful in the secondary progressive phase of the disease.
The well known adverse events related to IFNs’ treatment such as injection site reactions, influenza like syndrome, and leukopenia occurred frequently also in SPMS patients, while serious and life-threatening adverse events were not increased in the treated group of patients.
Because this review has considered well designed studies with a high number of patients, the authors believe that its results give conclusive evidence on the clinical efficacy of IFN beta versus placebo in patients with SPMS. Research focused on innovative drugs is mandatory.
