Interferon beta for secondary progressive multiple sclerosis.
Author(s): La Mantia L, Vacchi L, Di Pietrantonj C, Ebers G, Rovaris M, Fredrikson S,
Filippini G.
Affiliation(s): Unit of Neurology - Multiple Sclerosis Center, I.R.C.C.S. Santa Maria Nascente
FondazioneDon Gnocchi, Via Capecelatro 66, Milano, 20148, Italy.
lamantialore@gmail.com.
Publication date & source: 2012, Cochrane Database Syst Rev. , 1:CD005181
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.
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