Interferons in relapsing remitting multiple sclerosis: a systematic review
Graziella Filippini, Luca Munari, Barbara Incorvaia, George C Ebers, Chris Polman, Roberto D'Amico, George P A Rice
Unità di Neuroepidemiologia, Istituto Nazionale Neurologico "C Besta", Milan, Italy (G Filippini MD); Mediss Medical Services, Milan (L Munari MD); Clinica Neurologica, Università degli Studi, Milan (B Incorvaia, MD); Clinical Neurology, University of Oxford, Radcliffe Infirmary, Oxford, UK (G C Ebers MD); Neurology VU Medical Centre, Amsterdam, Netherlands (C Polman MD); Università degli Studi di Modena e Reggio Emilia Dipartimento di Scienze Igienistiche, Microbiologiche e Biostatistiche, Modena, Italy (R D'Amico PhD); Clinical Neurological Sciences, University of Western Ontario, London, Ontario, Canada (G P A Rice MD)
Correspondence to: Dr Graziella Filippini, Unit of Neuroepidemiology, National Neurological Institute "C Besta", via Celoria 11, 20133 Milan, Italy (e-mail:gfilippini@istituto-besta.it)
Summary
Background Recombinant interferons have been approved by many national regulatory agencies for treatment of relapsing remitting multiple sclerosis, but widespread discussion continues about their true effectiveness, benefits, side-effects, and costs.
Methods With the Cochrane Collaboration methodology, we reviewed all published, randomised, placebo-controlled trials of recombinant interferons undertaken in patients with relapsing remitting multiple sclerosis between 1993 and 2002. Our primary aim was to find out whether recombinant interferons reduced the number of patients who had clinical exacerbations and disease progression, compared with placebo.
Findings The seven trials that met our criteria included 1215 randomised patients: data from 667 (55%) were available for analysis at 1 year's and from 919 (76%) at 2 years' follow-up. Interferon seemed to reduce the number of patients who had exacerbations during the first year of treatment (relative risk 0·73, 95% CI 0·54-0·99), but results at 2 years' follow-up were not robust and were difficult to interpret because of the many dropouts. Although the number of patients who had exacerbations (0·81, 0·74-0·89) or progressed (0·70, 0·55-0·88) during the first 2 years fell significantly in the protocol analysis, results were inconclusive after sensitivity analyses for exacerbations (1·11, 0·73-1·68) and disease progression (1·31, 0·60-2·89). Data were insufficient to establish whether steroid use and admissions to hospital were reduced in the interferon group. Similarly, MRI outcome data could not be analysed quantitatively. Side-effects were common, and acute toxic effects adversely affected quality of life.
Interpretation Recombinant interferons slightly reduce the number of patients who have exacerbations during first year of treatment. Their clinical effect beyond 1 year is uncertain and new trials are needed to assess their long-term effectiveness and side-effects.
Lancet 2003; 361: 545-52
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