Efficacy of intramuscular interferon beta-1a in patients with clinically isolated syndrome: analysis of subgroups based on new risk criteria

Abstract

Approximately 85% of multiple sclerosis (MS) cases begin as clinically isolated syndromes (CIS). Results from the Controlled High-Risk Subjects Avonex^® Multiple Sclerosis Prevention Study (CHAMPS) demonstrated that, in patients with CIS, treatment with intramuscular (IM) interferon beta-1a (IFNβ-1a) 30 μg once weekly delayed conversion to clinically definite MS (CDMS) in the total population and in subgroups based on presenting syndromes and baseline magnetic resonance imaging (MRI) characteristics. Changes to clinical and MRI risk classification of presenting symptoms in recent studies prompted reanalysis of CHAMPS data. Presenting syndromes were assessed using a derived algorithm that stratifies patients into mono- or multifocal categories based on functional system scores. The ability of IM IFNβ-1a to delay progression to CDMS in subgroups based on clinical presentation and MRI characteristics was assessed. Reanalysis of CHAMPS patients showed that 30% could be classified by clinical criteria as having multifocal disease at baseline. IM IFNβ-1a initiated at a first demyelinating attack delayed CDMS in monofocal patients (P = 0.0013), patients with or without gadolinium-enhancing lesions (P = 0.0007, P = 0.0405) and patients with at least nine T2 lesions at baseline (P = 0.0044). These data confirm that IM IFNβ-1a delays conversion to CDMS in patients with CIS.

Keywords

clinically definite multiple sclerosis clinically isolated syndrome intramuscular interferon beta-1a

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References

1 Miller D Barkhof F Montalban X Thompson A Filippi M . Clinically isolated syndromes suggestive of multiple sclerosis, part 1: natural history, pathogenesis, diagnosis, and prognosis. Lancet Neurol 2005; 4: 281–288.

2 Frohman EM Goodin DS Calabresi PA . The utility of MRI in suspected MS. Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2003; 61: 602–611.

3 IFNB Multiple Sclerosis Study Group . Interferon beta-1a is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology 1993; 43: 655–661.

4 Jacobs LD Cookfair DL Rudick RA . Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. Ann Neurol 1996; 39: 285–294.

5 PRISMS . (Prevention of Relapses and Disability by Interferon β-1a Subcutaneously in Multiple Sclerosis) Study Group. Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. Lancet 1998; 352: 1498–1504.

6 PRISMS . (Prevention of Relapses and Disability by Interferon-β-1a Subcutaneously in Multiple Sclerosis) Study Group, University of British Columbia MS/MRI Analysis Group. PRISMS-4: long-term efficacy of interferon-beta-1a in relapsing MS. Neurology 2001; 56: 1628–1636.

7 Jacobs LD Beck RW Simon JH . Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. N Engl J Med 2000; 343: 898–904.

8 The CHAMPIONS Study Group . IM interferon β-1a delays definite multiple sclerosis 5 years after a first demyelinating event. Neurology 2006; 66: 678–684.

9 Beck RW Chandler DL Cole SR . Interferon β-1a for early multiple sclerosis: CHAMPS trial subgroup analyses. Ann Neurol 2002; 51: 481–490.

10.

10 McDonald WI Compston A Edan G . Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 2001; 50: 121–127.

11.

11 Uitdehaag BMJ Kappos L Bauer L . Discrepancies in the interpretation of clinical symptoms and signs in the diagnosis of multiple sclerosis. A proposal for standardization. Mult Scler 2005; 11: 227–231.

12.

12 Kappos L Polman CH Freedman MS . Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes. Neurology 2006; 67: 944–953.

13.

13 Zipoli V Portaccio E Siracusa G . Interobserver agreement on Poser’s and the new McDonald’s diagnostic criteria for multiple sclerosis. Mult Scler 2003; 9: 481–485.

14.

14 Comi G Filippi M Barkhof F . Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. Lancet 2001; 357: 1576–1582.

15.

15 Poser CM Paty DW Scheinberg L . New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 1983; 13: 227–231.

16.

16 The CHAMPS Study Group . Predictors of short-term disease activity following a first clinical demyelinating event: analysis of the CHAMPS placebo group. Mult Scler 2002; 8: 405–409.

17.

17 O’Connor P . The effects of intramuscular interferon beta-1a in patients at high risk for development of multiple sclerosis: a post hoc analysis of data from CHAMPS. Clin Ther 2003; 25: 2865–2874.

18.

18 O’Connor PW Miller D Riester K . Relapse rates and enhancing lesions in a phase II trial of natalizumab in multiple sclerosis. Mult Scler 2005; 11: 568–572.

19.

19 Optic Neuritis Study Group . The 5-year risk of MS after optic neuritis: experience of the Optic Neuritis Treatment Trial. Neurology 1997; 49: 1404–1413.

20.

20 Polman CW Kappos L Freedman MS . Subgroups of the BENEFIT study: risk of developing MS and treatment effect of interferon beta-1b. J Neurol 2008; 255: 480–487.