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Original Contribution |

Enhanced Benefit of Increasing Interferon Beta-1a Dose and Frequency in Relapsing Multiple Sclerosis:  The EVIDENCE Study FREE

Steven R. Schwid, MD; John Thorpe, MD; Mohammad Sharief, MD; Magnhild Sandberg-Wollheim, MD; Kottil Rammohan, MD; Jeanette Wendt, MD; Hillel Panitch, MD; Douglas Goodin, MD; David Li, MD; Peter Chang, PhD; Gordon Francis, MD ; EVIDENCE (Evidence of Interferon Dose-Response: European North American Comparative Efficacy) Study Group and the University of British Columbia MS/MRI Research Group
[+] Author Affiliations

Financial Disclosure: Drs Schwid, Thorpe, Sharief, Sandberg-Wollheim, Rammohan, Wendt, Panitch, Goodin, and Li have received research funding and honoraria from Serono International SA. Drs Chang and Francis are employees of Serono International SA, which sponsored the study.


Arch Neurol. 2005;62(5):785-792. doi:10.1001/archneur.62.5.785.
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Published online

Background  The EVIDENCE (Evidence of Interferon Dose-Response: European North American Comparative Efficacy) Study demonstrated that patients with multiple sclerosis (MS) who initiate interferon beta-1a therapy with 44 μg 3 times weekly (TIW) were less likely to have a relapse or activity on magnetic resonance imaging (MRI) compared with those who initiate therapy at a dosage of 30 μg 1 time weekly (QW).

Objective  To determine the effect of changing the dosage from 30 μg QW to 44 μg TIW in this extension of the EVIDENCE Study.

Design/Patients  Patients with relapsing MS originally randomized to interferon beta-1a, 30 μg QW, during the comparative phase of the study changed to 44 μg TIW, whereas patients originally randomized to 44 μg TIW continued that regimen. Patients were followed up, on average, for an additional 32 weeks.

Main Outcome Measure  The within-patient pretransition to posttransition change in relapse rate.

Results  At the transition visit, 223 (73%) of 306 patients receiving 30 μg QW converted to 44 μg TIW, and 272 (91%) of 299 receiving 44-μg TIW continued the same therapy. The posttransition annualized relapse rate decreased from 0.64 to 0.32 for patients increasing the dose (P<.001) and from 0.46 to 0.34 for patients continuing 44-μg TIW (P = .03). The change was greater in those increasing dose and frequency (P = .047). Patients converting to the 44-μg TIW regimen had fewer active lesions on T2-weighted MRI compared with before the transition (P = .02), whereas those continuing the 44-μg TIW regimen had no significant change in T2 active lesions. Patients who converted to high-dose/high-frequency interferon beta-1a therapy had increased rates of adverse events and treatment terminations consistent with the initiation of high-dose subcutaneous interferon therapy.

Conclusions  Patients receiving interferon beta-1a improved on clinical and MRI disease measures when they changed from 30μg QW to 44 μg TIW.

Correspondence: Steven R. Schwid, MD, Department of Neurology, University of Rochester, 601 Elmwood Ave, Box 605, Rochester, NY 14642 (steven_schwid@urmc.rochester.edu).

Accepted for Publication: November 5, 2004.

Author Affiliations: Departments of Neurology, University of Rochester, Rochester, NY (Dr Schwid), Cambridge University, Cambridge, England (Dr Thorpe), Guy’s Hospital, London, England (Dr Sharief), University Hospital, Lund, Sweden (Dr Sandberg-Wollheim), The Ohio State University, Columbus (Dr Rammohan), University of Vermont College of Medicine, Burlington (Dr Panitch), and University of California-San Francisco (Dr Goodin); Tucson Neurology Associates, Tucson, Ariz (Dr Wendt); Department of Radiology, University of British Columbia, Vancouver (Dr Li); and Serono Inc, Rockland, Mass (Drs Chang and Francis).

Author Contributions:Study concept and design: Li and Francis. Acquisition of data: Schwid, Thorpe, Sharief, Sandberg-Wollheim, Rammohan, Wendt, Panitch, Goodin, Chang, and Francis. Analysis and interpretation of data: Schwid, Thorpe, Sandberg-Wollheim, Rammohan, Wendt, Panitch, Goodin, Li, and Francis. Drafting of the manuscript: Schwid, Goodin, and Francis. Critical revision of the manuscript for important intellectual content: Schwid, Thorpe, Sharief, Sandberg-Wollheim, Rammohan, Wendt, Panitch, Li, Chang, and Francis. Statistical analysis: Goodin and Chang. Obtained funding: Francis. Administrative, technical, and material support: Sharief, Wendt, and Francis. Study supervision: Rammohan, Li, and Francis.

Funding/Support: This study was supported by Serono International SA, Geneva, Switzerland.

REFERENCES

Williams  GJWitt  PL Comparative study of the pharmacodynamic and pharmacologic effects of Betaseron and Avonex. J Interferon Cytokine Res199818967975
PubMed
Stürzebecher  SMaibauer  RHeuner  ABeckmann  KAufdembrinke  B Pharmacodynamic comparison of single doses of IFN-β1a and IFN-β1b in healthy volunteers. J Interferon Cytokine Res19991912571264
PubMed
Rothuizen  LEBuclin  TSpertinei  F  et al Influence of interferon β-1a dose frequency of PBMC cytokine secretion and biological effect markers. J Neuroimmunol199999131141
PubMed
IFNβ Multiple Sclerosis Study Group Interferon beta-1b is effective in relapsing-remitting multiple sclerosis, I: clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology199343655661
PubMed
IFNB Multiple Sclerosis Study Group,; University of British Columbia MS/MRI Analysis Group Interferon beta-1b in the treatment of multiple sclerosis: final outcome of the randomized controlled trial. Neurology19954512771285
PubMed
PRISMS Study Group Randomised double-blind placebo-controlled study of interferon β-1a in relapsing/remitting multiple sclerosis. Lancet199835214981504
PubMed
Li  DKPaty  DW Magnetic resonance imaging results of the PRISMS trial: a randomized, double-blind, placebo-controlled study of interferon-β1a in relapsing-remitting multiple sclerosis. Ann Neurol199946197206
PubMed
PRISMS Study Group; , University of British Columbia MS/MRI Analysis Group PRISMS-4: long-term efficacy of interferon-β-1a in relapsing MS. Neurology20015616281636
PubMed
Clanet  MRadue  EWKappos  L  et al A randomized, double-blind, dose-comparison study of weekly interferon β-1a in relapsing MS. Neurology20025915071517
PubMed
Panitch  HGoodin  DSFrancis  G  et al Randomized, comparative study of interferon β-1a treatment regimens in MS: the EVIDENCE Trial. Neurology20025914961506
PubMed
Panitch  H Differences between IFN beta-1A 44 mcg TIW and 30 mcg QW sustained to 16 months: final EVIDENCE results [abstract]. Int J MS Care2003580
Poser  CMPaty  DWScheinberg  L  et al New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol198313227231
PubMed
Abdul-Ahad  AGalazka  ARRevel  MBiffoni  MBorden  EC Incidence of antibodies to interferon-β in patients treated with recombinant human interferon-β1a from mammalian cells. Cytokines Cell Mol Ther199732732
PubMed
Munafo  ATrinchard-Lugan  IINguyen  TXBuraglio  M Comparative bioavailability of recombinant human interferon beta-1a after intramuscular and subcutaneous administration. Eur J Neurol19985187193
PubMed
Durelli  LVerdun  EBarbero  P  et al Every-other-day interferon beta-1b versus once-weekly interferon beta-1a for multiple sclerosis: results of a 2-year prospective randomised multicentre study (INCOMIN). Lancet200235914531460
PubMed

Figures

Tables

References

Williams  GJWitt  PL Comparative study of the pharmacodynamic and pharmacologic effects of Betaseron and Avonex. J Interferon Cytokine Res199818967975
PubMed
Stürzebecher  SMaibauer  RHeuner  ABeckmann  KAufdembrinke  B Pharmacodynamic comparison of single doses of IFN-β1a and IFN-β1b in healthy volunteers. J Interferon Cytokine Res19991912571264
PubMed
Rothuizen  LEBuclin  TSpertinei  F  et al Influence of interferon β-1a dose frequency of PBMC cytokine secretion and biological effect markers. J Neuroimmunol199999131141
PubMed
IFNβ Multiple Sclerosis Study Group Interferon beta-1b is effective in relapsing-remitting multiple sclerosis, I: clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology199343655661
PubMed
IFNB Multiple Sclerosis Study Group,; University of British Columbia MS/MRI Analysis Group Interferon beta-1b in the treatment of multiple sclerosis: final outcome of the randomized controlled trial. Neurology19954512771285
PubMed
PRISMS Study Group Randomised double-blind placebo-controlled study of interferon β-1a in relapsing/remitting multiple sclerosis. Lancet199835214981504
PubMed
Li  DKPaty  DW Magnetic resonance imaging results of the PRISMS trial: a randomized, double-blind, placebo-controlled study of interferon-β1a in relapsing-remitting multiple sclerosis. Ann Neurol199946197206
PubMed
PRISMS Study Group; , University of British Columbia MS/MRI Analysis Group PRISMS-4: long-term efficacy of interferon-β-1a in relapsing MS. Neurology20015616281636
PubMed
Clanet  MRadue  EWKappos  L  et al A randomized, double-blind, dose-comparison study of weekly interferon β-1a in relapsing MS. Neurology20025915071517
PubMed
Panitch  HGoodin  DSFrancis  G  et al Randomized, comparative study of interferon β-1a treatment regimens in MS: the EVIDENCE Trial. Neurology20025914961506
PubMed
Panitch  H Differences between IFN beta-1A 44 mcg TIW and 30 mcg QW sustained to 16 months: final EVIDENCE results [abstract]. Int J MS Care2003580
Poser  CMPaty  DWScheinberg  L  et al New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol198313227231
PubMed
Abdul-Ahad  AGalazka  ARRevel  MBiffoni  MBorden  EC Incidence of antibodies to interferon-β in patients treated with recombinant human interferon-β1a from mammalian cells. Cytokines Cell Mol Ther199732732
PubMed
Munafo  ATrinchard-Lugan  IINguyen  TXBuraglio  M Comparative bioavailability of recombinant human interferon beta-1a after intramuscular and subcutaneous administration. Eur J Neurol19985187193
PubMed
Durelli  LVerdun  EBarbero  P  et al Every-other-day interferon beta-1b versus once-weekly interferon beta-1a for multiple sclerosis: results of a 2-year prospective randomised multicentre study (INCOMIN). Lancet200235914531460
PubMed

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