Investigation of heterogeneity in the association between interferon beta and disability progression in multiple sclerosis: An observational study

A. Shirani, Y. Zhao, M. E. Karim, J. Petkau, P. Gustafson, C. Evans, E. Kingwell, M. L. van der Kop, J. Oger, H. Tremlett

Research output: Contribution to journalArticle

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Abstract

Background and purpose: It was recently reported that there was no significant overall association between interferon beta exposure and disability progression in relapsing-remitting multiple sclerosis (RRMS) patients in an observational study from Canada. In the current study, the potential for heterogeneity in the association between exposure to interferon beta and disability progression across patients' baseline characteristics was investigated. Methods: RRMS patients treated with interferon beta (n = 868) and two cohorts of untreated patients (829 contemporary and 959 historical controls) were included. The main outcome was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained Expanded Disability Status Scale (EDSS) score 6 using a multivariable Cox model, with treatment as a time-varying predictor, testing interaction effects for five pre-specified baseline characteristics: sex, age, disease duration, EDSS and annualized relapse rate (ARR) based on the previous 2 years. Results: Significant heterogeneity was found in the association of interferon beta exposure and disability progression only across ARR, and only when treated patients were compared with historical controls (P = 0.005 at a Bonferroni-adjusted alpha of 0.01). For patients with ARR>1, treatment-exposed time was associated with a hazard ratio of 0.38 (95%CI 0.20-0.75) for disability progression compared with the unexposed time. Conclusions: RRMS patients with more frequent relapses at baseline may be more likely to benefit from interferon beta treatment with respect to long-term disability progression.

Original languageEnglish (US)
Pages (from-to)835-844
Number of pages10
JournalEuropean Journal of Neurology
Volume21
Issue number6
DOIs
StatePublished - Jun 2014

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Interferon-beta
Multiple Sclerosis
Observational Studies
Relapsing-Remitting Multiple Sclerosis
Recurrence
Therapeutics
Proportional Hazards Models
Sex Characteristics
Canada

Keywords

  • British Columbia
  • Disability progression
  • Interferon beta
  • Multiple sclerosis
  • Observational studies

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Investigation of heterogeneity in the association between interferon beta and disability progression in multiple sclerosis : An observational study. / Shirani, A.; Zhao, Y.; Karim, M. E.; Petkau, J.; Gustafson, P.; Evans, C.; Kingwell, E.; van der Kop, M. L.; Oger, J.; Tremlett, H.

In: European Journal of Neurology, Vol. 21, No. 6, 06.2014, p. 835-844.

Research output: Contribution to journalArticle

Shirani, A, Zhao, Y, Karim, ME, Petkau, J, Gustafson, P, Evans, C, Kingwell, E, van der Kop, ML, Oger, J & Tremlett, H 2014, 'Investigation of heterogeneity in the association between interferon beta and disability progression in multiple sclerosis: An observational study', European Journal of Neurology, vol. 21, no. 6, pp. 835-844. https://doi.org/10.1111/ene.12324
Shirani, A. ; Zhao, Y. ; Karim, M. E. ; Petkau, J. ; Gustafson, P. ; Evans, C. ; Kingwell, E. ; van der Kop, M. L. ; Oger, J. ; Tremlett, H. / Investigation of heterogeneity in the association between interferon beta and disability progression in multiple sclerosis : An observational study. In: European Journal of Neurology. 2014 ; Vol. 21, No. 6. pp. 835-844.
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AU - Gustafson, P.

AU - Evans, C.

AU - Kingwell, E.

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AB - Background and purpose: It was recently reported that there was no significant overall association between interferon beta exposure and disability progression in relapsing-remitting multiple sclerosis (RRMS) patients in an observational study from Canada. In the current study, the potential for heterogeneity in the association between exposure to interferon beta and disability progression across patients' baseline characteristics was investigated. Methods: RRMS patients treated with interferon beta (n = 868) and two cohorts of untreated patients (829 contemporary and 959 historical controls) were included. The main outcome was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained Expanded Disability Status Scale (EDSS) score 6 using a multivariable Cox model, with treatment as a time-varying predictor, testing interaction effects for five pre-specified baseline characteristics: sex, age, disease duration, EDSS and annualized relapse rate (ARR) based on the previous 2 years. Results: Significant heterogeneity was found in the association of interferon beta exposure and disability progression only across ARR, and only when treated patients were compared with historical controls (P = 0.005 at a Bonferroni-adjusted alpha of 0.01). For patients with ARR>1, treatment-exposed time was associated with a hazard ratio of 0.38 (95%CI 0.20-0.75) for disability progression compared with the unexposed time. Conclusions: RRMS patients with more frequent relapses at baseline may be more likely to benefit from interferon beta treatment with respect to long-term disability progression.

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