Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis

Afsaneh Shirani, Yinshan Zhao, Mohammad Ehsanul Karim, Charity Evans, Elaine Kingwell, Mia L. Van Der Kop, Joel Oger, Paul Gustafson, John Petkau, Helen Tremlett

Research output: Contribution to journalArticle

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Abstract

Context: Interferon beta is widely prescribed to treat multiple sclerosis (MS); however, its relationship with disability progression has yet to be established. Objective: To investigate the association between interferon beta exposure and disability progression in patients with relapsing-remitting MS. Design, Setting, and Patients: Retrospective cohort study based on prospectively collected data (1985-2008) from British Columbia, Canada. Patients with relapsing-remitting MS treated with interferon beta (n=868) were compared with untreated contemporary (n=829) and historical (n=959) cohorts. Main Outcome Measures: The main outcome measure was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained score of 6 (requiring a cane to walk 100 m; confirmed at >150 days with no measurable improvement) on the Expanded Disability Status Scale (EDSS) (range, 0-10, with higher scores indicating higher disability). A multivariable Cox regression model with interferon beta treatment included as a time-varying covariate was used to assess the hazard of disease progression associated with interferon beta treatment. Analyses also included propensity score adjustment to address confounding by indication. Results: The median active follow-up times (first to last EDSS measurement) were as follows: for the interferon beta-treated cohort, 5.1 years (interquartile range [IQR], 3.0-7.0 years); for the contemporary control cohort, 4.0 years (IQR, 2.1-6.4 years); and for the historical control cohort, 10.8 years (IQR, 6.3-14.7 years). The observed outcome rates for reaching a sustained EDSS score of 6 were 10.8%, 5.3%, and 23.1% in the 3 cohorts, respectively. After adjustment for potential baseline confounders (sex, age, disease duration, and EDSS score), exposure to interferon beta was not associated with a statistically significant difference in the hazard of reaching an EDSS score of 6 when either the contemporary control cohort (hazard ratio, 1.30; 95% CI, 0.92-1.83; P=.14) or the historical control cohort (hazard ratio, 0.77; 95% CI, 0.58-1.02; P=.07) were considered. Further adjustment for comorbidities and socioeconomic status, where possible, did not change interpretations, and propensity score adjustment did not substantially change the results. Conclusion: Among patients with relapsing-remitting MS, administration of interferon beta was not associated with a reduction in progression of disability.

Original languageEnglish (US)
Pages (from-to)247-256
Number of pages10
JournalJAMA - Journal of the American Medical Association
Volume308
Issue number3
DOIs
StatePublished - Jul 18 2012

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Relapsing-Remitting Multiple Sclerosis
Interferon-beta
Safety Management
Propensity Score
Outcome Assessment (Health Care)
Canes
British Columbia
Proportional Hazards Models
Social Class
Multiple Sclerosis
Canada
Disease Progression
Comorbidity
Cohort Studies
Therapeutics
Retrospective Studies

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis. / Shirani, Afsaneh; Zhao, Yinshan; Karim, Mohammad Ehsanul; Evans, Charity; Kingwell, Elaine; Van Der Kop, Mia L.; Oger, Joel; Gustafson, Paul; Petkau, John; Tremlett, Helen.

In: JAMA - Journal of the American Medical Association, Vol. 308, No. 3, 18.07.2012, p. 247-256.

Research output: Contribution to journalArticle

Shirani, A, Zhao, Y, Karim, ME, Evans, C, Kingwell, E, Van Der Kop, ML, Oger, J, Gustafson, P, Petkau, J & Tremlett, H 2012, 'Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis', JAMA - Journal of the American Medical Association, vol. 308, no. 3, pp. 247-256. https://doi.org/10.1001/jama.2012.7625
Shirani, Afsaneh ; Zhao, Yinshan ; Karim, Mohammad Ehsanul ; Evans, Charity ; Kingwell, Elaine ; Van Der Kop, Mia L. ; Oger, Joel ; Gustafson, Paul ; Petkau, John ; Tremlett, Helen. / Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis. In: JAMA - Journal of the American Medical Association. 2012 ; Vol. 308, No. 3. pp. 247-256.
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abstract = "Context: Interferon beta is widely prescribed to treat multiple sclerosis (MS); however, its relationship with disability progression has yet to be established. Objective: To investigate the association between interferon beta exposure and disability progression in patients with relapsing-remitting MS. Design, Setting, and Patients: Retrospective cohort study based on prospectively collected data (1985-2008) from British Columbia, Canada. Patients with relapsing-remitting MS treated with interferon beta (n=868) were compared with untreated contemporary (n=829) and historical (n=959) cohorts. Main Outcome Measures: The main outcome measure was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained score of 6 (requiring a cane to walk 100 m; confirmed at >150 days with no measurable improvement) on the Expanded Disability Status Scale (EDSS) (range, 0-10, with higher scores indicating higher disability). A multivariable Cox regression model with interferon beta treatment included as a time-varying covariate was used to assess the hazard of disease progression associated with interferon beta treatment. Analyses also included propensity score adjustment to address confounding by indication. Results: The median active follow-up times (first to last EDSS measurement) were as follows: for the interferon beta-treated cohort, 5.1 years (interquartile range [IQR], 3.0-7.0 years); for the contemporary control cohort, 4.0 years (IQR, 2.1-6.4 years); and for the historical control cohort, 10.8 years (IQR, 6.3-14.7 years). The observed outcome rates for reaching a sustained EDSS score of 6 were 10.8{\%}, 5.3{\%}, and 23.1{\%} in the 3 cohorts, respectively. After adjustment for potential baseline confounders (sex, age, disease duration, and EDSS score), exposure to interferon beta was not associated with a statistically significant difference in the hazard of reaching an EDSS score of 6 when either the contemporary control cohort (hazard ratio, 1.30; 95{\%} CI, 0.92-1.83; P=.14) or the historical control cohort (hazard ratio, 0.77; 95{\%} CI, 0.58-1.02; P=.07) were considered. Further adjustment for comorbidities and socioeconomic status, where possible, did not change interpretations, and propensity score adjustment did not substantially change the results. Conclusion: Among patients with relapsing-remitting MS, administration of interferon beta was not associated with a reduction in progression of disability.",
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T1 - Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis

AU - Shirani, Afsaneh

AU - Zhao, Yinshan

AU - Karim, Mohammad Ehsanul

AU - Evans, Charity

AU - Kingwell, Elaine

AU - Van Der Kop, Mia L.

AU - Oger, Joel

AU - Gustafson, Paul

AU - Petkau, John

AU - Tremlett, Helen

PY - 2012/7/18

Y1 - 2012/7/18

N2 - Context: Interferon beta is widely prescribed to treat multiple sclerosis (MS); however, its relationship with disability progression has yet to be established. Objective: To investigate the association between interferon beta exposure and disability progression in patients with relapsing-remitting MS. Design, Setting, and Patients: Retrospective cohort study based on prospectively collected data (1985-2008) from British Columbia, Canada. Patients with relapsing-remitting MS treated with interferon beta (n=868) were compared with untreated contemporary (n=829) and historical (n=959) cohorts. Main Outcome Measures: The main outcome measure was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained score of 6 (requiring a cane to walk 100 m; confirmed at >150 days with no measurable improvement) on the Expanded Disability Status Scale (EDSS) (range, 0-10, with higher scores indicating higher disability). A multivariable Cox regression model with interferon beta treatment included as a time-varying covariate was used to assess the hazard of disease progression associated with interferon beta treatment. Analyses also included propensity score adjustment to address confounding by indication. Results: The median active follow-up times (first to last EDSS measurement) were as follows: for the interferon beta-treated cohort, 5.1 years (interquartile range [IQR], 3.0-7.0 years); for the contemporary control cohort, 4.0 years (IQR, 2.1-6.4 years); and for the historical control cohort, 10.8 years (IQR, 6.3-14.7 years). The observed outcome rates for reaching a sustained EDSS score of 6 were 10.8%, 5.3%, and 23.1% in the 3 cohorts, respectively. After adjustment for potential baseline confounders (sex, age, disease duration, and EDSS score), exposure to interferon beta was not associated with a statistically significant difference in the hazard of reaching an EDSS score of 6 when either the contemporary control cohort (hazard ratio, 1.30; 95% CI, 0.92-1.83; P=.14) or the historical control cohort (hazard ratio, 0.77; 95% CI, 0.58-1.02; P=.07) were considered. Further adjustment for comorbidities and socioeconomic status, where possible, did not change interpretations, and propensity score adjustment did not substantially change the results. Conclusion: Among patients with relapsing-remitting MS, administration of interferon beta was not associated with a reduction in progression of disability.

AB - Context: Interferon beta is widely prescribed to treat multiple sclerosis (MS); however, its relationship with disability progression has yet to be established. Objective: To investigate the association between interferon beta exposure and disability progression in patients with relapsing-remitting MS. Design, Setting, and Patients: Retrospective cohort study based on prospectively collected data (1985-2008) from British Columbia, Canada. Patients with relapsing-remitting MS treated with interferon beta (n=868) were compared with untreated contemporary (n=829) and historical (n=959) cohorts. Main Outcome Measures: The main outcome measure was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained score of 6 (requiring a cane to walk 100 m; confirmed at >150 days with no measurable improvement) on the Expanded Disability Status Scale (EDSS) (range, 0-10, with higher scores indicating higher disability). A multivariable Cox regression model with interferon beta treatment included as a time-varying covariate was used to assess the hazard of disease progression associated with interferon beta treatment. Analyses also included propensity score adjustment to address confounding by indication. Results: The median active follow-up times (first to last EDSS measurement) were as follows: for the interferon beta-treated cohort, 5.1 years (interquartile range [IQR], 3.0-7.0 years); for the contemporary control cohort, 4.0 years (IQR, 2.1-6.4 years); and for the historical control cohort, 10.8 years (IQR, 6.3-14.7 years). The observed outcome rates for reaching a sustained EDSS score of 6 were 10.8%, 5.3%, and 23.1% in the 3 cohorts, respectively. After adjustment for potential baseline confounders (sex, age, disease duration, and EDSS score), exposure to interferon beta was not associated with a statistically significant difference in the hazard of reaching an EDSS score of 6 when either the contemporary control cohort (hazard ratio, 1.30; 95% CI, 0.92-1.83; P=.14) or the historical control cohort (hazard ratio, 0.77; 95% CI, 0.58-1.02; P=.07) were considered. Further adjustment for comorbidities and socioeconomic status, where possible, did not change interpretations, and propensity score adjustment did not substantially change the results. Conclusion: Among patients with relapsing-remitting MS, administration of interferon beta was not associated with a reduction in progression of disability.

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