Beta-interferon exposure and onset of secondary progressive multiple sclerosis.

BACKGROUND AND PURPOSE: Beta-interferons (IFNß) are the most widely prescribed drugs for patients with multiple sclerosis (MS). However, whether or not treatment with IFNß can delay secondary progressive MS (SPMS) onset remains unknown. Our aim was to examine the association between IFNß exposure and SPMS onset in patients with relapsing-remitting MS (RRMS). METHODS: A retrospective cohort study using British Columbia (Canada) population-based clinical and health administrative data (1985-2008) was conducted. RRMS patients treated with IFNß (n = 794) were compared with untreated contemporary (n = 933) and historical (n = 837) controls. Cohort entry was the first clinic visit during which patients became eligible for IFNß treatment (baseline). The outcome was time from baseline to SPMS onset. Cox regression models with IFNß as a time-dependent exposure were adjusted for sex, and baseline age, disease duration, disability, *socioeconomic status and *comorbidities (*available for the contemporary cohorts only). Additional analyses included propensity score adjustment. RESULTS: The median follow-up for the IFNß-treated, untreated contemporary and historical controls were 5.7, 3.7 and 7.3 years, and the proportions of patients reaching SPMS were 9.2%, 11.8% and 32.9%, respectively. After adjustment for confounders, IFNß exposure was not associated with the risk of reaching SPMS when either the contemporary or the historical untreated cohorts were considered (hazard ratio 1.07; 95% confidence interval 0.93-1.48, and hazard ratio 1.04; 95% confidence interval 0.74-1.46, respectively). Further adjustments and the propensity score yielded results consistent with the main analysis. CONCLUSIONS: Amongst patients with RRMS, use of IFNß was not associated with a delayed onset of SPMS.

Birth outcomes of pregnancies fathered by men with multiple sclerosis.

We linked several population-based clinical and health administrative databases in British Columbia, Canada. We identified and compared birth outcomes of pregnancies fathered by men with multiple sclerosis (MS) (n=202) and men from a frequency-matched general population cohort (n=981) between 1996 and 2010. Using multivariate models, we analyzed the association of paternal MS, disease duration at conception and disability (as measured by the Expanded Disability Status Scale) with birth weight and gestational age. Paternal MS and MS-related clinical factors were not significantly associated with birth outcomes (p>0.05). This study provides assurance to expecting fathers with MS and their families.

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

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.

Relative mortality and survival in multiple sclerosis: findings from British Columbia, Canada.

OBJECTIVE: To examine mortality and factors associated with survival in a population based multiple sclerosis (MS) cohort. METHODS: Clinical and demographic data of MS patients registered with the British Columbia MS clinics (1980-2004) were linked to provincial death data, and patients were followed until death, emigration or study end (31 December 2007). Absolute survival and the influence of patient characteristics (sex, disease course (primary progressive (PPMS) vs relapsing onset (R-MS)) and onset age) were estimated by Kaplan-Meier analyses (from birth and disease onset). Mortality relative to the general population was examined using standardised mortality ratios. Excess mortality associated with patient characteristics and time period of cohort entry was assessed by relative survival modelling. RESULTS: Of 6917 patients, 1025 died. Median survival age was 78.6 years (95% CI 77.5 to 79.7) for women and 74.3 years (95% CI 73.1 to 75.4) for men. Survival from onset was longer for R-MS (49.7 years; 95% CI 47.9 to 51.5) than for PPMS (32.5 years; 95% CI 29.5 to 35.7); however, survival age was similar. The overall standardised mortality ratios was 2.89 (95% CI 2.71 to 3.07), and patients survived approximately 6 years less than expected, relative to the general population. PPMS had a higher relative mortality risk compared with R-MS (relative mortality ratio (RMR) 1.52; 95% CI 1.30 to 1.80). Women with PPMS had a relative survival disadvantage compared with men with PPMS (RMR 1.55; 95% CI 1.19 to 2.01). Relative survival within 10 years of cohort entry was similar between time periods. CONCLUSIONS: Some of the longest MS survival times are reported here but the risk of death was still greater than in the age, sex and calendar year matched general population. No evidence of increased survival over time was found when improved survival in the general population was taken into consideration.