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

Kingwell, Elaine; Kop, Mia van der; Zhao, Yinshan; Shirani, Afsaneh; Zhu, Feng; Oger, Joël; Tremlett, Helen

doi:10.1136/jnnp-2011-300616

Cited by 138 publications

(154 citation statements)

References 38 publications

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“…To date, however, only natural history populations have been investigated in studies of sufficient duration. [11][12][13] Questions about the impact of any DMTs on long-term outcomes remain unanswered. To provide data for the impact of therapy on survival, we analyzed survival in patients 21 years after their enrollment into the original IFN␤-1b RCT.…”

Section: Discussionmentioning

confidence: 99%

Survival in MS

Goodin¹,

Reder²,

Ebers³

et al. 2012

Neurology

222

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Objective: To examine the effects of interferon beta (IFN␤)-1b on all-cause mortality over 21 years in the cohort of 372 patients who participated in the pivotal randomized clinical trial (RCT), retaining (in the analysis) the original randomized treatment-assignments. Methods:For this randomized long-term cohort study, the primary outcome, defined before data collection, was the comparison of all-cause mortality between the IFN␤-1b 250 g and placebo groups from the time of randomization through the entire 21-year follow-up interval (intention-totreat, log-rank test for Kaplan-Meier survival curves). All other survival outcomes were secondary.Results: After a median of 21.1 years from RCT enrollment, 98.4% (366 of 372) of patients were identified, and, of these, 81 deaths were recorded (22.1% [81 of 366]). Patients originally randomly assigned to IFN␤-1b 250 g showed a significant reduction in all-cause mortality over the 21-year period compared with placebo (p ϭ 0.0173), with a hazard ratio of 0.532 (95% confidence interval 0.314-0.902). The hazard rate of death at long-term follow-up by Kaplan-Meier estimates was reduced by 46.8% among IFN␤-1b 250 g-treated patients (46.0% among IFN␤-1b 50 g-treated patients) compared with placebo. Baseline variables did not influence the observed treatment effect. Conclusions:There was a significant survival advantage in this cohort of patients receiving early IFN␤-1b treatment at either dose compared with placebo. Near-complete ascertainment, together with confirmatory findings from both active treatment groups, strengthens the evidence for an IFN␤-1b benefit on all-cause mortality. Classification of Evidence:This study provides Class III evidence that early treatment with IFN␤-1b is associated with prolonged survival in initially treatment-naive patients with relapsingremitting multiple sclerosis. Neurology Multiple sclerosis (MS) is a chronic, inflammatory disease of the CNS with a lifelong course, necessitating outcome assessments over both the short term and long term.1 However, randomized clinical trials (RCTs) have typically focused only on short-term outcomes such as clinical measures of relapse and physical disability, as well as MRI measures of disease activity and severity.2-8 Although survival is the ultimate long-term outcome, to date mortality in patients with MS treated with disease-modifying therapy (DMT) has not been well-studied, largely because of the length and completeness of observation needed. 9 *These authors contributed equally to this work.

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Section: Discussionmentioning

confidence: 99%

Survival in MS

Goodin¹,

Reder²,

Ebers³

et al. 2012

Neurology

222

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“…26 This means that the projected mortality for people with MS decreased at the same rate as for Canadians living without MS, largely consistent with observations in British Columbia. 27 Using the BC administrative data prevalence cohort, we examined the number of deaths among individuals with MS, and compared it to the death rate among individuals without a neurological condition.…”

Section: Ms Status: Incidencementioning

confidence: 99%

Multiple sclerosis in Canada 2011 to 2031: results of a microsimulation modelling study of epidemiological and economic impacts

Amankwah

Marrie

Bancej

et al. 2017

Health Promot Chronic Dis Prev Can

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“…The 6-year interim analyses used the British Columbia cohort, which was initiated in 1980, before DMTs were made routinely available in Canada. This cohort has prospectively recorded EDSS scores and covers about 80% of the relevant MS population in that area, providing a rich source of data about the natural history of MS. 152,153 Patients from the British Columbia cohort who would have met the criteria for prescribing IFN-β or GA were selected for comparison with those in the UK RSS. [153][154][155] Analysis of the 6-year data of the UK clinical cohort, comparing disease progression against the historical comparator cohort, suggested that, on the whole, the DMTs included in the RSS reduced disability progression and did so to the agreed level of cost-effectiveness.…”

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confidence: 99%

Clinical effectiveness and cost-effectiveness of beta-interferon and glatiramer acetate for treating multiple sclerosis: systematic review and economic evaluation

Melendez‐Torres

Auguste

Armoiry

et al. 2017

Health Technol Assess

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Background At the time of publication of the most recent National Institute for Health and Care Excellence (NICE) guidance [technology appraisal (TA) 32] in 2002 on beta-interferon (IFN-β) and glatiramer acetate (GA) for multiple sclerosis, there was insufficient evidence of their clinical effectiveness and cost-effectiveness. Objectives To undertake (1) systematic reviews of the clinical effectiveness and cost-effectiveness of IFN-β and GA in relapsing–remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS) and clinically isolated syndrome (CIS) compared with best supportive care (BSC) and each other, investigating annualised relapse rate (ARR) and time to disability progression confirmed at 3 months and 6 months and (2) cost-effectiveness assessments of disease-modifying therapies (DMTs) for CIS and RRMS compared with BSC and each other. Review methods Searches were undertaken in January and February 2016 in databases including The Cochrane Library, MEDLINE and the Science Citation Index. We limited some database searches to specific start dates based on previous, relevant systematic reviews. Two reviewers screened titles and abstracts with recourse to a third when needed. The Cochrane tool and the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) and Philips checklists were used for appraisal. Narrative synthesis and, when possible, random-effects meta-analysis and network meta-analysis (NMA) were performed. Cost-effectiveness analysis used published literature, findings from the Department of Health’s risk-sharing scheme (RSS) and expert opinion. A de novo economic model was built for CIS. The base case used updated RSS data, a NHS and Personal Social Services perspective, a 50-year time horizon, 2014/15 prices and a discount rate of 3.5%. Outcomes are reported as incremental cost-effectiveness ratios (ICERs). We undertook probabilistic sensitivity analysis. Results In total, 6420 publications were identified, of which 63 relating to 35 randomised controlled trials (RCTs) were included. In total, 86% had a high risk of bias. There was very little difference between drugs in reducing moderate or severe relapse rates in RRMS. All were beneficial compared with BSC, giving a pooled rate ratio of 0.65 [95% confidence interval (CI) 0.56 to 0.76] for ARR and a hazard ratio of 0.70 (95% CI, 0.55 to 0.87) for time to disability progression confirmed at 3 months. NMA suggested that 20 mg of GA given subcutaneously had the highest probability of being the best at reducing ARR. Three separate cost-effectiveness searches identified > 2500 publications, with 26 included studies informing the narrative synthesis and model inputs. In the base case using a modified RSS the mean incremental cost was £31,900 for pooled DMTs compared with BSC and the mean incremental quality-adjusted life-years (QALYs) were 0.943, giving an ICER of £33,800 per QALY gained for people with RRMS. In probabilistic sensitivity analysis the ICER was £34,000 per QALY gained. In sensitivity analysis, using the assessment group inputs gave an ICER of £12,800 per QALY gained for pooled DMTs compared with BSC. Pegylated IFN-β-1 (125 µg) was the most cost-effective option of the individual DMTs compared with BSC (ICER £7000 per QALY gained); GA (20 mg) was the most cost-effective treatment for CIS (ICER £16,500 per QALY gained). Limitations Although we built a de novo model for CIS that incorporated evidence from our systematic review of clinical effectiveness, our findings relied on a population diagnosed with CIS before implementation of the revised 2010 McDonald criteria. Conclusions DMTs were clinically effective for RRMS and CIS but cost-effective only for CIS. Both RCT evidence and RSS data are at high risk of bias. Research priorities include comparative studies with longer follow-up and systematic review and meta-synthesis of qualitative studies. Study registration This study is registered as PROSPERO CRD42016043278. Funding The National Institute for Health Research Health Technology Assessment programme.

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

Cited by 138 publications

References 38 publications

Survival in MS

Survival in MS

Multiple sclerosis in Canada 2011 to 2031: results of a microsimulation modelling study of epidemiological and economic impacts

Clinical effectiveness and cost-effectiveness of beta-interferon and glatiramer acetate for treating multiple sclerosis: systematic review and economic evaluation

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