Disease-modifying drugs for multiple sclerosis and subsequent health service use

Ng, Huah Shin; Zhu, Feng; Kingwell, Elaine; Zhao, Yinshan; Yao, Shenzhen; Ekuma, Okechukwu; Svenson, Lawrence W.; Evans, Charity; Fisk, John D.; Marrie, Ruth Ann; Tremlett, Helen

doi:10.1177/13524585211063403

Cited by 6 publications

(12 citation statements)

References 34 publications

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“…Nevertheless, the greater availability of higher efficacy DMTs may associate with lower indirect costs of MS, by allowing people with MS to stay longer and be more productive in the workforce, 15 as well as lead to decreased direct costs by reducing hospitalisation rates and slowing the progression of disability. 20,21 It is also worth to note that the private spending was not included in this analysis. However, due to universal coverage of medications listed on the PBS, apart from co-payments up to defined safety net thresholds, there is a negligible private expenditure on registered medications in the Australian healthcare setting.…”

Section: Discussionmentioning

confidence: 99%

The disease-modifying therapy utilisation and cost trend for multiple sclerosis in Australia between 2013 and 2022

Zhao,

Taylor,

Campbell

et al. 2023

Mult Scler

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Background: The MS disease-modifying therapies (DMTs) prescribing landscape in Australia have changed over time. Objectives: This study evaluated the utilisation and cost trends of MS-related DMTs in Australia over 10 years and investigated differences between States/Territories. Methods: The prescription and costs of 16 DMTs were extracted from the Pharmaceutical Benefits Scheme for 2013–2022. Descriptive approaches analysed the total number of people prescribed DMTs and total DMT costs per 10,000 population, proportions of prescriptions/costs by DMT groups and the number of people prescribed each individual DMT and costs of each DMT over the 10-year period. All estimates were for Australia and each State/Territory individually. Results: The number of people prescribed DMT and costs per 10,000 population had substantial growth between 2013 and 2022: 125%/164% for Australia, and 94%–251%/129%–373% for individual States/Territories. Higher efficacy group accounted for 54% of total people prescribed DMTs in 2013 and 75% in 2022. Fingolimod was the most popular DMT until 2020, then was dominated by ocrelizumab. The trends of individual DMT prescriptions and costs differed between states particularly in Western Australia (WA), Tasmania and Northern Territory (NT). Conclusion: DMT prescriptions and costs continuously increased over the last decade, particularly for higher efficacy DMTs, and their trends differed between States/Territories.

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Section: Discussionmentioning

confidence: 99%

The disease-modifying therapy utilisation and cost trend for multiple sclerosis in Australia between 2013 and 2022

Zhao,

Taylor,

Campbell

et al. 2023

Mult Scler

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“… 17 Comorbidity was measured by the Charlson Comorbidity Index (CCI), using diagnostic codes in hospital/physician (primary/secondary care) claims data in the year pre-index date, excluding hemiplegia/paraplegia. 19 This index has been widely used in MS and other populations, including the examination of long-term mortality, 16 other DMD-related outcomes, 20 , 21 and adverse drug events. 22 , 23 The index also captures several common comorbidities, including those most relevant to specific contraindications/cautions for DMD use, such as cardiovascular, cerebrovascular, chronic lung and liver diseases, diabetes, and malignancy.…”

Section: Methodsmentioning

confidence: 99%

Adverse Events Associated With Disease-Modifying Drugs for Multiple Sclerosis

Ng,

Zhu,

Zhao

et al. 2024

Neurology

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Background and Objectives It is not possible to fully establish the safety of a disease-modifying drug (DMD) for multiple sclerosis (MS) from randomized controlled trials as only very common adverse events occurring over the short-term can be captured, and the quality of reporting has been variable. We examined the relationship between the DMDs for MS and potential adverse events in a multiregion population-based study. Methods We identified people with MS using linked administrative health data from 4 Canadian provinces. MS cases were followed from the most recent of first MS or related demyelinating disease event on January 1, 1996, until the earliest of emigration, death, or December 31, 2017. DMD exposure primarily comprised β-interferon, glatiramer acetate, natalizumab, fingolimod, dimethyl fumarate, teriflunomide, and alemtuzumab. We examined associations between DMD exposure and infection-related hospitalizations and physician visits using recurrent events proportional means models and between DMD exposure and 15 broad categories of incident adverse events using stratified multivariate Cox proportional hazard models. Results We identified 35,894 people with MS. While virtually all DMDs were associated with a 42%–61% lower risk of infection-related hospitalizations, there was a modest increase in infection-related physician visits by 10%–33% for select DMDs. For incident adverse events, most elevated risks involved a second-generation DMD, with alemtuzumab's hazard of thyroid disorders being 19.42 (95% CI 9.29–36.51), hypertension 4.96 (95% CI 1.78–13.84), and cardiovascular disease 3.72 (95% CI 2.12–6.53). Natalizumab's highest risk was for cardiovascular disease (adjusted hazard ratio [aHR] 1.61; 95% CI 1.24–2.10). For the oral DMDs, fingolimod was associated with higher hazards of cerebrovascular (aHR 2.04; 95% CI 1.27–3.30) and ischemic heart diseases (aHR 1.64; 95% CI 1.10–2.44) and hypertension (aHR 1.73; 95% CI 1.30–2.31); teriflunomide with higher hazards of thyroid disorders (aHR 2.30; 95% CI 1.11–4.74), chronic liver disease (aHR 1.94; 95% CI 1.19–3.18), hypertension (aHR 1.76; 95% CI 1.32–2.37), and hyperlipidemia (aHR 1.61; 95% CI 1.07–2.44); and from complementary analyses (in 1 province), dimethyl fumarate with acute liver injury (aHR 6.55; 95% CI 1.96–21.87). Discussion Our study provides an extensive safety profile of several different DMDs used to treat MS in the real-world setting. Our findings not only complement those observed in short-term clinical trials but also provide new insights that help inform the risk-benefit profile of the DMDs used to treat MS in clinical practice. The results of this study highlight the continued need for long-term, independent safety studies of the DMDs used to treat MS. Classification of Evidence This study provides Class III evidence that for patients with MS, while DMD exposure reduces the risk of infection-related hospital...

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“…Hospitalization data included day surgery/minor procedures (but not drug infusions e.g., for natalizumab or alemtuzumab) ( 28 ). For the hospitalizations, any overlapping admissions or any new admission that occurred within one day of the previous hospitalization were counted as a single event ( 10 , 29 ). For the physician visits, multiple claims with the same primary ICD code captured on the same day were counted as a single visit ( 10 , 29 ).…”

Section: Methodsmentioning

confidence: 99%

“…For the hospitalizations, any overlapping admissions or any new admission that occurred within one day of the previous hospitalization were counted as a single event ( 10 , 29 ). For the physician visits, multiple claims with the same primary ICD code captured on the same day were counted as a single visit ( 10 , 29 ). Neurologist visits were also excluded from the count as the number of these visits was anticipated to be higher in persons exposed to a DMD (versus no DMD) as part of routine care ( 4 ) (other physician specialties cannot prescribe an MS DMD in British Columbia).…”

Section: Methodsmentioning

confidence: 99%

Disease-Modifying Drug Uptake and Health Service Use in the Ageing MS Population

Graf

Zhu

et al. 2022

Front. Immunol.

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BackgroundEvidence regarding the efficacy or effectiveness of the disease-modifying drugs (DMDs) in the older multiple sclerosis (MS) population is scarce. This has contributed to a lack of evidence-based treatment recommendations for the ageing MS population in practice guidelines. We examined the relationship between age (<55 and ≥55 years), DMD exposure and health service use in the MS population.MethodsWe conducted a population-based observational study using linked administrative health data from British Columbia, Canada. We selected all persons with MS and followed from the most recent of their first MS or demyelinating event, 18th birthday or 01-January-1996 (index date) until the earliest of emigration, death or 31-December-2017 (study end). We assessed DMD exposure status over time, initially as any versus no DMD, then by generation (first or second) and finally by each individual DMD. Age-specific analyses were conducted with all-cause hospitalizations and number of physician visits assessed using proportional means model and negative binomial regression with generalized estimating equations.ResultsWe included 19,360 persons with MS (72% were women); 10,741/19,360 (56%) had ever reached their 55th birthday. Person-years of follow-up whilst aged <55 was 132,283, and 93,594 whilst aged ≥55. Any DMD, versus no DMD in the <55-year-olds was associated with a 23% lower hazard of hospitalization (adjusted hazard ratio, aHR0.77; 95%CI 0.72-0.82), but not in the ≥55-year-olds (aHR0.95; 95%CI 0.87-1.04). Similar patterns were observed for the first and second generation DMDs. Exposure to any (versus no) DMD was not associated with rates of physician visits in either age group (<55 years: adjusted rate ratio, aRR1.02; 95%CI 1.00-1.04 and ≥55 years: aRR1.00; 95%CI 0.96-1.03), but variation in aRR was observed across the individual DMDs.ConclusionOur study showed beneficial effects of the DMDs used to treat MS on hospitalizations for those aged <55 at the time of exposure. In contrast, for individuals ≥55 years of age exposed to a DMD, the hazard of hospitalization was not significantly lowered. Our study contributes to the broader understanding of the potential benefits and risks of DMD use in the ageing MS population.

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Disease-modifying drugs for multiple sclerosis and subsequent health service use

Cited by 6 publications

References 34 publications

The disease-modifying therapy utilisation and cost trend for multiple sclerosis in Australia between 2013 and 2022

The disease-modifying therapy utilisation and cost trend for multiple sclerosis in Australia between 2013 and 2022

Adverse Events Associated With Disease-Modifying Drugs for Multiple Sclerosis

Disease-Modifying Drug Uptake and Health Service Use in the Ageing MS Population

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