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

Abstract

Objective: We assessed the relationship between the multiple sclerosis (MS) disease-modifying drugs (DMDs) and healthcare use.

Methods: Persons with MS (aged ⩾18 years) were identified using linked population-based health administrative data in four Canadian provinces and were followed from the most recent of their first MS/demyelinating event or 1 January 1996 until the earliest of death, emigration, or study end (31 December 2017 or 31 March 2018). Prescription records captured DMD exposure, examined as any DMD, then by generation (first-generation (the injectables) or second-generation (orals/infusions)) and individual DMD. The associations with subsequent all-cause hospitalizations and physician visits were examined using proportional means model and negative binomial regression.

Results: Of 35,894 MS cases (72% female), mean follow-up was 12.0 years, with person-years of DMD exposure for any, or any first- or second-generation DMD being 63,290, 54,605 and 8685, respectively. Any DMD or any first-generation DMD exposure (versus non-exposure) was associated with a 24% lower hazard of hospitalization (adjusted hazard ratio, aHR: 0.76; 95% confidence intervals (CIs): 0.71-0.82), rising to 29% for the second-generation DMDs (aHR: 0.71; 95% CI: 0.58-0.88). This ranged from 18% for teriflunomide (aHR: 0.82; 95% CI: 0.67-1.00) to 44% for fingolimod (aHR: 0.56; 95% CI: 0.36-0.87). In contrast, DMD exposure was generally not associated with substantial differences in physician visits.

Conclusion: Findings provide real-world evidence of a beneficial relationship between DMD exposure and hospitalizations.

Trial registration: ClinicalTrials.gov NCT04472975.

Keywords: Disease-modifying drugs; health services; hospitalization; multiple sclerosis; physician services.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: H.S.N. receives funding from the Multiple Sclerosis Society of Canada’s endMS Postdoctoral Fellowship and the Michael Smith Foundation for Health Research Trainee Award. During the past year, H.S.N. has received funding from the Canadian Institutes of Health Research (CIHR) Drug Safety and Effectiveness Cross-Disciplinary Training Program. F.Z. has no conflicts of interests relevant to this study. E.K. has no conflicts of interests relevant to this study. Y.Z. has no conflicts of interests relevant to this study. S.Y. has no conflicts of interests relevant to this study. O.E. has no conflicts of interests relevant to this study. L.W.S. has no conflicts of interests relevant to this study. C.E. receives funding from CIHR. J.D.F. receives research funding from CIHR, Multiple Sclerosis Society of Canada, Crohn’s and Colitis Canada, Research Nova Scotia; consultation and distribution royalties from MAPI Research Trust. R.A.M. receives research funding from CIHR, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, CMSC and the US Department of Defense, and is a co-investigator on studies receiving funding from Biogen Idec and Roche Canada. H.T. is the Canada Research Chair for Neuroepidemiology and Multiple Sclerosis. Current research support received from the National Multiple Sclerosis Society, the Canadian Institutes of Health Research, the Multiple Sclerosis Society of Canada, and the Multiple Sclerosis Scientific Research Foundation. In addition, in the last 5 years, has received research support from the UK MS Trust; travel expenses to present at CME conferences from the Consortium of MS Centres (2018), the National MS Society (2016, 2018), ECTRIMS/ACTRIMS (2015, 2016, 2017, 2018, 2019, 2020), and American Academy of Neurology (2015, 2016, 2019). Speaker honoraria are either declined or donated to an MS charity or to an unrestricted grant for use by H.T.’s research group.

Figures

Figure 1.

Exposure to disease-modifying drugs for multiple sclerosis and hazard of hospitalization in a population-based cohort. CI: confidence interval; DMD: disease-modifying drug. Bold indicates p < 0.05. aResults from each of the four provinces were adjusted for sex, socioeconomic status (quintiles) closest to the index date, and the following characteristics over time: age (continuous), calendar year (continuous), and comorbidity score (categorized as 0, 1, 2, ⩾ 3) measured using a modified Charlson Comorbidity Index and were then combined using random-effects meta-analyses. bPerson-years of follow-up for the calculation of crude rate were as per Table 1 except the duration of a hospitalization was discounted from the follow-up time to avoid immortal time bias. cAll beta-interferon products were considered as one class.

Figure 2.

Exposure to disease-modifying drugs for multiple sclerosis and rates of physician service use. CI: confidence interval; DMD: disease-modifying drug. Bold indicates p < 0.05. aResults from each of the four provinces were adjusted for sex, socioeconomic status (quintiles) closest to the index date, and the following characteristics over time: age (continuous), calendar year (continuous), and comorbidity score (categorized as 0, 1, 2, ⩾3) measured using a modified Charlson Comorbidity Index and were then combined using random-effects meta-analyses. bPerson-years of follow-up/exposure are shown in Table 1 and were used to calculate the crude rates. cAll beta-interferon products were considered as one class.

Figure 3.

Exposure to disease-modifying drugs for multiple sclerosis and hazard of hospitalization by sex. CI: confidence interval; DMD: disease-modifying drug; S: small event rates prevented generation of reliable estimates. Bold indicates p < 0.05. aResults from each of the four provinces were adjusted for socioeconomic status (quintiles) closest to the index date and the following characteristics over time: age (continuous), calendar year (continuous), and comorbidity score (categorized as 0, 1, 2, ⩾3) measured using a modified Charlson Comorbidity Index and were then combined using random-effects meta-analyses. Hazard ratios were estimated by introducing interaction terms between sex and DMD exposure variables. bAll beta-interferon products were considered as one class.

Figure 4.

Exposure to disease-modifying drugs for multiple sclerosis and rates of physician service use by sex. CI, confidence interval; DMD, disease-modifying drug. Bold indicates p < 0.05. aResults from each of the four provinces were adjusted for socioeconomic status (quintiles) closest to the index date and the following characteristics over time: age (continuous), calendar year (continuous), and comorbidity score (categorized as 0, 1, 2, ⩾3) measured using a modified Charlson Comorbidity Index and were then combined using random-effects meta-analyses. Rate ratios were estimated by introducing interaction terms between sex and DMD exposure variables. bAll beta-interferon products were considered as one class.

Figure 5.

Exposure to disease-modifying drugs for multiple sclerosis and rates of physician visits by physician specialties. aResults from four provinces were combined and the crude rate was calculated using the formula: (total number of physician claims for each specialty by DMD exposure status/total person years of follow-up by DMD exposure status) × 100. The results for general practitioner were shown in the right square box with a separate y-axis value (i.e. with a 10 times higher y-axis value than the remaining physician specialties). bAll beta-interferon products were considered as one class. *As per the data privacy and access agreements, small cell size (