Healthcare utilization in multiple sclerosis: impact of disease modifying therapies and comorbidities

Multiple Sclerosis (MS) is a chronic neurological condition associated with relapses, disability accrual over time, and high rates of healthcare utilization. Earlier diagnosis and development of highly effective disease modifying therapies (DMTs) have shifted the utilization of healthcare from management of acute relapses and their sequelae in the inpatient setting to the outpatient setting, where relapse prevention and modification of disability progression are the mainstay of treatment. Despite this change, the economic burden of both direct and indirect costs related to MS remains significant.^1-2 Lifetime direct medical costs of MS are estimated to be $4.8 million, which makes it the second most expensive chronic condition only behind heart failure.³

Previous studies have demonstrated correlation between utility and costs with disease severity,⁴ and the increasing use of newer highly effective DMTs has been associated with an increased risk of serious infections resulting in hospitalization.⁵ Apart from MS-related disease characteristics, differences in healthcare organization, comorbidities, demographic elements, and psychosocial factors also remain important yet generally understudied contributors to healthcare utilization in this population.

This issue of Multiple Sclerosis Journal features two observational, population-based studies which examine various aspects of healthcare utilization amongst people with MS. Moccia et. al.⁶ utilized routinely collected healthcare data of people with MS living in the Campania Region of southern Italy from 2015-2019 to examine utilization of emergency medical care and predictors of emergency admissions and outcomes. They found that 17% required emergency medical care over 5 years, and that the risk of admission increased with age (hazard ratio (HR) 1.02; 1.01-1.03) and comorbidities (with each point increase in the Charlson comorbidity index⁷ (HR 1.62; 1.54-1.71)). The risk of admission due to increased age was modest and may not be clinically significant. Risk of admission decreased in patients using DMTs with higher adherence (HR 0.18; 0.89-1.27), for both MS-related and non-neurologic causes. Most admissions were determined to be primarily related to MS (70%). These findings demonstrate more favorable outcomes for patients on (and adherent to) DMTs and suggest that coordinated management of comorbidities may reduce hospitalization rates and related costs. The strengths of this study include the robust analysis of discharge diagnoses (specifically pertaining to MS and non-MS-related conditions and comorbidities) and the population-based nature of the study which lessens selection bias. One limitation is that data were not evaluated on an individual level, raising concern for missingness of data and/or inaccuracy. Additionally, disability status and sociodemographic data (such as race and ethnicity) are lacking, reducing the ability to account for influences of social determinants of health.

Ng et. al.⁸ report the results of a study assessing healthcare utilization of MS patients on DMTs in four Canadian provinces using population-based administrative data from 1996-2018, examining all-cause hospitalizations and physician visits. DMT exposure was associated with lower hazard of hospitalization, ranging from 18-44% depending on DMT type, with an adjusted hazard ratio (aHR) of 0.76 (0.71-0.81) for first-generation DMTs and 0.71 (0.58-0.88) for second-generation DMTs. DMT use was also associated with a trend towards lower rates of physician visits. These findings suggest a beneficial relationship between DMT use and healthcare utilization. This study has several strengths, including a large population, inclusion of all physician visits and hospitalizations at the individual level, and a long timeframe (22 years) over which the study was conducted. One concern is that only 29% of the study population had a DMT exposure, and only a small proportion were on newer monoclonal antibody treatments. This may diminish the understanding of DMT impact on utilization outcomes. Additionally, the use of administrative data restricts the ability to examine disease characteristics such as disease duration, disability level, and relapse rate which might explain these low rates of DMT use. Lastly, the data regarding the physician specialty visit types is informative, but since the main conclusion of the paper is regarding hospitalization, discharge diagnosis data would have been of interest.

These studies are of value because there is little current information regarding general healthcare utilization in MS, especially in the context of DMT use. Both studies demonstrate improved outcomes in patients treated with DMT. This is important considering the concerns surrounding risk for serious infections and hospitalizations associated with use of the newer highly effective DMTs. Again, Moccia et. al. report no differences in likelihood of death due to emergency admission or discharge to a long-term care facility based on treatment group, and Ng et. al. report lower rates of hospitalization with any DMT exposure across all DMT types. Though additional long-term safety studies are needed, these results provide valuable insights as to the long-term benefits of DMT use.

Both studies also highlight the benefit of comprehensive care. Management of MS is complex and requires individualized treatment. Multidisciplinary care has long been recognized as beneficial, not only with regards to patient-related outcomes but also its implications for research.⁹ Routine use of multidisciplinary MS care units has been proposed as a cost-effective solution to improve functionality and quality of life in people with MS.¹⁰ However, this model remains understudied and its value has yet to be proven in randomized controlled studies.¹¹ These two real-world studies provide evidence to support coordinated management and should prompt further investigation.

Lastly, both studies were conducted in countries with universal healthcare coverage. Because differences in healthcare organization contribute so greatly to referral practices and emergency care utilization, similar studies in countries without universal healthcare coverage will be necessary to better understand these patterns.

Examining healthcare utilization amongst people with MS is important in understanding the complex interaction between treatment, comorbidities, and system-related factors. Although these studies provide insight into the patterns of healthcare utilization amongst people with MS, additional studies to better understand healthcare utilization, the optimal structure of comprehensive care delivery, and the impact of comprehensive care on MS-related outcomes in diverse healthcare organization models are needed.