Background: Multiple sclerosis (MS) is a chronic, incurable disease of the central nervous system (CNS) and a potentially severe cause of neurological disability throughout adult life. Typically diagnosed between the ages of 20 and 40, the disease is associated with a severely impaired health-related quality of life and a high societal economic impact. About 85% of patients are initially diagnosed with relapsing-remitting MS (RRMS), which is characterized by the unpredictable occurrence of relapses. Clinically, a relapse is defined as a worsening or appearance of new neurological symptoms followed by a period of partial or complete recovery (relapse without worsening, RWW). Up to 80% of patients transit to the secondary progressive course (SPMS) within 20 years. SPMS is marked by an accumulation of irreversible disability either resulting from relapse-associated worsening (RAW) or progression independent of relapse activity (PIRA). Even though health economic assessments are well established in MS, implications of relapses and disability worsening on societal economic costs have scarcely been studied. Regarding disability worsening it is known that annual costs increase with increasing disability from 21,174–28,200€ (EDSS 0–3) to 39,923–44,000€ (EDSS 4–6.5) (in 2015 values). However, the impact of PIRA and RAW on societal costs remains not well understood. Research to date has shown that the societal economic burden of MS increases in periods of relapses with most recent estimates at 2468€ per relapse (in 2015 values). The results of relapse cost analyses are inconsistent between studies since relapses and associated costs can vary across and within individuals depending on disease severity, disease duration, age, gender or therapy. However, a comprehensive test of this hypothesis is still needed. Research aims: I investigated the societal economic costs of disability worsening and relapses in patients with MS. First, I determined the societal economic costs of patients achieving disease activity free status (DAF, neither relapses nor disability worsening) and compared them with those having PIRA and RAW events. Second, I estimated direct and indirect relapse costs and determined differences in costs related to patient characteristics. Furthermore, I described the pharmacoeconomic impact during the relapse follow-up.
Methods: Two-year clinical and pharmacoeconomic data were derived from two single arm, prospective, multicenter, non-interventional long term studies conducted in Germany applying the Multiple Sclerosis Health Resource Survey (MS-HRS). The MS-HRS estimates the MS-associated direct and indirect costs from a societal perspective using the most accurate form of bottom-up microcosting. Costs are presented per quarter in 2011 Euros. PIRA and RAW events were indicated through a roving confirmed disability worsening (CDW) measure and corresponding relapse assessments. CDW is based on a predefined increase on the Expanded Disability Status Scale (EDSS) sustained over at least 6 months. The effects of PIRA and RAW on total, direct medical, direct non-medical and indirect societal economic costs are adjusted for age, gender and EDSS. Due to the right skewness of cost data, I applied a Generalized Linear Mixed Model (GLMM) with a negative binomial distribution. Patients achieving DAF were assigned as the reference group. I calculated relapse costs as the difference in quarterly costs between propensity score (PS) matched patients with and without relapses (1:1 ratio). Statistical differences in relapse costs between patient and disease strata were derived from a Generalized Linear Model (GLM) with a negative binomial distribution. For relapse active patients, I additionally calculated the difference between quarterly costs prior- and during relapse and determined costs in the post-relapse quarter.
Results: Overall, 1959 patients were analyzed with typical patient characteristics for a clinical RRMS population. Patients reported an average age of 41.62±10.04 years and were mostly female (73%). The mean disease duration was 7.30±5.95 with a mean baseline EDSS value of 2.26±1.37. Total mean quarterly societal economic costs including disease-modifying therapies (DMTs) were 6929€±2886€ per patient averaged over two years. Excluding DMTs, patients achieving DAF status had total mean quarterly costs of 1703€±2489€. PIRA caused 29% (IRR: 1.29; 95% CI 1.06–1.50, p<0.05) higher total costs compared to DAF. On the contrary, RAW increased total costs by factor 1.56 (95% CI 1.30–1.87, p<0.001). The effect of PIRA and RAW was striking for direct medical costs which increased by factor 1.48 (95% CI 1.13–1.95, p<0.01) and 2.25 (95% CI 1.72–2.94, p<0.001), respectively. In the relapse cost analyses, a total of 1882 patients were included encompassing 607 (32%) relapse-active patients. After PS-matching, 597 active and inactive patients were retained. Relapse costs ranged between 690€ (age: 50+ years) and 1729€ (disease du-ration: <5 years). In mildly disabled and recently diagnosed patients, indirect relapse costs (range: 971€-1093€) constantly outweighed direct costs (range: 535€-636€). The increase from prior- to relapse quarter was strongest for inpatient stays (+364%, 390€; p<0.001), day admissions (+241%, 53€; p<0.001) and absenteeism (+127%, 419€; p<0.001). In the post-relapse quarter direct costs and costs of absenteeism remained elevated for patients with relapse associated worsening.
Conclusion: For the case of MS, disease activity should be a focus in medical research to reduce the societal economic burden of the disease. Disability worsening is associated with significantly higher societal economic costs compared to DAF status in patients with MS. Accordingly, it is highly important from a societal perspective to delay or even prevent transition into the progressive phase of MS. That is another argument for treating MS patients early with appropriate DMTs. Furthermore, relapses significantly increase the societal economic burden of MS. From a health economic societal perspective, the prevention of relapses in young patients and those with a recent diagnosis should be a particular focus.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:73245 |
| Date | 21 December 2020 |
| Creators | Neß, Nils-Henning |
| Contributors | Ziemssen, Tjalf, Kugler, Joachim, Technische Universität Dresden |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | German |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:doctoralThesis, info:eu-repo/semantics/doctoralThesis, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 10.2196/17921, 10.1007/s40273-020-00917-3, 10.1007/s00415-019-09676-4 |
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