Shifting from the treat-to-target to the early highly effective treatment approach in patients with multiple sclerosis - real-world evidence from Germany.

Background: While evidence highlights the effectiveness of initiating disease-modifying therapy with a high-efficacy medication for multiple sclerosis (MS) patients with poor prognostic factors, it remains unclear whether this approach has been adopted by a broad range of MS providers in Germany yet. Objective: To assess the adoption of the early highly effective treatment (EHT) compared to the treat-to-target treatment approach with the option of escalating treatment efficacy over time in Germany based on real-world evidence data. Design: Patient-level pharmacy dispensing data from the Permea platform were analysed from 2020 to 2022. Methods: In total, 29,529 therapy beginners (>18 years) were included to analyse shifts in treatment approaches over time and switching behaviour. Medication classification adhered to the German Society of Neurology guidelines and designated fumarates, glatiramer acetate, teriflunomide and interferons as low-efficacy category 1 medications; cladribine and S1P-modulators as medium-efficacy category 2 medications; and alemtuzumab, natalizumab, ocrelizumab, ofatumumab and rituximab (off-label) as high-efficacy category 3 medications. Results: Our results show that 70.0% of patients redeemed their first prescription for category 1 medication, 16.3% for category 2 and 13.7% for category 3 medications. The proportion of prescriptions filled shifted from 2020 to 2022 with a decrease of 14.7% for category 1 drugs and an increase of 12.5% for category 3 drugs. 93.2% of patients stayed on their initially prescribed medication category. 3.2% of category 1 and 3.7% of category 2 therapy beginners escalated to category 3 medication. 3.4% of category 3 medication users de-escalated their treatment to category 1 or category 2. Conclusion: While most individuals started their treatment according to the treat-to-target approach and remained on their initially prescribed medication category, there has been a steadily increasing shift towards the EHT approach since 2020. These insights demonstrate that, while not officially recommended by German guidelines, MS providers increasingly adopt the EHT approach.

Comparing the long-term clinical and economic impact of ofatumumab versus dimethyl fumarate and glatiramer acetate in patients with relapsing multiple sclerosis: A cost-consequence analysis from a societal perspective in Germany.

Background: Evidence suggests that early highly efficacious therapy in relapsing multiple sclerosis is superior to escalation strategies. Objective: A cost-consequence analysis simulated different treatment scenarios with ofatumumab (OMB), dimethyl fumarate (DMF) and glatiramer acetate (GA): immediate OMB initiation as first treatment, early switch to OMB after 1 year on DMF/GA, late switch after 5 years or no switch. Methods: An EDSS-based Markov model with a 10-year time horizon was applied. Cycle transitions included EDSS progression, improvement or stabilization, treatment discontinuation, relapse or death. Input data were extracted from OMB trials, a network meta-analysis, published literature, and publicly available sources. Results: The late switch compared to the immediate OMB scenario resulted in a lower proportion of patients with EDSS 0-3 (Δ - 7.5% DMF; Δ - 10.3% GA), more relapses (Δ + 0.72 DMF; Δ + 1.23 GA) and lower employment rates (Δ - 4.0% DMF; Δ - 5.6% GA). The same applies to late versus early switches. No switch scenarios resulted in worse outcomes. Higher drug acquisition costs in the immediate OMB and early switch scenarios were almost compensated by lower costs for patient care and productivity loss. Conclusion: Immediate OMB treatment and an early switch improves clinical and productivity outcomes while remaining almost cost neutral compared to late or no switches.

[The Multiple Sclerosis Health Resource Utilization Survey]. / Der Multiple Sclerosis Health Resource Utilization Survey.

BACKGROUND: In health economic studies, valid and reliable cost data are essential to reach meaningful conclusions. In the case of multiple sclerosis (MS), such studies are often based on primary data for which the underlying survey instruments have not been published. In addition, heterogeneous methods make the comparability and interpretation of such study results difficult. To standardize health economic studies in MS, the Multiple Sclerosis Health Resource Utilization Survey (MS-HRS) was developed, validated and published in a freely accessible format. RESEARCH QUESTION: This review focuses on the MS-HRS. We report on the methodological background of studies on the assessment of cost of illness as well as MS-HRS-based results on the costs of disease dynamics in people with MS. METHODS: This article is based on a selective literature review on the MS-HRS as well as on health economic aspects of cost assessment. RESULTS: The MS-HRS provides a holistic assessment of direct medical, direct non-medical and indirect resource utilization. Within indirect costs, we considered absenteeism, either short term (sick leave) or long term (disability pension), but also presenteeism, which refers to impaired performance during work. Resources were valued at the societal opportunity cost or the best possible approximation. First analyses based on MS-HRS showed that, in addition to inpatient disease severity and clinical course, disease dynamics in form of relapses and progression have enormous socioeconomic implications. CONCLUSION: Valid cost data bring transparency to the economic consequences of diseases. In addition to clinical data, cost data can be used to determine cost-effectiveness and thus reveal opportunities for more efficient patient care. For the case of MS, a freely accessible tool is available for cost assessments.

Cost of illness in multiple sclerosis by disease characteristics - A review of reviews.

INTRODUCTION: In light of the increasing number of economic burden studies and heterogeneity in methodology and reporting standards, there is a need for robust evidence synthesis on an umbrella review level. AREAS COVERED: We performed the first review of reviews of cost-of-illness studies in multiple sclerosis. Focusing on disaggregated costs by disease characteristics (disability level, relapse, disease course), we also characterized the underlying methodological evidence base of individual (primary) studies. EXPERT COMMENTARY: We identified 17 reviews encompassing 111 unique primary studies, and a high degree of overlap across reviews. Costs were substantial, rising with disability level, relapse episodes, and disease progression. Disability was the key cost driver. Compared to mild disability, total costs for moderate disability were 1.4-2.3-fold higher and 1.8-2.9-fold higher for severe disability. With escalating disability, the share of costs outside the health system (indirect costs, informal care) increasingly outweighed the share of direct medical costs. Of all 111 primary studies, 72% gathered resource use/loss data by patient self-report. Associated costs were mostly reported by disability level (75%), followed by relapse (48%) and disease course (21%). In conclusion, although heterogeneity can make in-depth comparisons of costs across studies impossible, important patterns are broadly apparent.

Gender disparities in health resource utilization in patients with relapsing-remitting multiple sclerosis: a prospective longitudinal real-world study with more than 2000 patients.

BACKGROUND: For the case of multiple sclerosis, research on gender differences from a health economics perspective has not received much attention. However, cost-of-illness analyses can provide valuable information about the diverse impact of the disease and thus help decision-makers to allocate scarce resources. The aim of this study was to describe healthcare resource use and associated societal costs from a gender perspective. In particular, we aimed to identify how resource utilization potentially differs in certain cost components between men and women. METHODS: Clinical and economic data were extracted from two prospective, multicentre, non-interventional, observational studies in Germany. Information on health resource use was obtained from all patients on a quarterly basis using a validated questionnaire.Cost analyses were conducted from the societal perspective including all direct (healthcare-related) and indirect (work-related) costs, regardless of who bears them. Gender-related differences were analysed by a multivariable generalized linear model with a negative binomial distribution and log link function due to the right-skewed distribution pattern of cost data. In addition, costs for men and women were descriptively analysed within subgroups of two-year disease activity. RESULTS: In total, 2095 patients (women-to-men ratio of 2.7:1) presented a mean age of 41.85 years and a median Expanded Disability Status Scale of 2 (interquartile range 1-3.5) (p > 0.30 for gender-related differences). Women and men did not statistically differ in total quarterly costs (€2329 ± €2570 versus €2361 ± €2612). For both, costs were higher with advancing disease severity and indirect costs were the main societal cost driver. Regarding healthcare-related resources, women incurred higher costs for ambulant consultations [incidence rate ratio (IRR) 1.16, confidence interval (CI) 1.04-1.31], complementary medicine (IRR 2.41, CI 1.14-5.06), medical consumables (IRR 2.53, CI 1.69-3.79) and informal care (IRR 2.79, CI 1.56-5.01). Among indirect costs, we found higher costs for men for presenteeism (IRR 0.62; CI 0.53-0.72) and higher costs for women for disability pension (IRR 1.62; CI 1.23-2.13). CONCLUSIONS: Multiple sclerosis poses a significant economic burden on patients, families and society. While the total economic burden did not differ between male and female patients, we found gender differences in specific cost items that are similar to those in the wider non-MS population.

Real-World Evidence on the Societal Economic Relapse Costs in Patients with Multiple Sclerosis.

BACKGROUND: Relapses are the hallmark of multiple sclerosis (MS). Analyses have shown that the cost of MS increases during periods of relapse. However, results are inconsistent between studies, possibly due to different study designs and the different implications of relapses with respect to patient characteristics. OBJECTIVES: The aims were to estimate and describe direct and indirect relapse costs and to determine differences in costs with respect to patient characteristics. Furthermore, we describe the pharmacoeconomic impact during the relapse follow-up. METHODS: Data were extracted from two German, multicenter, observational studies applying a validated resource costs instrument. Relapse costs were calculated as the difference in quarterly costs between propensity score (PS)-matched patients with and without relapses (1:1 ratio). For relapse active patients, we additionally calculated the difference between quarterly costs prior to and during relapse and determined costs in the post-relapse quarter. RESULTS: Of 1882 patients, 607 (32%) presented at least one relapse. After PS-matching, 597 relapse active and relapse inactive patients were retained. Relapse costs (in 2019 values) ranged between €791 (age 50 + years) and €1910 (disease duration < 5 years). In mildly disabled and recently diagnosed patients, indirect relapse costs (range €1073-€1207) constantly outweighed direct costs (range €591-€703). The increase from prior quarter to relapse quarter was strongest for inpatient stays (+ 366%, €432; p < 0.001), day admissions (+ 228%, €57; p < 0.001), and absenteeism (127%, €463; p < 0.001). In the post-relapse quarter, direct costs and costs of absenteeism remained elevated for patients with relapse-associated worsening. CONCLUSION: A recent diagnosis and mild disability lead to high relapse costs. The results suggest the necessity to incorporate patient characteristics when assessing relapse costs.

Correction to: Real-World Evidence on the Patterns of Increased Societal Economic Relapse Costs in Patients with Multiple Sclerosis.

In the original version of this article, the title of the article has been published incorrectly.

The Multiple Sclerosis Health Resource Utilization Survey (MS-HRS): Development and Validation Study.

BACKGROUND: Survey-based studies are frequently used to describe the economic impact of multiple sclerosis (MS). However, there is no validated health resource survey available, preventing comparison of study results and meaningful conclusions regarding the efficiency of long-term treatments. OBJECTIVE: The aim of this study was to develop and validate a tablet- and paper-based MS health resource utilization survey. METHODS: We developed and validated the Multiple Sclerosis Health Resource Utilization Survey (MS-HRS), consisting of 24 cost items for paper and tablet users. Data for validation came from two large German observational studies. Survey practicability was assessed according to the response rate. Reliability was described using test-retest reliability as well as Guttman lambda. Construct validity was assessed as convergent and discriminant validity via correlations with associated patient-reported outcomes and known-group analyses. RESULTS: In total, 2207 out of 2388 (response rate: 92.4%) patients completed the survey and were included to determine psychometric properties. The test-retest reliability had an intraclass correlation coefficient of 0.828 over a course of 3 months. Convergent validity analyses showed that total costs correlated positively with increased disability (r=0.411, P<.001). For discriminant validity, correlations of total costs with the Treatment Satisfaction Questionnaire for Medication ranged from -0.006 (convenience) to -0.216 (effectiveness). The mean annual cost was €28,203 (SD €14,808) (US $39,203; SD US $20,583) with disease-modifying therapies. CONCLUSIONS: The MS-HRS is a multilingual, reliable, valid, electronically available, and easy-to-administer questionnaire providing a holistic cross-sectional and longitudinal assessment of resource utilization in patients with MS.

Correction to: Differentiating societal costs of disability worsening in multiple sclerosis.

The original version of this article unfortunately contained a mistake. The captions of Fig. 2 and Fig. 3 are mismatched.

Differentiating societal costs of disability worsening in multiple sclerosis.

BACKGROUND: In multiple sclerosis (MS), confirmed disability progression (CDP) can be either the result of progression independent of relapse activity (PIRA) or relapse-associated worsening (RAW). However, the economic effect of PIRA and RAW on societal economic costs in patients with MS is not well understood. OBJECTIVE: To determine societal economic costs of patients achieving disease activity free status (DAF) and compare them with those having PIRA and RAW events. METHODS: We used a roving EDSS score analysis to detect PIRA and RAW events with confirmation after at least 6 months. We estimated the age-, gender-, EDSS-adjusted effects of PIRA and RAW on total, direct medical, direct non-medical and indirect societal economic costs. Patients achieving DAF were assigned to as reference. RESULTS: Overall, 1959 patients were analyzed. Total mean quarterly societal economic costs including disease-modifying therapies (DMTs) were 6929€ (SD: 2886€) per patient averaged over a period of 2 years. Excluding DMTs, patients achieving DAF had total mean quarterly costs of 1703€ (SD: 2489€). PIRA caused 29% (IRR: 1.29; 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 (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. CONCLUSION: Disease progression increases societal economic costs significantly. Thus, delaying or even preventing disease progression in MS may reduce the societal economic burden of MS.