Explore our 37 most recent scientific publications and conference presentations on real-world evidence
AI for Early Diagnosis of Progressive Multiple Sclerosis
Braune et al. (2024). Accuracy of MSBase criteria to diagnose secondary progressive multiple sclerosis in large German real-world patient cohort. Multiple Sclerosis and Related Disorders
Employing machine learning on real-world data, we tested if secondary progressive multiple sclerosis (SPMS) can be diagnosed earlier from criteria in the literature (MSBase). The results from testing a new algorithm SPMS can be diagnosed earlier than with current methods. We suggest refinements to improve diagnostic accuracy to benefit patients by earlier intervention.
Real-world Data (RWD) as Meticulous External Control Arms
Muros-Le Rouzi et al. (2024). Five-year efficacy outcomes of ocrelizumab in relapsing multiple sclerosis: A propensity-matched comparison of the OPERA studies with other disease-modifying therapies in real-world lines of treatments. Journal of Central Nervous System Disease
By carefully aligning real-world cohorts to clinical trial cohorts, we showed the effectiveness of a disease-modifying treatment for multiple sclerosis against different existing treatments. The results highlighted the treatment effects in reducing relapses and slowing disease progression.
Precision Medicine to Individualize Therapy Choices
Braune et al. (2022). PHREND®-A real-world data-driven tool supporting clinical decisions to optimize treatment in relapsing-remitting multiple sclerosis. Frontiers in Digital Health
This paper introduced PHREND®, an AI-based algorithm that predicts the effectiveness of multiple sclerosis treatments for individual unique patients based on extensive longitudinal registry data. Tailored to patient-specific characteristics, PHREND® supports doctors and patients in making informed decisions to improve outcomes, reduce relapses, and enhance quality of life.
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- Journal, Multiple Sclerosis, Real-world Evidence
Five-year efficacy outcomes of ocrelizumab in relapsing multiple sclerosis: A propensity-matched comparison of the OPERA studies with other disease-modifying therapies in real-world lines of treatments
Five-year efficacy outcomes of ocrelizumab in relapsing multiple sclerosis: A propensity-matched comparison of the OPERA studies with other disease-modifying therapies in real-world lines of treatments
Muros-Le Rouzic, E | Heer, Y | Yiu, S | Tozzi, V | Braune, S | van Hövell, P | Bergmann, A | Bernasconi, C | Model, F | Craveiro, L | & NTD study group Journal of Central Nervous System Disease (2024)
Background: Clinical trials comparing the efficacy of ocrelizumab (OCR) with other disease-modifying therapies (DMTs) other than interferon (IFN) β-1a in relapsing multiple sclerosis (RMS) are lacking. Objectives. To compare the treatment effect of OCR vs six DMTs’ (IFN β-1a, glatiramer acetate, fingolimod, dimethyl fumarate, teriflunomide, natalizumab) treatment pathways used in clinical practice by combining clinical trial and real-world data.
Methods: Patient-level data from OPERA trials and open-label extension phase, and from the German NeuroTransData (NTD) MS registry, were used to build 1:1 propensity score-matched (PSM) cohorts controlling for seven baseline covariates, including brain imaging activity. Efficacy outcomes were time to first relapse and time to 24-week confirmed disability progression over 5.5 years of follow-up. Intention-to-treat analysis using all outcome data irrespective of treatment switch was applied. Results: The analyses included 611 OPERA patients and 7141 NTD patients. We built 12 paired-matched cohorts (six for each outcome, two for each DMT) to compare efficacy of OCR in OPERA with each DMT treatment pathway in NTD. Post-matching, baseline covariates and PS were well balanced (standardized mean difference <.2 for all cohorts). Over 5.5 years, patients treated with OCR showed a statistically significant reduction in the risk of relapse (hazard ratios [HRs] .30 to .54) and disability progression (HRs .51 to .67) compared with all index therapies and their treatment switching pathways in NTD. Treatment switch and/or discontinuation occurred frequently in NTD cohorts. Conclusion: OCR demonstrates superiority in controlling relapses and disability progression in RMS compared with real-world treatment pathways over a 5.5-year period. These analyses suggest that high-efficacy DMTs and high treatment persistence are critical to achieve greatest clinical benefit in RMS.
- Journal, Migraine, Real-world Evidence
Therapeutic patterns and migraine disease burden in switchers of CGRP-targeted monoclonal antibodies–insights from the German NeuroTransData registry
Therapeutic patterns and migraine disease burden in switchers of CGRP-targeted monoclonal antibodies–insights from the German NeuroTransData registry
Hong, JB | Israel-Willner, H | Peikert, A | Schanbacher, P | Tozzi, V | Köchling, M | … & NTD Study Group. The Journal of Headache and Pain (2024)
Background. Monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway have shown good efficacy in migraine prophylaxis. However, a subset of patients does not respond to the first mAb treatment and switches among the available mAbs. The goal of this study is to characterize the switching pattern of migraine patients treated with anti-CGRP(-receptor, -R) mAbs, and to describe the headache burden of those who did not switch, switched once, and switched twice.
Methods This study used real world data from the NeuroTransData Cohort, a registry of migraine patients treated at outpatient neurology clinics across Germany. Patients who had received at least one anti-CGRP(-R) mAb were included. Headache diaries were collected at baseline and during treatment, along with quality of life measures every three months. Results were summarized for the subgroups of patients who did not switch and those with one and two switches. Results Of the 655 eligible patients, 479 did not switch, 135 switched once, 35 twice, and 6 three or more times. The ≥ 50% response rates for monthly migraine days were 64.7%, 50.7%, and 25.0% for the no switch, one switch, and two switches groups in their last treatment cycles, respectively. Quality of life measures improved for the no switch and one switch groups, but not for the two switches group. Conclusion Patients who switched among anti-CGRP(-R) mAbs during the course of their treatment still benefited overall but to a lesser extent than those who did not switch. Treatment response in patients who switched twice was markedly lower compared to the no switch and one switch subgroup.
- Digital Health, Journal, Multiple Sclerosis, Precision Medicine
- DigitalHealth1, Journal1
Accuracy of MSBase criteria to diagnose secondary progressive multiple sclerosis in large German real-world patient cohort
Accuracy of MSBase criteria to diagnose secondary progressive multiple sclerosis in large German real-world patient cohort
Braune, S | Karamasioti, E | van Hoevell, P | Bergmann, A | Skuljec, J | Siva, A | Ntd Study Group, & Pul, R. Multiple Sclerosis and Related Disorders (2024)
Background and Objectives: Accurate diagnosis of secondary progression in multiple sclerosis (MS) remains a challenge since standardized criteria are missing. In 2016, the MSBase registry presented an algorithm that enabled the diagnosis of secondary progressive multiple sclerosis (SPMS) more than three years earlier compared to diagnosis by neurologists. This work aimed to test whether this approach is equally effective in a real-world cohort of MS patients.
Methods: This longitudinal retrospective study analyzed clinical data of outpatients with MS recorded until October 2020 in the NeuroTransData registry, a Germany-wide network of 153 certified neurologists. Patient data had been captured in time during clinical visits employing a defined standardized clinical data set in the webbased NeuroTransData patient management platform DESTINY®. The time between the diagnosis of relapsing-remitting multiple sclerosis (RRMS) to SPMS onset was compared with one determined using MSBase criteria (MSBC). Group 1 consisted of patients diagnosed with SPMS during the observation period, whereas group 2 included RRMS patients who did not convert to SPMS during the observation period. Results: Of 21,281 patients with MS included in our registry, 194 and 9506 patients were allocated to groups 1 and 2, respectively. 10.3% of patients with RRMS were diagnosed with SPMS simultaneously, whereas 60.8% were diagnosed with SPMS at least 3 months earlier by treating neurologists compared to the MSBC. In group 1, the MSBC showed a low sensitivity of 32.0% and an accuracy of 61.4% but a high specificity of 89.6%. In group 2, the MSBC identified 7.8% of patients with SPMS at some point during the observation time. Moreover, test-retest variability remains a challenge since 29.4% of patients diagnosed with SPMS by treating physicians did not fulfil the MSBC at a later point in time. Discussion: These results are inconsistent with earlier SPMS diagnosis using the MSBC compared to clinical diagnosis by treating physicians. Therefore, there remains a need for an operational, structured, and validated approach to SPMS diagnosis.
- Journal, Multiple Sclerosis, Real-world Evidence
Cost and quality of life of disability progression in multiple sclerosis beyond EDSS: Impact of cognition, fatigue, and limb impairment
Cost and quality of life of disability progression in multiple sclerosis beyond EDSS: Impact of cognition, fatigue, and limb impairment
Wasem, J | Heer, Y | Karamasioti, E | Muros-Le Rouzic, E | Marcelli, G | di Maio, D | Braune, S | Kobelt, G | & Dillon, P. PharmacoEconomics – Open (2024)
Background and Objective: Understanding the socioeconomic burden of multiple sclerosis (MS) is essential to inform policymakers and payers. Real-world studies have associated increasing costs and worsening quality of life (QoL) with disability progression. This study aims to further evaluate the impact of cognition, fatigue, upper and lower limb function (ULF, LLF) impairments, and disease progression per Expanded Disability Status Scale (EDSS) level, on costs and QoL.
Methods: This was a cross-sectional cohort study including 20,988 patients from the German NeuroTransData MS registry from 2009 to 2019. QoL analyses were based on EQ-5D-5L. Cost analyses included indirect/direct medical and non-medical costs. Eight subgroups, ranging from 439 to 1812 patients were created based on presence of measures for disease progression (EDSS), cognition (Symbol Digit Modalities Test [SDMT]), fatigue (Modified Fatigue Impact 5-Item Scale [MFIS-5]), ULF (Nine-Hole Peg Test [9HPT]), and LLF (Timed 25-Foot Walk [T25FW]). Multivariable linear regression assessed the independent effect of each test’s score on QoL and costs, while adjusting for EDSS and 12 other confounders. Results: Lower QoL was associated with decreasing cognition (p < 0.001), worsening ULF (p = 0.025), and increasing fatigue (p < 0.0001); however, the negative impact of LLF worsening on QoL was not statistically significant (p = 0.54). Higher costs were associated with decreasing cognition (p < 0.001), worsening of ULF (p = 0.0058) and LLF (p = 0.049), and increasing fatigue (p < 0.0001). Each 1-scale-step worsening function of SDMT, MFIS-5, 9HPT, and T25FW scores resulted in €170, €790, €330, and €520 higher costs, respectively. Modeling disability progression based on SDMT, MFIS-5, 9HPT, and T25FW scores as an interaction with EDSS strata found associations with lower QoL and higher costs at variable EDSS ranges. Conclusionsy: Disease progression in MS measured by 9HPT, SDMT, and MFIS-5 had a significant negative impact on QoL and broad socioeconomic costs independent of EDSS. T25FW had a significant negative association with costs. Cognition, fatigue, ULF, and LLF have stronger impact on costs and QoL in patients with higher EDSS scores. Additional determinants of MS disability status, including SDMT, MFIS-5, 9HPT, and T25FW, should be considered for assessing cost effectiveness of novel therapeutics for MS.
- Conference, Multiple Sclerosis, Real-world Evidence
- Conference1
Confirmed disability improvement and progression in nonactive progressive multiple sclerosis patients in a real-world registry
Confirmed disability improvement and progression in nonactive progressive multiple sclerosis patients in a real-world registry
Watson Crystal, Jarecki, J. B | Barlev, A | Heer, Y | Braune, S | Bogdanovich, S | Stahl, N | Bergmann, A | & Kresa-Reahl, K. Multiple Sclerosis Journal (2024)
Background: Information on the natural history of disability progression/improvement in nonactive progressive multiple sclerosis (naPMS) is lacking. Real-world data from the German NeuroTransData (NTD) MS registry were used to describe the natural history of disability changes in an naPMS population. Objectives: Characterize confirmed disability improvement (CDI) and confirmed disability progression (CDP) over time in naPMS patients using the NTD registry.
Methods: NaPMS (⩾2 years without relapses and Gadolinium-enhancing lesions prior to index) patients in the registry were identified using in-/exclusion criteria from EMBOLD, a Phase 2 clinical trial of ATA188, an allogeneic Epstein-Barr virus-targeted immunotherapy in naPMS; the index date was the earliest visit with an Expanded Disability Status Scale (EDSS) after patient identification starting in 2008. Patients needed ⩾2 post-index EDSS scores during the ~2-year follow-up and were considered treated if they received disease-modifying therapy (DMT) at index or untreated if they received no DMT and had a sufficient washout period. CDI and CDP were defined as ⩾1.0-point decrease/increase from index EDSS of ⩽5.0 or ⩾0.5-point decrease/increase from index EDSS of ⩾5.5 that was confirmed at the next 6-month timepoint. Endpoints included percentages of patients with a CDI or CDP at 12, 18, and 24 months, and stratified by primary and secondary PMS (PPMS and SPMS). After study criteria were met, NTD baseline demographics were balanced to EMBOLD using propensity score weighting and the percentages of untreated naPMS patients with a CDI or CDP were calculated. Results: Based on inclusion/exclusion criteria, 719 untreated (206 PPMS, 513 SPMS) and 555 treated naPMS patients were identified. The percentages of patients with a CDI at 12, 18, and 24 months were 2.5%, 3.1%, and 3.5% for untreated naPMS (3.9%, 4.2%, and 1.9% for untreated PPMS; 2.0%, 2.7%, and 4.2% for untreated SPMS) and 3.9%, 3.4%, and 4.3%, respectively, for treated naPMS. The propensity score weighting resulted in balanced cohorts and the percentages of patients with a CDI at 12, 18, and 24 months were 1.9%, 2.2%, and 2.8%, respectively. The percentages of patients with a CDP at 12, 18, and 24 months were 11.5%, 14.7%, and 20.3%, respectively, for untreated naPMS (13.3%, 14.2%, and 18.5% for untreated PPMS; 10.8%, 14.9%, and 21.1% for untreated SPMS) and 8.4%, 15.1%, and 19.1%, respectively, for treated naPMS. After the propensity score weighting, the percentages of patients with a CDP at 12, 18, and 24 months were 15.6%, 21.0%, and 23.7%, respectively. Conclusions: This real-world study showed that the percentages of naPMS patients with a CDI were 1.9-4.3% at 6-month time intervals from 12 to 24 months for DMT-treated and untreated groups. After propensity score weighting, the percentages of untreated naPMS patients with a CDI remained <5%; CDP increased over time from 15.6% at year 1 to 23.7% at year 2.
- Conference, Digital Health, Major Depression
- Conference1
Real-World-Daten zur Wirksamkeit und Sicherheit der digitalen Gesundheitsanwendung (DiGA) edupression
Real-World-Daten zur Wirksamkeit und Sicherheit der digitalen Gesundheitsanwendung (DiGA) edupression
Preiß, M | Jarecki, J. B | Köchling, M | Rujescu-Balcu, D | & Pezawas, L. DGPPN (2024)
Einleitung/Hintergrund: Die häufig berichtete geringe Therapieadhärenz von digitalen Therapeutika (DTx) in randomisierten kontrollierten klinischen Studien hat Zweifel an der Alltagstauglichkeit von DTx in der klinischen Praxis aufkommen lassen. In den meisten Fällen sind kaum naturalistische Daten zu DTx verfügbar, so dass die Bewertung des klinischen Nutzens in der Praxis unbeantwortet bleibt.
Methoden: Aus diesem Grund wurden zwischen November 2023 und Mai 2024 über das deutsche NeuroTransData-Register naturalistische Daten zur digitalen Gesundheitsanwendung (DiGA) edupression.com® herangezogen und mit Daten der DiGA (PHQ-9, Nutzungsdaten) kombiniert analysiert. Die atientencharakteristika und Veränderungen der Depressionsschwere sowie Therapieadhärenz (mittlere wöchentliche Anzahl täglicher Stimmungstagebuch-Einträge) mittels Kaplan-Meier-Methode als Wahrscheinlichkeit für die Fortsetzung der Behandlung geschätzt. rgebnisse: Insgesamt wurden 137 Patienten mit einem mittleren Alter (SD) von 48,6 (12,2) Jahren und einem mittleren PHQ-9-Wert von 14,9 (5,3) mit edupression.com® eingeschlossen. In 27,0% der Fälle erfolgte eine Monotherapie. Die herapieadhärenz (M, 95% CI) lag nach 1 Monat bei 74,2% (67,0- 82,2) und nach 2 Monaten bei 56,2% (48,3- 65,5). Bei den 65 (47,4%) Patienten mit ausreichenden PHQ-9 Daten betrug die mittlere Veränderung des PHQ-9-Wertes (95% CI) -4,62 (-5,97 – -3,26). Bei geringerer Nutzung (< 2 wöchentlich, n=47) betrug die Veränderung des PHQ-9 -2,78 (-5,03 – -0,52) im Vergleich zu -5,32 (-6,99 – -3,65) bei stärkerer Teilnahme. Diskussion: Die naturalistischen Daten zur Anwendung von edupression.com® in Deutschland sind konsistent mit der Zulassungsstudie (eFICASY-Studie) und zeigen die Wirksamkeit und Sicherheit der DiGA im klinischen Alltag. Somit kann von einer hohen externen Validität der Zulassungsstudie und der Praxistauglichkeit der DiGA ausgegangen werden.
- Journal, Multiple Sclerosis, Real-world Evidence
Erkrankte nicht mit DiGA alleine lassen, Digitale Behandlung bei MS
Erkrankte nicht mit DiGA alleine lassen, Digitale Behandlung bei MS
Bergmann, A | Kausch, U | Köchling, M | van Hövell, P | Wolf, A. NeuroTransmitter (2023)
In einer Verlaufsbeobachtung des NTD-Netzwerkes wurde Personen mit MS eine digitale Gesundheitsanwendung verschrieben. Patientinnen und Patienten wurden zu ihrem Gebrauch der Anwendung befragt.
In einer Verlaufsbeobachtung des NTD-Netzwerkes wurde Personen mit MS eine digitale Gesundheitsanwendung verschrieben. Patientinnen und Patienten wurden zu ihrem Gebrauch der Anwendung befragt.
- Journal, Multiple Sclerosis, Real-world Evidence
The natural history of primary progressive multiple sclerosis: insights from the German NeuroTransData registry
The natural history of primary progressive multiple sclerosis: insights from the German NeuroTransData registry
Braune, S | Bluemich, S | Bruns, C | Dirks, P | Hofmann, J | Heer, Y | Muros-Le Rouzic, E | Bergmann, A | NTD Study Group //10.1186/s12883-023-03273-9 (2023)
Background: Primary progressive multiple sclerosis (PPMS) is characterised by gradual worsening of disability from symptom onset. Knowledge about the natural course of PPMS remains limited. Methods: PPMS patients from the German NeuroTransData (NTD) MS registry with data from 56 outpatient practices were employed for retrospective cross-sectional and longitudinal analyses. The cross-sectional analysis included a contemporary PPMS cohort with a documented visit within the last 2 years before index date (1 Jan 2021).
The longitudinal analysis included a disease modifying therapy (DMT)-naïve population and focused on the evolution of expanded disability status scale (EDSS) from the first available assessment at or after diagnosis within the NTD registry to index date. Outcome measures were estimated median time from first EDSS assessment to first 24-week confirmed EDSS ≥ 4 and ≥ 7. Besides EDSS change, the proportion of patients on disability pension were described over time. Results: The cross-sectional analysis included 481 PPMS patients (59.9% female, mean [standard deviation, SD] age 60.5 [11.5] years, mean [SD] EDSS 4.9 [2.1]). Estimated median time from first EDSS assessment after diagnosis to reach 24-week confirmed EDSS ≥ 4 for DMT-naïve patients was 6.9 years. Median time to EDSS ≥ 7 was 9.7 years for 25% of the population. Over a decade mean (SD) EDSS scores increased from 4.6 (2.1) to 5.7 (2.0); the proportion of patients on disability pension increased from 18.9% to 33.3%. Conclusions: This study provides first insights into the German NTD real-world cohort of PPMS patients. Findings confirm the steadily deteriorating course of PPMS accompanied by increasingly limited quality of life.
- Conference, Multiple Sclerosis, Real-world Evidence
The time course of psychological and neurological variables in multiple scleroris: insights from a 24-month real-world data collection during escalation therapy
The time course of psychological and neurological variables in multiple scleroris: insights from a 24-month real-world data collection during escalation therapy
Schanbacher, P | Jarecki, J | Braune, S | Bergmann, A | van Hövell, P | NTD Study Group ECTRIMS, P1569/145 (2023)
Introduction: Research has highlighted the cognitive symptoms in patients diagnosed with multiple sclerosis (MS). It is understudied how MS patients’ cognition develops over time and how cognition changes with MS treatment switch from a baseline medication to an escalation drug. Objective: The objective consisted in a longitudinal assessment of cognitive parameters and the exploration as a surrogate marker for treatment success after switching from basic to escalation therapy for MS patients.
Cognitive symptoms might be well-suited indicators for treatment success as they are a core deficit of the disease, appear early in the disease process, their assessment is fast and non-invasive, and they are closely associated with clinical outcomes as well as quality of life. Preserving cognitive abilities should be one of the primary goals of successful MS treatment. Methods: Longitudinal 24-month monitoring of 289 relapsing-remitting MS patients (50 patients discontinued, 86 patients lost to follow up) regarding their cognitive processing speed (measured by the symbol digit modalities test, SDMT) and brain atrophy (measured by MRT) as surrogate markers for treatment success in patients switching from basic to escalation therapy. Patients were assessed at 6, 12, and 24 months in an observational study.Results: A total of 43% switched to escalation therapy and 17% of patients received escalation therapy from the start. At baseline, 41% of patients achieved a cognitive normal range SDMT score. The percentage of patients with normal information processing speed remained relatively stable (42%, 40% and 35%) during follow-up visits at 6, 12, and 24 months, respectively. This stability of cognitive capacities indicates that the escalation therapy was effective in keeping patients’ cognitive processing speed in the norm range. The stability over the observation period also applies to other psychological parameters, such as cognitive and motor fatigue and major depression; also, patients’ disability progression scores remained relatively stable.Conclusions: Escalation therapy showed a positive outcome on almost all measured parameters. It can be concluded that switching to more effective drugs through escalation therapy may be associated with a relative stability in the clinical activity of MS (relapses), disability progression (EDSS), MRI parameters, and certain behavioral factors (especially fatigue).
- Conference, Multiple Sclerosis, Real-world Evidence
Persistence to ocrelizumab compared with other disease-modifying therapies for multiple sclerosis in the German NeuroTransData registry
Persistence to ocrelizumab compared with other disease-modifying therapies for multiple sclerosis in the German NeuroTransData registry
Braune S | Dirks P; Colloud S | Davies E | Wang Q | Heer Y | Zürcher M | Sun D. Joint ECTRIMS-ACTRIMS Meeting, poster 1231/P732 (2023)
Introduction: Ocrelizumab (OCR) is given twice a year as intravenous (IV) infusions for the treatment of multiple sclerosis (MS) and has shown higher persistence than other disease-modifying therapies (DMTs) in US claims data. Maintaining high persistence is important for controlling disease worsening and may result in more favourable outcomes. Objectives/Aims: To examine the persistence to OCR compared with other DMTs and the impact on outcomes in people withrelapsing-remitting MS (pwRRMS) from the German NeuroTransData (NTD) registry.
Methods: This retrospective cohort study of the German NTD registry included adult pwRRMS who initiated a DMTbetween January 2014 and April 2022. DMTs were grouped into injectable (interferon β-1a/1b, glatirameracetate), oral (teriflunomide, dimethyl fumarate), oral for highly active disease (oral HA; cladribine, fingolimod),other IV (natalizumab) and OCR. Date of the first observed DMT was set as the index date. Persistence wasdefined as having continuous records of a DMT group during the 2 years after the index date. Persistence wasevaluated within each group and in-group switch of DMT was allowed. Association between persistence andrelapse activity, 3-months confirmed disability progression (3mCDP) and sick leave days were assessed.Results:A total of 3,907 pwRRMS (OCR: 103; injectable: 984; oral: 581; oral HA: 2,095; other IV: 144) were included. OCRusers had the highest persistence at 2 years (93%), followed by oral HA (78%), oral (67%), other IV (67%) andinjectable (55%). Compared with OCR users, pwRRMS initiating injectable (hazard ratio [HR]: 5.02, 95% CI:3.01–8.38), oral (HR: 3.36, 95% CI: 2.02–5.60), oral HA (HR: 2.29, 95% CI: 1.36–3.86) and other IV (HR: 3.56, 95%CI: 2.05–6.19) were more likely to discontinue. Overall, adverse events (32.5%), lack of efficacy (21.2%) andpatient driven (19.7%) were the main reasons for discontinuation. Compared with non-persisters, persisters at 2years were associated with lower risk of relapse activity (rate ratio: 2.18, 95% CI: 1.98–2.39), 3mCDP (risk ratio:1.52, 95% CI: 1.28–1.77) and sick leave days (risk ratio: 1.71, 95% CI: 1.49–1.98) across all DMT groups. Similarresults were observed at 3 years.Conclusion:In a real-world setting, OCR users had higher persistence compared with those taking other DMTs over 2 and 3years, and persistence was associated with lower risk of clinical disease activity and sick leave days. Increasingpersistence is important to achieving therapeutic goals.
- Journal, Multiple Sclerosis, Real-world Evidence
The socioeconomic impact of disability progression in multiple sclerosis: A retrospective cohort study of the German NeuroTransData (NTD) registry
The socioeconomic impact of disability progression in multiple sclerosis: A retrospective cohort study of the German NeuroTransData (NTD) registry
Dillon, P | Heer, Y | Karamasioti, E | Muros-Le Rouzic, E | Marcelli, G | di Maio, D | Braune, S | Kobelt, G | & Wasem, J. Multiple Sclerosis Journal – Experimental (2023)
Background – Multiple sclerosis (MS) is a progressively debilitating neurologic disease that poses significant costs to the healthcare system and workforce. – Objective – To evaluate the impact of MS disease progression on societal costs and quality of life (QoL) using data from the German NeuroTransData (NTD) MS registry.
– Methods – Cross-sectional cohort study. The cost cohort included patients with MS disability assessed using Expanded Disability Status Scale (EDSS) in 2019 while the QoL cohort included patients assessed using EDSS and EuroQol-5 Dimension 5-Levels between 2009 and 2019. Direct and indirect medical, and non-medical resource use was quantified and costs derived from public sources. – Results – Within the QoL cohort (n = 9821), QoL worsened with increasing EDSS. Within the cost cohort (n = 7286), increasing resource use with increasing EDSS was observed. Societal costs per patient, excluding or including disease-modifying therapies, increased from €5694 or €19,315 at EDSS 0 to 3.5 to €25,419 or €36,499 at EDSS 4 to 6.5, and €52,883 or €58,576 at EDSS 7 to 9.5. In multivariate modeling, each 0.5-step increase in EDSS was significantly associated with increasing costs, and worsening QoL. – Conclusion – This study confirms the major socioeconomic burden associated with MS disability progression. From a socioeconomic perspective, delaying disability progression may benefit patients and society.
- Conference, Multiple Sclerosis, Real-world Evidence
Analysis of oral disease-modifying therapies using real-world data from the German NeuroTransData
Analysis of oral disease-modifying therapies using real-world data from the German NeuroTransData
Braune, S | Heer, Y | Jarecki, JB | Zürcher, M | DeBoer, E | Wisskirchen, C | & Biswas, M. ECTRIMS (2023)
Introduction: Ozanimod (OZA) is an oral disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS). While comparisons of OZA with other oral DMTs using clinical trial data have shown a favourable risk-benefit profile, only limited evidence is available on real-world outcomes associated with the DMTs. Objectives/Aims: To evaluate treatment discontinuation associated with OZA, dimethyl fumarate (DMF) and teriflunomide (TERI) in RRMS.
Methods: In this retrospective study, we used data from a German multiple sclerosis (MS) registry (NeuroTransData) to identify adult patients (pts) diagnosed with RRMS or an “initial manifestation of MS” (ICD-10 G35.0, G35.1) receiving an oral DMT of interest (OZA, TERI or DMF) between 20 May 2020 and 1 March 2023. Index date was defined as the start of the oral DMT. Pts diagnosed with secondary-progressive or primary-progressive MS were excluded. Eligible pts were grouped according to oral DMT received and were followed up to 12 months post-index. Demographics and clinical characteristics at index date were assessed, as was risk of treatment discontinuation, which was analysed using a Cox regression model adjusted for key covariates such as age, sex, number of prior DMTs, baseline Expanded Disability Status Scale (EDSS) score, and number of relapses 1 year prior to index. Results: The OZA cohort included 117 pts; the DMF and TERI cohorts included 309 and 214 pts, respectively. Mean exposure time was similar across cohorts (OZA: 8.3 months, DMF: 8.0 months, and TERI: 9.0 months). Patient characteristics between treatment cohorts were also similar with respect to age, EDSS score, and number of relapses 1 year pre-index. A larger proportion of OZA pts received ⩾2 prior DMTs (42% vs 27% [DMF] vs 30% [TERI]). Compared to OZA, the risk of discontinuation was significantly higher with DMF (adjusted hazard ratio [95% confidence interval]: 2.5 [1.3, 5.0], P=0.008), and numerically higher with TERI (adjusted hazard ratio [95% confidence interval]: 1.6 [0.83, 3.3], P=0.153). Conclusion: In the first year of treatment, OZA was associated with a lower risk of discontinuation than DMF, indicating a higher treatment persistence. A larger study with longer observation times is needed to validate these findings.
- Digital Health, Journal, Multiple Sclerosis, Precision Medicine, Real-world Evidence
PHREND®- a real-world data-driven rool supporting clinical decisions to optimize treatment in relapsing-remitting multiple sclerosis
PHREND®- a real-world data-driven rool supporting clinical decisions to optimize treatment in relapsing-remitting multiple sclerosis
Braune, S | Stuehler, E | Heer, Y | van Hoevell, P | Bergmann, A | & NeuroTransData Study Group Frontiers in Digital Health (2022)
Background: With increasing availability of disease-modifying therapies (DMTs), treatment decisions in relapsing-remitting multiple sclerosis (RRMS) have become complex. Data-driven algorithms based on real-world outcomes may help clinicians optimize control of disease activity in routine praxis.
Objectives: We previously introduced the PHREND® (Predictive-Healthcare-with-Real-World-Evidence-for-Neurological-Disorders) algorithm based on data from 2018 and now follow up on its robustness and utility to predict freedom of relapse and 3-months confirmed disability progression (3mCDP) during 1.5 years of clinical practice. Methods: The impact of quarterly data updates on model robustness was investigated based on the model’s C-index and credible intervals for coefficients. Model predictions were compared with results from randomized clinical trials (RCTs). Clinical relevance was evaluated by comparing outcomes of patients for whom model recommendations were followed with those choosing other treatments. Results: Model robustness improved with the addition of 1.5 years of data. Comparison with RCTs revealed differences <10% of the model-based predictions in almost all trials. Treatment with the highest-ranked (by PHREND®) or the first-or-second-highest ranked DMT led to significantly fewer relapses (p < 0.001 and p < 0.001, respectively) and 3mCDP events (p = 0.007 and p = 0.035, respectively) compared to non-recommended DMTs. – Conclusion – These results further support usefulness of PHREND® in a shared treatment-decision process between physicians and patients.
- Journal, Multiple Sclerosis, Real-world Evidence
How do patients with secondary progressive multiple sclerosis enrolled in the EXPAND randomized controlled trial compare with those seen in German clinical practice in the NeuroTransData multiple sclerosis registry?
How do patients with secondary progressive multiple sclerosis enrolled in the EXPAND randomized controlled trial compare with those seen in German clinical practice in the NeuroTransData multiple sclerosis registry?
Braune, S | Bergmann, A | Bezlyak, V | Adlard, N. Journal of Central Nervous System Disease (2022)
Background. In EXPAND (NCT01665144), a phase 3 randomized clinical trial, siponimod reduced disability progression versus placebo in patients with secondary progressive multiple sclerosis (SPMS). Aim. To understand how a real-world population with SPMS relates to that in EXPAND, we conducted a retrospective, observational cohort study using the German NeuroTransData (NTD) multiple sclerosis (MS) registry.
– Methods – The NTD MS registry is run by a Germany-wide network of physicians. Two cross-sectional analyses were performed using the NTD MS registry. The first included patients with SPMS, as recorded in the registry, and compared their characteristics between 1 January 2018 and 31 December 2018 with patients in EXPAND. The second described the characteristics of patients in the registry at the time of diagnosis of SPMS between 1 January 2010 and 31 December 2018. Results The first analysis included 773 patients: patients were older in the NTD MS registry than in EXPAND (mean age, 57.9 vs 48.0 years) and had a longer duration of SPMS (mean, 6.2 vs 3.8 years). In the NTD MS registry, median Expanded Disability Status Scale (EDSS) scores were comparable to EXPAND (6.0 versus 6.0), although fewer patients had relapses in the previous 24 months (16% vs 36% [siponimod] and 37% [placebo]). Data on gadolinium-enhancing lesions were only available for 5.8% of patients in the NTD MS registry. The second analysis included 916 patients: at the time of SPMS diagnosis, the mean age was 53.2 years and the median EDSS score was 5.0. Conclusions. The population in the NTD MS registry was older to that in EXPAND, but were similar in terms of disability. Differences likely reflect the inclusion criteria of EXPAND but also highlight that real-world populations encompass a wider range of patient characteristics.
- Conference, Multiple Sclerosis, Real-world Evidence
Ocrelizumab in patients with early-stage RRMS – results from the phase IIIb ENSEMBLE-trial and the matched real-world NTD MS registry cohort
Ocrelizumab in patients with early-stage RRMS – results from the phase IIIb ENSEMBLE-trial and the matched real-world NTD MS registry cohort
Hartung, HP | Holmey, T | Wuerfel, J | Heer, Y | Braune, S | Bergmann; A | Zuercher, M | Liu, C | Kuenzel, T | Moore, S | Vollmer, T. ECTRIMS (2022)
Background: Early treatment of multiple sclerosis (MS) with high efficacy disease-modifying therapies (DMTs) can provide long-term benefits on disease outcomes. Our understanding of ocrelizumab (OCR) effectiveness in early-stage MS is still limited. Aims: To assess treatment effectiveness of OCR in patients with early-stage relapsing-remitting MS (RRMS) from ENSEMBLE (NCT03085810) compared with commonly used first-line DMTs in a real-world setting, using the German NeuroTransData (NTD) MS registry as an external control arm.
Methods: Treatment-naive patients with early-stage RRMS (age 18–55 years; disease duration ⩽3 years; Expanded Disability Status Scale [EDSS] ⩽3.5; with ⩾1 signs of MRI activity or ⩾1 relapses in the prior 12 months) from the multicentre, open-label, single-arm Phase IIIb ENSEMBLE study, received OCR 600 mg every 24 weeks for 192 weeks. The matched NTD cohort was selected using ENSEMBLE inclusion criteria, with interferon β-1a/1b, glatiramer acetate, dimethyl fumarate and teriflunomide as comparators. NTD patients were matched to ENSEMBLE using 1:1 propensity score matching adjusted for age, EDSS score, prior relapses, baseline (BL) T1-weighted contrast-enhancing lesions (T1w-CELs) and time since first MS symptom. NTD patients had sufficient on-therapy data to assess no evidence of disease activity (NEDA)-2 (no relapses and no 24-week confirmed disability progression [CDP]) up to Week 48 and Week 72. Sensitivity analyses with varying matching factors were performed. Results: BL characteristics for ENSEMBLE (N=1,050 with sufficient data [BL MRI, Week 48 MRI, Week 72 EDSS]) and NTD (N=601) were similar (ENSEMBLE/NTD: Median age, 32.0/33.9; female, 63.4/66.7%; median duration since first MS symptom, 0.75/0.43 years; median duration since RRMS diagnosis, 0.22/0.16 years; BL EDSS score, 1.79/1.06). The odds ratio (95% CI) for ENSEMBLE vs NTD (462 vs 278 patients) for NEDA-2 was 1.68 (1.04–2.72; p=0.047) at Week 48, and 1.99 (1.29–3.07; p<0.001) at Week 72. Week 72 NEDA-2 did not change substantially when duration since first MS symptom or (T1w-CELs) were excluded from matching. NEDA-3 results (including no MRI activity) up to 48 weeks will also be presented. Conclusions: Treatment with ocrelizumab in patients with early RRMS was associated with significantly lower risk of relapses or CDP compared with first-line treatment with other DMTs in the real-world. Sensitivity analyses of NEDA-2 and NEDA-3 and its components support robustness of results.
- Conference, Migraine, Real-world Evidence
Real world study of migraine patients treated with galcanezumab or topiramate in the german NeuroTransData network
Real world study of migraine patients treated with galcanezumab or topiramate in the german NeuroTransData network
Köchling, M | Tozzi, V | Willner, H | Paddock, S | Roßnagel, F | Kestner, J | Schwerdtner, I. EAN (2022)
Background and aims: Recent approvals of calcitoningene-related-peptide (CGRP) monoclonal antibodies (mAbs) for the prophylactic treatment of migraine provide new therapeutic opportunities. We report baseline results from an ongoing real-world study aimed to improve our understanding of prescribing patterns of galcanezumab, a novel CGRP mAb launched in Germany in 2019, and topiramate, a conventional prophylactic treatment.
Methods: We collected retrospective data from a nationwide registry in Germany (NeuroTransData) including patients treated with galcanezumab or topiramate for a descriptive assessment of socio-demographic factors, clinical characteristics, patient-reported outcomes (PROs), and treatment sequences. The study included adult patients with ≥4 monthly migraine days (MMDs), required in the European galcanezumab label indication (study interval May-1-2018 to Nov-16-2021; see Figure 1 for study design/ methodology details). Results: We identified 65 patients treated with galcanezumab and 111 with topiramate. Core sociodemographic data showed that the age at diagnosis was similar in the two groups while employment status differed (Table 1). Exploratory comparisons of clinical characteristics revealed that galcanezumab-treated patients had more baseline monthly migraine days (MMDs) and monthly headache days (MHD) and were more likely to suffer from chronic migraine (CM) (Table 2). Pre-treatment assessments of PROs showed similar values between groups, but interpretation is limited due to incomplete responses. Galcanezumab was mostly used as the first (n=30) or second (n=26) CGRP mAb. Conclusion: This real-world study revealed similarities and differences between patient groups receiving galcanezumab and the conventional prophylactic treatment topiramate when including patients with ≥4 MMDs. Future studies on comparative real-world effectiveness will need to take these characteristics into account.
- Digital Health, Journal, Multiple Sclerosis
Implementation of a data control framework to ensure confidentiality, integrity, and availability of high-quality real-world data (RWD) in the NeuroTransData (NTD) registry
Implementation of a data control framework to ensure confidentiality, integrity, and availability of high-quality real-world data (RWD) in the NeuroTransData (NTD) registry
Wehrle, K | Tozzi, V | Braune, S | Roßnagel, F | Dikow, H | Paddock, S | Bergmann, A | & van Hövell, P. JAMIA open (2022)
Objective: To implement a dynamic data management and control framework that meets the multiple demands of high data quality, rigorous information technology security, and flexibility to continuously incorporate new methodology for a large disease registry. Materials and Methods: Guided by relevant sections of the COBIT framework and ISO 27001 standard, we created a data control framework supporting high-quality real-world data (RWD) studies in multiple disease areas.
We first mapped and described the entire data journey and identified potential risks for data loss or inconsistencies. Based on this map, we implemented a control framework adhering to best practices and tested its effectiveness through an analysis of random data samples. An internal strategy board was set up to regularly identify and implement potential improvements. Results: We herein describe the implementation of a data management and control framework for multiple sclerosis, one disease area in the NeuroTransData (NTD) registry that exemplifies the dynamic needs for high-quality RWD analysis. Regular manual and automated analysis of random data samples at multiple checkpoints guided the development and implementation of the framework and continue to ensure timely identification of potential threats to data accuracy. Discussion and conclusions: High-quality RWD, especially those derived from long-term disease registries, are of increasing importance from regulatory and reimbursement perspectives, requiring owners to provide data of comparable quality to clinical trials. The framework presented herein responds to the call for transparency in real-world analyses and allows doctors and patients to experience an immediate benefit of the collected data for individualized optimal care.
- Conference, Multiple Sclerosis, Real-world Evidence
Is there an impact on early initiation of DMTs in patients with RRMS in the German registry?
Is there an impact on early initiation of DMTs in patients with RRMS in the German registry?
Braune, S | Drewek, A | Bergmann, A | Schuier, M | Gandhi, K | Deren, J. ECTRIMS (2022)
Background: MS is a chronic progressive disease resulting in disability. Early intervention may help slow disease progression. Aim: To compare the characteristics and outcomes of patients who initiate disease modifying treatments (DMTs) early compared to later over a 5-year period. Methods: Data came from NeuroTransData (NTD) MS registry run by a network of Germany-wide neurologists. Study included patients initiating DMTs between Jan 1, 2009, and Oct 1, 2021.
Patient cohorts were defined based on the time of initiation of their first DMT relative to the date of RRMS diagnosis: Cohort 1 ( 12 months to 24 months to < 5 years, n=788), and Cohort 4 treatment (more than 5 years, n=1604). Results: There were no meaningful differences in age, time since symptoms manifestation, or EDSS across the cohorts at time of first DMT initiation (index). Relapse activity appeared to be a leading reason for DMT initiation with at least one relapse experienced 1-year pre-index by 43.6% patients in cohort 1 compared to 31.3%, 27.2% and 18.1% of patients in cohorts 2,3,4, respectively. Glatiramer acetate/interferons were most used in cohort 1 (74.4%) and least in cohort 4 (54.5%). The use of other DMTs, including monoclonal antibodies, increased with delayed time to DMT initiation. For cohorts 1 and 2, average (SD) annual relapse rate (ARR) was 0.4 (0.6) and 0.3 (0.6) at year 1 but declined to 0.08 (0.3) and 0.1 (0.3) by year 5, respectively. In contrast, average ARR mean (SD) was in a narrow range for cohorts 3 [0.1 (0.4)- 0.2 (0.5)] and 4 [0.05 (0.2)-0.1 (0.3)] through the study period. EDSS for patients delaying DMTs numerically worsened than those who initiated early over 5 years [e.g., mean (SD) worsening from 1.3 (1.1) at year 1 to 1.9 (1.6) at year 5 in cohort 3 compared to stable EDSS of 1.5 over 5 years in cohort 1]. EDSS results must be interpreted with caution due to high level of missingness. Conclusions: Neurologists appear to make a reasonable prognosis regarding potential changes in patients’ EDSS status over a 5-year period and whether to initiate treatment or wait and see clinical changes. A potential trade-off with the wait and see approach is that more efficacious treatments are used as initial therapy. Nevertheless, the benefit: risk of such treatments may be an important consideration along with other disease-related factors in individualizing patient treatment decisions.
- Conference, Multiple Sclerosis, Real-world Evidence
Assessing the Impacts of persistency for disease modifying therapies in a german registry for multiple sklerosis
Assessing the Impacts of persistency for disease modifying therapies in a german registry for multiple sklerosis
Braune, S | Drewek, A | Bergmann, A | Keenan, A | Gandhi, K | Schuier, M | van Deren, J | Ait-Tihyaty, M | H Le, H. ECTRIMS (2022)
Background: Multiple sclerosis (MS) is an uncurable progressive disease, with numerous disease modifying therapies (DMTs) available. Treatment persistency is an important factor for disease management. Aim: To identify, characterize, and compare outcomes of patients with high persistency (HP) and low persistency (LP).
Methods: Study data came from MS disease registry of the doctors-run German NeuroTransData(NTD) network of neurologists and psychiatrists capturing demographic, clinical history, and clinical variables during outpatient visits. Inclusion criteria were patients with RRMS, treatment naïve or 1 switch, and with one future visit after therapy start. Only patients with an index date (i.e., therapy start) after 1 January 2009 were retained.From patient distribution, HP was defined as continuous exposure time of at least two years, while LP was less than two years. Propensity Score Matching was performed on age, sex, relapses, baseline EDSS, and time since MS manifestation for 1 year pre-index. Cox regression was used to compare time to first relapse and time to 12-week confirmed disability progression (CDP). Results: In total, 2,367 patients were matched for HP and LP cohorts. The mean [standard deviation (SD), interquartile range (IQR)] for age was 38.3 (10.7; 29.9-46.4) years, 0.7 relapses in the past year (0.8; 0-1), mean baseline EDSS was 2.0 (1.5;1-3), and symptoms manifestation time was 6.6 years (sd:7.2; 0.96-10.3); 76.2% were females. Mean (SD; IQR) DMT exposure time in years was 0.78 years (0.57;0.29-1.2) for the LP cohort and 4.7 (2.2;2.9-6.2) for the HP cohort.The use of DMTs was: 49.1% on injectables, 40.5% on orals, 2.2% on infusions (excluding monoclonal antibodies) and 8.2% on monoclonal antibodies. Using Cox Regression, the hazard ratio (95% CI) on time to relapse for LP versus HP cohort was 1.4 (1.3-1.5) (Wald p value: < 0.001). For time to first CDP, it was 1.2 (1.0-1.3) (Wald p value: 0.011). Conclusion: HP had better outcomes on time to first relapse than matched LP cohort. The minor difference in CDP risk between two cohorts may be due to 2 years limited follow-up. These findings support the importance of identifying appropriate DMTs for individual patients with due consideration to their underlying disease characteristics in maintaining treatment persistency and improved outcomes.
- Conference, Multiple Sclerosis, Real-world Evidence
Behandlung der Multiplen Sklerose mit krankheitsmodifizierenden Therapien: Eine Bestandsaufnahme der Versorgungsrealität in Deutschland im Jahr 2021
Behandlung der Multiplen Sklerose mit krankheitsmodifizierenden Therapien: Eine Bestandsaufnahme der Versorgungsrealität in Deutschland im Jahr 2021
Bergmann, A | Brünner, Y | Güneli, N | Wolf, I | Roßnagel, F | Braune, S DGN (2022)
Hintergrund: Im Jahr 2021 wurden die Leitlinien der Deutschen Gesellschaft für Neurologie (DGN) überarbeitet1 und das Positionspapier der Multiple Sklerose Therapie Konsensus Gruppe (MSTKG) veröffentlicht.2 Zudem wurden neue Wirkstoffe zur Behandlung der MS zugelassen. Ziele: Ziel dieser retrospektiven Registeranalyse ist es, ein umfassendes Bild der deutschen Behandlungsrealität von MSPatienten und MS-Patientinnen mit krankheitsmodifizierenden Therapien („disease-modifying therapies,“ DMTs) im Jahr 2021 zu erhalten.
Fragestellung: Die vorliegende Arbeit untersucht die Versorgungssituation mit DMTs im Allgemeinen. Methoden: Deutschlandweit wurden die Daten von 5434 aktiven (d. h. mindestens ein Praxisbesuch) Patienten und Patientinnen mit DMT-behandelter MS aus der NeuroTransData (NTD) Registerdatenbank zwischen Januar 2021 und Dezember 2021 (Indexdatum Querschnittsanalysen 31.12.2021) analysiert. Anhand deskriptiver statistischer Methoden wurden unter anderem folgende Variablen ausgewertet: demographische Charakteristika (z. B. Alter, Alter bei Diagnose, Geschlecht), klinische Parameter (z. B. EDSS Score, Anzahl und Frequenz von Rückfällen, Krankheitsdauer), durchgeführte klinische Untersuchungen (z. B. kraniale MRT-Untersuchungen, kognitive Tests) und Arbeits- und sozioökonomischer Status. Ergebnisse: Resultate einer ersten Übersicht der deskriptiven Analyse der Patientenpopulationen sind in Tabelle 1 zusammengefasst. Schlussfolgerungen: Diese erste Übersicht der umfassenden Bestandsaufnahme von 2021 zeigt eine heterogene Behandlungssituation. Weitere Analysen innerhalb dieses Projektes werden ein differenziertes Bild der Therapieregime und möglicher leitlinienbedingter Veränderungen über die Zeit ermöglichen. Dies unterstreicht die Wichtigkeit von Registern zur Bereitstellung von aktuellen Versorgungsdaten.
- Conference, Multiple Sclerosis, Real-world Evidence
The socioeconomic impact of disability progression in multiple sclerosis: A retrospective cohort study of the German NeuroTransData (NTD) registry
The socioeconomic impact of disability progression in multiple sclerosis: A retrospective cohort study of the German NeuroTransData (NTD) registry
Dillon, P | Heer, Y | Karamasioti, E | Muros-Le Rouzic, E | Marcelli, G | di Maio, D | Braune, S | Kobelt, G | & Wasem, J. ISPOR (2022)
Objectives Multiple sclerosis (MS) has socioeconomic impacts beyond direct medical costs, including investment in assistive equipment, caregiver burden, and workforce participation. This study evaluated the broad impact of MS disease progression on societal costs using routinely collected data from the German NTD MS registry.
Methods: This was a cross-sectional cohort study of 7,286 MS patients from >60 NTD centers. Eligible patients had a visit in 2019 during which a clinician assessed MS disability using the Expanded Disability Status Scale (EDSS). A second visit during the preceding year was required to ensure adequate capture of patient characteristics including, EDSS, sociodemographics, clinical history, and healthcare utilisation. Analyses were conducted from the societal perspective including direct medical and non-medical costs, and indirect costs. Costs associated with these variables were derived from public sources. Results: Included MS patients were predominantly female (72%), Relapsing-Remitting MS patients (87%), treated with disease modifying therapies (DMTs) (77%), and a mean age of 47 years. As MS disability progressed, reflected in increasing EDSS, healthcare utilization increased. Investments in equipment showed that 15.5% required walking aids, 9.5% wheelchairs, 4.9% house modifications and 3.3% house lifts, and use increased significantly from EDSS 4 onwards. Additionally 6.1% of patients required family care and 18.9% domestic aid, which was more prevalent at higher EDSS levels. Finally, of those of employment age (n=6261), the majority (53.5%) were not employed full time. Furthermore, 9.8% had at least one-day of MS-related sick leave and 20.3% received an invalidity pension. Average total socioeconomic costs in 2019, excluding or including DMTs, increased from €5702 or €18971 at EDSS 0-3, to €25977 or €36451 at EDSS 3.5-6.5, to €53821 or €58748 at EDSS 7-9.5. Conclusions: This study confirms EDSS-related increasing socioeconomic costs with MS disease progression. From a socioeconomic perspective, delaying disability progression may have benefits to patients but also to society.
- Digital Health, Journal, Multiple Sclerosis
Development of registry data to create interactive doctor-patient platforms for personalized patient care, taking the example of the DESTINY system
Development of registry data to create interactive doctor-patient platforms for personalized patient care, taking the example of the DESTINY system
Bergmann, A | Stangel, M | Weih, M | van Hövell, P | Braune, S | Köchling, M | Roßnagel, F. Frontiers in Digital Health (2021)
“Real-world evidence (RWE)” is becoming increasingly important in order to integrate the results of randomized studies into everyday clinical practice. The data collection of RWE is usually derived from large-scale national and international registries, often driven by academic centers. We We have developed a digitalized doctor-patient platform called DESTINY (DatabasE-assiSted Therapy decIsioN support sYstem) that is utilized by NeuroTransData (NTD), a network of neurologists and psychiatrists throughout Germany.
This platform can be integrated into everyday practice and, as well as being used for scientific evaluations in healthcare research, can also serve as an individual, personalized treatment application. Its various modules allow for a timely identification of side-effects or interactions of treatments, can involve patients via the “My NTC Health Guide” portal, and can collect data of individual disease histories that are integrated into innovative algorithms, e.g., for the prediction of treatment response [currently available for multiple sclerosis (MS), with other indications in the pipeline]. Here, we describe the doctor-patient platform DESTINY for outpatient neurological practices and its contribution to improved treatment success as well as reduction of healthcare costs. Platforms like DESTINY may facilitate the goal of personalized healthcare.
- Conference, Multiple Sclerosis, Real-world Evidence
Real-world experience with ocrelizumab in patients with primary progressive multiple sclerosis: insights from the German NeuroTransData Registry
Real-world experience with ocrelizumab in patients with primary progressive multiple sclerosis: insights from the German NeuroTransData Registry
Braune, S | Bluemich, S | Bruns, C | Dirks, B | Hoffmann, J | Muros-Le Rouzic, E | Bergmann A | NTD study group ECTRIMS (2021)
Introduction: Primary progressive multiple sclerosis (PPMS) is characterized by a gradual worsening of neurological disability from disease onset and affects about 10-15% of patients diagnosed with MS. Ocrelizumab (OCR), a B-cell-selective monoclonal antibody, is the only treatment for patients with PPMS approved by the EMA in January 2018.
Objectives: In a real-world setting, to describe 1) characteristics of PPMS outpatients enrolled in the German NeuroTransData (NTD) registry along with characteristics of OCR-treated PPMS patients, and 2) initial clinical experience with OCR therapy, including adherence and persistence. Methods: Real-world data analysis using the NTD registry, a network of 66 neurology outpatient services across Germany. All adult patients included were diagnosed with PPMS by a neurologist following clinical practices. Baseline characteristics recorded from the most recent visit prior to 01.01.2021 or initiation of OCR therapy were analyzed. Initial experience with OCR was explored in patients on OCR treatment for ⩾1 year. Persistence on OCR therapy was examined as a time-to-discontinuation free function; adherence was assessed using median time intervals between infusions. Results: The analysis included 460 PPMS patients of which 82 were treated with OCR. The OCR treated patients were younger (mean age 51.5, SD 10.03 vs. 62.29, SD 11.35), had a shorter time from first PPMS symptoms (mean 8.69 years, SD 7.84 vs. 18.74, SD 10.98), and similar EDSS levels; (mean 4.44, SD 1.84 vs. 4.99, SD 2.13) compared to the overall PPMS cohort. The mean exposure time to OCR was 1.50 years (SD 0.73). During the observation period, no significant change in EDSS was noted. Persistence at 12 and 24 months was 98.7 (76/77) and 94.8% (73/77) respectively and administration of infusions followed the recommended schedule (median time interval between infusions 2-8: 5.82-6.32 months) Conclusion: This study provides first insights into a German outpatient real-world cohort of PPMS patients treated with OCR. EDSS at initiation was very similar to the Oratorio RCT population1 (mean 4.7, SD 1.2). Critical factors for achieving therapeutic goals e.g. persistence and adherence to recommended dose regimes were high. Longer observation times are needed to further expand real-world experience of OCR therapy on disability outcomes.
- Conference, Migraine, Real-world Evidence
Two years of guideline-oriented migraine therapy with Erenumab under the regulatory conditions of the healthcare system in Germany
Two years of guideline-oriented migraine therapy with Erenumab under the regulatory conditions of the healthcare system in Germany
Peikert, A | Stühler, E | Tozzi, V | Köchling, M | Israel-Willner, H | Dikow, H | Rossnagel, F | Braune, S | Bergmann, A. IHC & EHF Congress (2021)
Background/Objective: German regulatory guidelines demanded 5 (EM) or 6 (CM) failed/contraindicated firstline prophylactics before covering the costs of CGRPmABs, Valproate meanwhile was omitted. Medical guidelines recommend a significant (50%) response as a prerequisite for sustained prescription. We aimed to describe results and implications of E. treatment in neurological practices under these conditions.
Methods: The headache registry of NeuroTransData network of neurologists captures demographics, headache characteristics, comorbidities, symptom load and the use and effect of acute and preventive medication via standardized webbased data entry and smartphone app. Results: Currently (01.01.21) 5121 pts. fulfilled the ICHD-3-criteria for migraine. 435 (8,5 %) received E., 431 could be evaluated. 140 (32,5 %) had CM. 14 pts. (3,2 %) stopped therapy due to side effects, 76 (17,6 %) to lacking efficacy, 43 (9,9 %) to other reasons. The responder-rate (at least 50% reduction of migraine days) rose from 40 % after 3 up to 65% after 24 injections, 25 % of the patients had a less than 25 % response after 2 years. Conclusions: Treatment with Erenumab under the regulatory conditions in Germany was mostly well tolerated and effective. A considerable proportion of patients was treated for up to 2 years without reaching 50 % response. This indicates a good ratio between tolerability and effectiveness in the evaluated sample of therapy resistant migraine patients.
- Journal, Multiple Sclerosis, Precision Medicine
Estimation and validation of ratio-based conditional average treatment effects using observational data
Estimation and validation of ratio-based conditional average treatment effects using observational data
Yadlowsky, S | Pellegrini, F | Lionetto, F | Braune, S | & Tian, L. Journal of the American Statistical Association (2021)
While sample sizes in randomized clinical trials are large enough to estimate the average treatment effect well, they are often insufficient for estimation of treatment-covariate interactions critical to studying data-driven precision medicine. Observational data from real world practice may play an important role in alleviating this problem.
One common approach in trials is to predict the outcome of interest with separate regression models in each treatment arm, and estimate the treatment effect based on the contrast of the predictions. Unfortunately, this simple approach may induce spurious treatment-covariate interaction in observational studies when the regression model is misspecified. Motivated by the need of modeling the number of relapses in multiple sclerosis (MS) patients, where the ratio of relapse rates is a natural choice of the treatment effect, we propose to estimate the conditional average treatment effect (CATE) as the ratio of expected potential outcomes, and derive a doubly robust estimator of this CATE in a semiparametric model of treatment-covariate interactions. We also provide a validation procedure to check the quality of the estimator on an independent sample. We conduct simulations to demonstrate the finite sample performance of the proposed methods, and illustrate their advantages on real data by examining the treatment effect of dimethyl fumarate compared to teriflunomide in MS patients.
- Conference, Multiple Sclerosis, Real-world Evidence
Real-world experience with Ocrelizumab in the German NeuroTransData registry
Real-world experience with Ocrelizumab in the German NeuroTransData registry
Braune, S | Heer Y | Tozzi V | van Hoevell P | Muros-Le Rouzic E | Dirks P | Bergmann A | NTD Study Group ECTRIMS (2020)
Background: Ocrelizumab (OCR) is approved for the treatment of relapsing and primary progressive forms of multiple sclerosis (MS). Objectives: In a real-world setting, to describe 1) baseline characteristics of patients with MS treated with OCR, 2) treatment pathway across lines of therapy up to initiation of OCR, and 3) initial clinical experience.
Methods: This analysis included adult patients with MS from the German NeuroTransData (NTD) Registry, a network of 66 neurology outpatient services across Germany. Patients were treated with OCR between January 2018 and January 2020. Descriptive statistics were used to analyze baseline patient characteristics recorded within 3 months prior to or at time of OCR initiation. Occurrence of relapse was analyzed in relapse-remitting MS (RRMS) patients with ⩾3 months follow-up data from OCR initiation. Results: As of January 2020, the NTD registry included 439 patients treated with OCR, including 352 patients with RRMS, 35 with relapsing secondary progressive MS (rSPMS), and 52 with primary progressive MS (PPMS). Median age at OCR initiation varied from 41.7 years, 54.5 years, to 52.5 years in patients with RRMS, rSPMS, and PPMS, respectively. Most RRMS and rSPMS patients were female (64.8% and 54.3%) compared to PPMS patients (46.2%). Median disease duration from symptom onset up to OCR initiation was longer in rSPMS patients (14.9 years) than in RRMS (10.8 years) and PPMS (5.7 years). Median EDSS at OCR start was 2.5, 6.0, and 4.0 in the RRMS, rSPMS, and PPMS cohorts, respectively. OCR was initiated as first disease modifying therapy (DMT) therapy in 12.2%, 11.4%, and 71.2% of RRMS, rSPMS, and PPMS patients, respectively. 258 RRMS patients directly switched from another DMT, primarily from fingolimod (23.3%) and natalizumab (19.8%). 319 patients with RRMS had ⩾3 months follow-up during OCR exposure; of these, 283 remained relapse free (88.7%; 95% CI 84.9, 91.8) within a median follow-up time of 1 year (Q1-Q3, 0.6-1.3 years). Annualized relapse rate was 0.13 (95 % CI 0.09, 0.16). Conclusions: In this German outpatient real world cohort, RRMS and rSPMS patients treated with OCR, on average had a disease duration ⩾10 years and already reached a moderate to severe disability status. Most patients received previous DMT and OCR was initiated most frequently as second line treatment. Although PPMS patients showed a shorter disease duration, the disability status was relatively severe. Only about one third of patients received previous DMT.
- Conference, Multiple Sclerosis, Real-world Evidence
Effectiveness of peginterferon beta-1a versus non-pegylated interferons and glatiramer acetate in a real-world setting using propensity score matching
Effectiveness of peginterferon beta-1a versus non-pegylated interferons and glatiramer acetate in a real-world setting using propensity score matching
Braune, S | Bergmann A | Rossnagel, F | Taipale, F | Pellegrini, F | Koster, T | Rehberg-Weber, K ECTRIMS (2020)
Background: Peginterferon (pegIFN) beta-1a with a prolonged half-life and increased systemic exposure was developed for the treatment (tx) of relapsing-remitting multiple sclerosis (RRMS) resulting in less frequent dosing intervals without attenuating the biological or pharmacodynamic properties associated with existing IFN treatments. Real-world data with pegIFN beta-1a in clinical practice are limited.
NeuroTransData GmbH (NTD) is a Germany-wide network of neurologists and psychiatrists. The NTD MS registry is a database capturing demographic, clinical history, and clinical variables from MS patients in a real-world setting. Objectives: To compare pegIFN beta-1a populations with populations using the following injectables: SC IFN beta-1a, IM IFN beta-1a, SC IFN beta-1b, glatiramer acetate (GA). Methods: NTD registry data from adult patients with RRMS who initiated tx no earlier than 2014, had ⩾12 months of tx exposure, and ⩾1 EDSS measurement or a relapse after index therapy initiation were retrospectively analyzed. Primary endpoints were annualized relapse rate (ARR) and time to first relapse. The secondary endpoint was time to confirmed disability progression (CDP). Patient characteristics between treatment groups were compared using propensity-score matching (PSM). Results: In total, 175 pegIFN beta-1a patients, 308 from the IFN group (SC IFN beta-1a, IM IFN beta-1a, SC IFN beta-1b), and 287 GA patients were included in the analysis set. Mean tx duration was 2.5, 2.7, and 2.4 years, respectively. After PSM, no difference was found in the ARR and time to relapse between pegIFN beta-1a patients and patients from the IFN group (estimated ARR ratio 1.18; 95% CI 0.72, 1.94; p= 0.5047; relapse hazard ratio [HR] 1.14; 95% CI 0.71, 1.84; p=0.5790) or the GA group (estimated ARR ratio 0.74; 95% CI 0.45, 1.24; p=0.2608; relapse HR 0.76; 95% CI 0.47, 1.25; p=0.2813). For time to CDP, a significantly higher estimated treatment effect in favor of pegIFN beta-1a was found compared to both, the IFN (CDP HR 0.43; 95% CI 0.21, 0.89; p=0.0234) and the GA group (CDP HR 0.46; 95% CI 0.22, 0.97; p=0.0425). Conclusions: Statistically significant superiority of pegIFN beta-1a was demonstrated for time to CDP. However, the current analysis is limited by small sample sizes and follow-up time. Updated results with larger sample sizes and longer follow-up time will be presented in order to assess if superiority of pegIFN beta-1a in other endpoints can be supported by statistical evidence.
- Conference, Migraine, Real-world Evidence
Behandlung von Migränepatienten mit Erenumab unter den Versorgungsbedingungen in Deutschland: Ergebnisse aus der NTD Kopfschmerz- und Migränedatenbank
Behandlung von Migränepatienten mit Erenumab unter den Versorgungsbedingungen in Deutschland: Ergebnisse aus der NTD Kopfschmerz- und Migränedatenbank
Peikert, A | Köchling M | Tozzi V | Dikow H | Rossnagel F | Schnabel S | Bergmann A | Braune S | NTD study group DGN (2020)
- Conference, Migraine, Real-world Evidence
First insights in real-world effectiveness of erenumab in chronic migraine patients with high burden of disease in Germany from the NTD headache and migraine registry
First insights in real-world effectiveness of erenumab in chronic migraine patients with high burden of disease in Germany from the NTD headache and migraine registry
Peikert, A | Köchling, M | Tozzi, V | Dikow, H | Rossnagel, F | Schnabel, S | Braune, S | Bergmann, A. AAN (2020)
Objective: Evaluation of patient characteristics and clinical effectiveness of erenumab in real-world care within the framework of German regulatory guidelines Background: German regulatory guidelines require 5 (episodic migraine) or 6 (chronic migraine) failed or contraindicated prophylactic treatments in migraine patients before erenumab is covered by public health insurances. Clinical effectiveness of erenumab in a chronic headache population with a high burden of disease und comorbidities is unknown.
Design/Methods: The headache registry of the German NeuroTransData (NTD) doctors network was started in Oktober 2017 capturing demographics, headache days, use and effect of acute medication and patient-related outcomes via standardized web-based data entry and NTD patient smartphone app. Diagnostic assessment is based on ICHD-3 criteria. Results: Currently (09 22 19), 3607 migraine patients are documented (83.3% females). 4.3% use non-drug prophylaxis, 24.3% established prophylaxis drugs and 5.5% CGRP-effective prophylaxis with erenumab and others. Erenumab was initiated with 70mg in 96% of patients, with 28% being switched to 140mg within 7months. 8.3% were discontinued due to lack of efficacy, 2.2% due to adverse events within the first 10months of follow-up. In 75% erenumab was the only prophylaxis, in 25% in combiation with others. More than 50% of patients achieved at least a 50% reduction of migraine days within 3 months. Response was independent of the number of unsuccessful previous treatments. Conclusions: The results from the NTD headache registry provide first insights into the effectiveness of erenumab in real-world care prescribed within the guidelines for economic use in Germany. Erenumab is very well tolerated and achieves a responder rate >50% in patients with chronic high burden of disease and a history of up to 6 failed or contrainidicated prophylactic treatments. The NTD headache registry will enable more deeper insights into the care of migraine patients and treatment effectiveness as more data accumulate over time.
- Journal, Multiple Sclerosis, Precision Medicine, Real-world Evidence
Framework for personalized prediction of treatment response in relapsing remitting multiple sclerosis
Framework for personalized prediction of treatment response in relapsing remitting multiple sclerosis
Stühler, E | Braune, S | Lionetto, F | Heer, Y | Jules, E | Westermann, C | … & NeuroTransData Study Group. BMC Medical Research Methodology (2020)
Background – Personalized healthcare promises to successfully advance the treatment of heterogeneous neurological disorders such as relapsing remitting multiple sclerosis by addressing the caveats of traditional healthcare. This study presents a framework for personalized prediction of treatment response based on real-world data from the NeuroTransData network.
– Methods – A framework for personalized prediction of response to various treatments currently available for relapsing remitting multiple sclerosis patients was proposed. Two indicators of therapy effectiveness were used: number of relapses, and confirmed disability progression. The following steps were performed: (1) Data preprocessing and selection of predictors according to quality and inclusion criteria; (2) Implementation of hierarchical Bayesian generalized linear models for estimating treatment response; (3) Validation of the resulting predictive models based on several performance measures and routines, together with additional analyses that focus on evaluating the usability in clinical practice, such as comparing predicted treatment response with the empirically observed course of multiple sclerosis for different adherence profiles. – Results – The results revealed that the predictive models provide robust and accurate predictions and generalize to new patients and clinical sites. Three different out-of-sample validation schemes (10-fold cross-validation, leave-one-site-out cross-validation, and excluding a test set) were employed to assess generalizability based on three different statistical performance measures (mean squared error, Harrell’s concordance statistic, and negative log-likelihood). Sensitivity to different choices of the priors, to the characteristics of the underlying patient population, and to the sample size, was assessed. Finally, it was shown that model predictions are clinically meaningful. – Conclusions – Applying personalized predictive models in relapsing remitting multiple sclerosis patients is still new territory that is rapidly evolving and has many challenges. The proposed framework addresses the following challenges: robustness and accuracy of the predictions, generalizability to new patients and clinical sites and comparability of the predicted effectiveness of different therapies. The methodological and clinical soundness of the results builds the basis for a future support of patients and doctors when the current treatment is not generating the desired effect and they are considering a therapy switch.
- Conference, Multiple Sclerosis, Precision Medicine
PHREND©: External validation of model to predict individual efficacy of disease modifying therapies (DMT) in relapsing-remitting multiple sclerosis (RRMS)
PHREND©: External validation of model to predict individual efficacy of disease modifying therapies (DMT) in relapsing-remitting multiple sclerosis (RRMS)
Braune, S | van Hövell, P | Drewek, A | Stühler, E | Bergmann, A. ECTRIMS (2019)
Background: Based on real-world data of the NeuroTransData (NTD) MS registry a mathematical model was developed based on generalized linear models and Bayesian inference, which calculates the individual probabilities to achieve freedom of relapse activity and of 3-month-confirmed-EDSS-progression (3mCEP) for a single patient predictively from 2 to 4 years for almost all DMTs available. Results of internal validation showing good results for discrimination and accuracy have already been communicated.
Here, first results of external validation are shown. External cohort data: Published results of active treatment arms of the clinical trials CONFIRM (dimethylfumarate, glatirameracetate), DEFINE (dimethylfumarate), REGARD (interferon-ß, glatirameracetate), TRANSFORMS (interferon-ß, fingolimod). Statistical methods: For each study population a cohort in the NTD MS registry was identified with matching clinical and demographic characteristics. Annualized relapse rates and probabilities of the PHREND (Predictive Healthcare with Real-World Evidence for Neurological Disorders) algorithm to achieve freedom of relapse activity and 3mCEP were compared with study result. Results: There was a high consistency between the PHREND algorithm and the clinical study results for both outcome parameters. The predictive outcome probabilities of PHREND closely matched the results from 4 clinical studies and seven active treatments. This positive validation of PHREND by external data further underlines validity and accuracy of this model. Additional validation projects are in progress.
- Conference, Digital Health, Migraine, Precision Medicine
Therapieoptimierung bei Migränepatienten
Therapieoptimierung bei Migränepatienten
Peikert, A | Körwer, M | Tozzi, V | Dikow, H | Roßnagel, F | Schnabel, S | Braune, S. Deutscher Schmerzkongress 2019 (2019)
Hintergrund: Trotz der Awareness Kampagnen nach Einführung der Triptane bzw. nach Abgrenzung des Krankheitsbildes der CM und Zulassung von Botulinumtoxin sind Kopfschmerz- und Migränepatienten weiterhin IT-Strukturen. Nach Implementierung des Terapieoptimierungsmoduls werden die Zahl der Interventionen sowie deren Erfolg evaluiert. Erste Ergebnisse werden im Oktober erwartet. europa- und weltweit unterdiagnostiziert und unzureichend behandelt (1, 2).
Sie sind häufg signifkant beeinträchtigt hinsichtlich ihrer Lebensqualität und erzeugen hohe Gesundheitskosten (3, 4). Ziele: Implementierung eines Terapieoptimierungsmoduls zur fortlaufenden Beurteilung der Behandlungsqualität und Stabilisierung des Behandlungserfolgs bei Migränepatienten auf der Basis eines bestehenden interaktiven Kopfschmerz- und Migräneregisters. Methodik: Das Ärztenetzwerk NeuroTransData NTD betreibt seit mehr als 10 Jahren Register für neurologische und psychiatrische Erkrankungen. Seit Ende 2017 werden während klinischer Visiten standardisiert Parameter zu Kopfschmerz- und Migränepatienten elektronisch erfasst. Die Patienten dokumentieren zudem selbst digital via App. Die gesetzlichen Vorgaben des Datenschutzes, insbesondere BDSG und EU-DSGVO, werden durch ein geeignetes Einwilligungs- und Verschlüsselungsverfahren gewährleistet. Das Datenerfassungsprotokoll wurde von den Landesärztekammern Bayern und Nordrhein positiv bewertet. Die im Verlauf erfassten Daten beinhalten demographische und klinische Informationen wie Kopfschmerztage und deren Charakteristika, die Einnahme von Akutmedikation und Prophylaktika sowie deren Efekt, nicht-medikamentöse Terapien, Begleiterkrankungen und Teilhabeeinschränkung. Weiterhin werden patientenbezogene Beurteilungen zur Lebensqualität und psychometrische Daten erfasst. Die fortlaufende diagnostische Einschätzung erfolgt durch die Ärzte nach den Kriterien des ICHD-3 (5). Zur Beurteilung der Behandlungsqualität und Terapieoptimierung werden Verlaufsbeobachtungen von Kopfschmerzlast, Gebrauch an Akutmedikation, das Ausmaß von Freizeit- und Arbeitsunfähigkeit, psychische Begleitsymptome sowie die Bewertung der Lebensqualität herangezogen. In Abhängigkeit vom Ausmaß der Abweichungen kommt ein abgestufes Reaktionssystem von zusätzlicher Telefonberatung bis zur Vereinbarung von zusätzlichen Gesprächsterminen oder medikamentösen bzw. nichtmedikamentösen Interventionen zur Anwendung. Erste Ergebnisse und Ausblick: Aktuell sind insgesamt 3193 Migräne-Patienten dokumentiert (83% Frauen). Insgesamt 10% haben eine CM. Nach den Empfehlungen von (6) erhalten aktuell 4,2% eine nichtmedikamentöse Prophylaxe, 24,3% eine medikamentöse Prophylaxe der 1. Wahl, zudem 3,4% CGRP-wirksame Prophylaktika. Die NTD PatientenmanagementPlattform für Patienten mit chronischen Kopfschmerzen verbessert die Erfassung multidimensionaler Parameter und den bilateralen Informationsaustauch zwischen Arzt und Patient auf der Basis langjährig erprobter.
- Conference, Multiple Sclerosis, Precision Medicine, Real-world Evidence
Model (PHREND) for personalized prediction of treatment response in relapsing remitting multiple sclerosis (RRMS)
Model (PHREND) for personalized prediction of treatment response in relapsing remitting multiple sclerosis (RRMS)
Stühler, E | Lionetto, F | Heer, Y | Tozzi, V | Kassraian-Fard, P | Jules, E | van Hövell, P | Braune, S | Bergmann, A. SFCNS (2019)
Aims: In multiple sclerosis (MS), due to the high complexity and using the mean squared error (MSE), log-likelihood, and Harrell’s concordance statistic (C-Index). Results: The results of the analysis revealed that predictive models provide robust and accurate predictions and generalize to new patients and clinical sites. The output of PHREND is an independent recommendation for the therapy that is statistically most likely to succeed for each individual patient, presented in a transparent and easy-to-understand way.
Conclusion: Applying personalized predictive models in RRMS patients is still new territory that is rapidly evolving and has many challenges. The proposed framework addresses the following challenges: robustness and accuracy of the predictions, generalizability to new patients and clinical sites, and comparability of the predicted effectiveness of different therapies. Nevertheless, we present the PHREND App already implemented in German doctors’ offices and we plan to expand our model to several other neurological disorders. uncertainty of disease progression, it currently takes long time to find an appropriate therapy for an MS patient and currently the treatment decision depends on a significant portion of intuition. Our solution to support relapsing remitting multiple sclerosis (RRMS) patients and their doctors during this difficult journey is to distil the large amounts of available data into meaningful and relevant decision-making information as efficiently as possible. Methods: This study employed clinical real-world data recorded in the NTD MS registry, a Germany-wide network of physicians in the fields of neurology and psychiatry founded in 2008. The registry includes about 25.000 patients with MS, which represents about 15% of all MS patients in Germany, with an average of observation period of 8,7 years. The PHREND App contains a data-driven mathematical regression model to predict MS disorder progression for individuals based on different therapies, taking into account two indicators of therapy effectiveness: number of relapses, and confirmed disability progression. We employed hierarchical generalized linear models (GLM) for both indicators of treatment response, with model parameters depending on patient’s profile and treatment. Additionally we implemented cross validation and quality of predictions assessment.
- Conference, Multiple Sclerosis, Precision Medicine, Real-world Evidence
Delayed-release dimethyl rumarate demonstrated no evidence of difference in clinical outcomes versus fingolimod in patients With RRMS: Pairwise propensity-matched comparative effectiveness analyses of the German NeuroTransData registry
Delayed-release dimethyl rumarate demonstrated no evidence of difference in clinical outcomes versus fingolimod in patients With RRMS: Pairwise propensity-matched comparative effectiveness analyses of the German NeuroTransData registry
Braune, S | Grimm, S | van Hövell, P | Freudensprung, U | Hyde, R | Bergmann, A. AAN Meeting (2018)
- Journal, Multiple Sclerosis, Real-world Evidence
Comparative effectiveness of delayed-release dimethyl fumarate versus interferon, glatiramer acetate, teriflunomide, or fingolimod: results from the German NeuroTransData registry
Comparative effectiveness of delayed-release dimethyl fumarate versus interferon, glatiramer acetate, teriflunomide, or fingolimod: results from the German NeuroTransData registry
Braune, S | Grimm, S | van Hövell, P | Freudensprung, U | Pellegrini, F | Hyde, R | Bergmann, A | & NTD Study Group Journal of Neurology (2018)
Background – Comparative effectiveness (CE) research allows real-world treatment comparisons using outcome measurements important to physicians/patients. This German NeuroTransData registry-based analysis compared delayed-release dimethyl fumarate (DMF) effectiveness with interferons (IFN), glatiramer acetate (GA), teriflunomide (TERI), or fingolimod (FTY) in patients with relapsing–remitting multiple sclerosis (RRMS) using propensity score matching (PSM).
– Methods – Data from registry patients aged ≥ 18 years with RRMS, ≥ 1 relapse, and Expanded Disability Status Scale (EDSS) assessment(s) after index therapy initiation underwent 1:1 PSM to match DMF with comparator populations baseline characteristics. Primary outcome measurement was time to first relapse (TTFR). Secondary outcome measurements included annualised relapse rate (ARR), proportion of patients relapse free at 12 and 24 months, time to index therapy discontinuation (TTD), and reasons for discontinuation. Exploratory analyses included time to 3- and 6-month EDSS confirmed disability progression (CDP). Non-pairwise censoring was the primary analysis method; pairwise censoring was the main sensitivity analysis method. Findings. Post-matched cohorts were well-balanced. By non-pairwise censoring, TTFR and ARR were significantly lower in DMF populations versus matched IFN, GA, and TERI, but there was no evidence of difference between DMF and FTY. TTD was similar between DMF and IFN, GA, and TERI, but significantly shorter versus FTY. Time to CDP generally showed no evidence of difference between DMF and comparator populations. Pairwise censored analysis results confirmed the non-pairwise censoring results. Interpretation. These results support previous CE studies in demonstrating relative improvement in real-world effectiveness with DMF versus first-line agents IFN, GA, and TERI, and similar effectiveness versus FTY.
- Conference, Multiple Sclerosis, Real-world Evidence
Characteristics of MS patients treated with PR-fampridine in a real-world setting based on the NeuroTransData network in Germany
Characteristics of MS patients treated with PR-fampridine in a real-world setting based on the NeuroTransData network in Germany
Braune, S | Grimm, S | van Hövell, P | Heer, Y; Meergans, M | Hyde, R | Bergmann, A. ECTRIMS (2018)
Introduction: During the past 7 years, real-world data (RWD) of fampridine (FAM) have accrued and may inform on patients characteristics, drug persistence, effectiveness and PROs in the post-approval setting. NeuroTransData (NTD) is a German network of office-based neurologists documenting in-depth practice based data for multiple sclerosis (MS) patients and constitutes the first multicenter RWD study for FAM.
Objectives: The objectives of this study were to characterize patients exposed to FAM and investigate FAM-persistence, including predictors. Longitudinal analyses were conducted to describe the clinical course, including expanded disability status scale (EDSS) and EQ-5D, and compare FAM responders with non-responders. Methods: Eligibility of patients was based on the availability of baseline data (e.g. MS subtype, background DMT, EDSS and FAM exposure). Baseline characteristics were described for the whole cohort as well as for responders (patients with ≥ 3 months exposure to FAM) and non-responders (< 3 months exposure). A univariate Cox regression was performed to assess the influence of potential baseline predictors on FAM discontinuation. Results: As of 1 April 2018, 1159 patients (MS subtypes: 58.8% RRMS, 31.7% SPMS, 9.6% PPMS) were exposed to FAM in 63 documenting NTD centers. In this cohort, mean (SD) time to first MS symptoms was 15.9 (10.0) years and median (IQR) FAM exposure was 17.35 (2.07, 45.83) months. At FAM initiation, 29.2% of patients were receiving interferon treatment, 13.8% oral DMT, 7.6% high efficacy DMT, and 49.4% no DMT. 820 (70.8%) patients were classified as responders. At FAM initiation, mean (SD) Multiple Sclerosis Severity Score (MSSS) was 0.67 (4.95) in responders and 1.78 (20.34) in non-responders; mean (SD) EDSS was 4.86 (1.41) in responders and 4.80 (1.48) in non-responders; and 64.0% of responders and 67.3% of non-responders had physiotherapy. Based on 1100 patients with available data, a prediction model for FAM discontinuation due to adverse events or lack of effectiveness found that response to FAM was independent of baseline disease characteristics. Conclusions: In this study of FAM patients in a real-world setting, the observed subjective response rate, based on persistence on therapy beyond 3 months, was 71%. FAM discontinuation was not strongly associated with baseline disease characteristics, thus FAM has the potential to provide benefits across a broad range of MS populations.
- Conference, Multiple Sclerosis, Precision Medicine
PHREND®: Kohorten-basierte externe Validierung der Prädiktion des Verlaufes der schubförmig remittierenden Multiplen Sklerose (RRMS)
PHREND®: Kohorten-basierte externe Validierung der Prädiktion des Verlaufes der schubförmig remittierenden Multiplen Sklerose (RRMS)
Braune, S | van Hövell, P | Grimm, S | Drewek, A | Stühler, E | Bergmann, A. DGN (2018)
- Conference, Multiple Sclerosis, Precision Medicine
Supporting personalized treatment decisions in relapsing remitting multiple sclerosis (RRMS)
Supporting personalized treatment decisions in relapsing remitting multiple sclerosis (RRMS)
Braune, S | van Hövell, P | Grimm, S | Drewek, A | Stühler, E | Ziemssen, T | Bergmann, A. AAN (2018)
- Conference, Multiple Sclerosis, Precision Medicine, Real-world Evidence
Model (PHREND) for personalized prediction of treatment response in relapsing remitting multiple sclerosis (RRMS)
Model (PHREND) for personalized prediction of treatment response in relapsing remitting multiple sclerosis (RRMS)
Braune, S | van Hövell P | Stühler, E | Drewe, A | Grimm, S | Ziemssen, T | Bergmann, A | NeuroTransData Study Group. ACTRIMS (2017)
Background: Therapeutic decisions in RRMS have become complex as many drugs with different benefit/risk ratios are available. Method: Development of PHREND (Predictive Healthcare with Real world Evidence in Neurological Disorders) is based on 3320 therapy cycles of adult RRMS patients with
Background: Therapeutic decisions in RRMS have become complex as many drugs with different benefit/risk ratios are available. Method: Development of PHREND (Predictive Healthcare with Real world Evidence in Neurological Disorders) is based on 3320 therapy cycles of adult RRMS patients with