scholarly journals Health Economic Impact of Software-Assisted Brain MRI on Therapeutic Decision-Making and Outcomes of Relapsing-Remitting Multiple Sclerosis Patients—A Microsimulation Study

2021 ◽  
Vol 11 (12) ◽  
pp. 1570
Author(s):  
Diana M. Sima ◽  
Giovanni Esposito ◽  
Wim Van Hecke ◽  
Annemie Ribbens ◽  
Guy Nagels ◽  
...  
Keyword(s):  
Decision Making ◽  
Health Economic ◽  
Disease Activity ◽  
Disease Progression ◽  
Brain Volume ◽  
Volume Loss ◽  
High Efficacy ◽  
Brain Volume Loss ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis

Aim: To develop a microsimulation model to assess the potential health economic impact of software-assisted MRI in detecting disease activity or progression in relapsing-remitting multiple sclerosis (RRMS) patients. Methods: We develop a simulated decision analytical model based on a hypothetical cohort of RRMS patients to compare a baseline decision-making strategy in which only clinical evolution (relapses and disability progression) factors are used for therapy decisions in MS follow-up, with decision-making strategies involving MRI. In this context, we include comparisons with a visual radiologic assessment of lesion evolution, software-assisted lesion detection, and software-assisted brain volume loss estimation. The model simulates clinical (EDSS transitions, number of relapses) and subclinical (new lesions and brain volume loss) disease progression and activity, modulated by the efficacy profiles of different disease-modifying therapies (DMTs). The simulated decision-making process includes the possibility to escalate from a low efficacy DMT to a high efficacy DMT or to switch between high efficacy DMTs when disease activity is detected. We also consider potential error factors that may occur during decision making, such as incomplete detection of new lesions, or inexact computation of brain volume loss. Finally, differences between strategies in terms of the time spent on treatment while having undetected disease progression/activity, the impact on the patient’s quality of life, and costs associated with health status from a US perspective, are reported. Results: The average time with undetected disease progression while on low efficacy treatment is shortened significantly when using MRI, from around 3 years based on clinical criteria alone, to 2 when adding visual examination of MRI, and down to only 1 year with assistive software. Hence, faster escalation to a high efficacy DMT can be performed when MRI software is added to the radiological reading, which has positive effects in terms of health outcomes. The incremental utility shows average gains of 0.23 to 0.37 QALYs over 10 and 15 years, respectively, when using software-assisted MRI compared to clinical parameters only. Due to long-term health benefits, the average annual costs associated with health status are lower by $1500–$2200 per patient when employing MRI and assistive software. Conclusions: The health economic burden of MS is high. Using assistive MRI software to detect and quantify lesions and/or brain atrophy has a significant impact on the detection of disease activity, treatment decisions, health outcomes, utilities, and costs in patients with MS.

scholarly journals Inclusion of brain volume loss in a revised measure of ‘no evidence of disease activity’ (NEDA-4) in relapsing–remitting multiple sclerosis

2016 ◽  
Vol 22 (10) ◽  
pp. 1297-1305 ◽  
Author(s):  
Ludwig Kappos ◽  
Nicola De Stefano ◽  
Mark S Freedman ◽  
Bruce AC Cree ◽  
Ernst-Wilhelm Radue ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Brain Volume ◽  
Objective Measure ◽  
Volume Loss ◽  
Brain Volume Loss ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis ◽  
The Impact

Background: ‘No evidence of disease activity’ (NEDA), defined as absence of magnetic resonance imaging activity (T2 and/or gadolinium-enhanced T1 lesions), relapses and disability progression (‘NEDA-3’), is used as a comprehensive measure of treatment response in relapsing multiple sclerosis (RMS), but is weighted towards inflammatory activity. Accelerated brain volume loss (BVL) occurs in RMS and is an objective measure of disease worsening and progression. Objective: To assess the contribution of individual components of NEDA-3 and the impact of adding BVL to NEDA-3 (‘NEDA-4’) Methods: We analysed data pooled from two placebo-controlled phase 3 fingolimod trials in RMS and assessed NEDA-4 using different annual BVL mean rate thresholds (0.2%–1.2%). Results: At 2 years, 31.0% (217/700) of patients receiving fingolimod 0.5 mg achieved NEDA-3 versus 9.9% (71/715) on placebo (odds ratio (OR) 4.07; p < 0.0001). Adding BVL (threshold of 0.4%), the respective proportions of patients achieving NEDA-4 were 19.7% (139/706) and 5.3% (38/721; OR 4.41; p < 0.0001). NEDA-4 status favoured fingolimod across all BVL thresholds tested (OR 4.01–4.41; p < 0.0001). Conclusion: NEDA-4 has the potential to capture the impact of therapies on both inflammation and neurodegeneration, and deserves further evaluation across different compounds and in long-term studies.

EFFECT OF FINGOLIMOD VS. IFN-BETA1A ON NO EVIDENCE OF DISEASE ACTIVITY

2015 ◽  
Vol 86 (11) ◽  
pp. e4.18-e4
Author(s):  
E Silber ◽  
X Montalban ◽  
F Barkhof ◽  
B Khatri ◽  
HP Hartung ◽  
...  
Keyword(s):  
Disease Activity ◽  
Interferon Beta ◽  
Brain Volume ◽  
Disability Progression ◽  
T2 Lesions ◽  
Brain Volume Loss ◽  
Relapsing Remitting ◽  
Balanced Measure ◽  
Post Hoc ◽  
Relapsing Remitting Multiple Sclerosis

IntroductionTo compare effects of fingolimod vs. interferon beta-1a (IFN) in achieving no evidence of disease activity (NEDA-4) in patients with relapsing-remitting multiple sclerosis (RRMS) in the TRANSFORMS study. Adding Brain Volume Loss (BVL) to NEDA results in a more comprehensive and balanced measure of focal and diffuse damage.MethodsIn this post-hoc analysis, we used data from the fingolimod 0.5 mg daily (n=431) and IFN 30 µg weekly (n=435) groups. NEDA-4 was defined as absence of confirmed relapses, new/enlarging T2 lesions, 6-month confirmed disability progression (CDP) and BVL (annual percent brain volume change [PBVC] of >−0.4%). 3-month CDP and additional PBVC cut-offs representing mean BVL rates in healthy adults (0.2%), MS patients (0.6%), or accelerated BVL (1.2%) were also tested. Odds ratios (OR) were calculated for differences between fingolimod- and IFN-treated groups.ResultsSignificantly more fingolimod (n=425) than IFN-treated patients (n=418) achieved NEDA-4 status: 27.9% vs. 16.7% (OR:1.93; 95% CI: 1.36–2.73; p=0.0002). Results were similar for other PBVC cut-offs: (>–0.2%): 20.2% vs 11.5%; 1.94; 1.30–2.90, p=0.0011; (>–0.6%): 34.6% vs 20.4%; 2.06; 1.49–2.86, p<0.0001; (>–1.2%): 40.8% vs 26.4%; 1.92; 1.42–2.60; p<0.0001.ConclusionFingolimod-treated patients had twice the odds of achieving NEDA-4 status over 1 year as patients treated with IFN.

Measurement of neurofilaments improves stratification of future disease activity in early multiple sclerosis

2021 ◽  
pp. 135245852110479
Author(s):  
Tomas Uher ◽  
Eva Kubala Havrdova ◽  
Pascal Benkert ◽  
Niels Bergsland ◽  
Jan Krasensky ◽  
...  
Keyword(s):  
Disease Activity ◽  
Brain Volume ◽  
Added Value ◽  
Volume Loss ◽  
Prognostic Information ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Brain Volume Loss ◽  
Relapsing Remitting ◽  
Risk Of Disease

Background: The added value of neurofilament light chain levels in serum (sNfL) to the concept of no evidence of disease activity-3 (NEDA-3) has not yet been investigated in detail. Objective: To assess whether combination of sNfL with NEDA-3 status improves identification of patients at higher risk of disease activity during the following year. Methods: We analyzed 369 blood samples from 155 early relapsing-remitting MS patients on interferon beta-1a. We compared disease activity, including the rate of brain volume loss in subgroups defined by NEDA-3 status and high or low sNfL (> 90th or < 90th percentile). Results: In patients with disease activity (EDA-3), those with higher sNFL had higher odds of EDA-3 in the following year than those with low sNFL (86.5% vs 57.9%; OR = 4.25, 95% CI: [2.02, 8.95]; p = 0.0001) and greater whole brain volume loss during the following year (β = −0.36%; 95% CI = [−0.60, −0.13]; p = 0.002). Accordingly, NEDA-3 patients with high sNfL showed numerically higher disease activity (EDA-3) in the following year compared with those with low sNfL (57.1% vs 31.1%). Conclusion: sNfL improves the ability to identify patients at higher risk of future disease activity, beyond their NEDA-3 status. Measurement of sNfL may assist clinicians in decision-making by providing more sensitive prognostic information.

Fingolimod effect on brain volume loss independently contributes to its effect on disability

2015 ◽  
Vol 21 (7) ◽  
pp. 916-924 ◽  
Author(s):  
MP Sormani ◽  
N De Stefano ◽  
G Francis ◽  
T Sprenger ◽  
P Chin ◽  
...  
Keyword(s):  
Volume Change ◽  
Treatment Effect ◽  
Brain Volume ◽  
Surrogate Marker ◽  
Lower Percentage ◽  
Volume Loss ◽  
Disability Progression ◽  
T2 Lesions ◽  
Brain Volume Loss ◽  
Relapsing Remitting

Background: Brain volume loss occurs in patients with relapsing–remitting MS. Fingolimod reduced brain volume loss in three phase 3 studies. Objective: To evaluate whether the effect of fingolimod on disability progression was mediated by its effects on MRI lesions, relapses or brain volume loss, and the extent of this effect. Methods: Patients (992/1272; 78%) from the FTY720 Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis (FREEDOMS) study were analyzed. Month-24 percentage brain volume change, month-12 MRI-active lesions and relapse were assessed. The Prentice criteria were used to test surrogate marker validity. The proportion of treatment effect on disability progression explained by each marker was calculated. Results: Two-year disability progression was associated with active T2 lesions (OR = 1.24; p = 0.001) and more relapses during year 1 (OR = 2.90; p < 0.001) and lower percentage brain volume change over two years (OR = 0.78; p < 0.001). Treatment effect on active T2 lesions, relapses and percentage brain volume change explained 46%, 60% and 23% of the fingolimod effect on disability. Multivariate analysis showed the number of relapses during year 1 (OR = 2.62; p < 0.001) and yearly percentage brain volume change over two years (OR = 0.85; p = 0.009) were independent predictors of disability progression, together explaining 73% of fingolimod effect on disability. Conclusions: The treatment effect on relapses and, to a lesser extent, brain volume loss were both predictors of treatment effect on disability; combining these predictors better explained the effect on disability than either factor alone.

060 Association of brain volume loss and neda outcomes in patients with relapsing multiple sclerosis in the opera i and opera ii studies (ENCORE)

2018 ◽  
Vol 89 (6) ◽  
pp. A25.1-A25
Author(s):  
Anthony Traboulsee ◽  
Douglas Arnold ◽  
Eric C Klawiter ◽  
Eva Havrdova ◽  
Damian Fiore ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Brain Tissue ◽  
Repeated Measures ◽  
Brain Volume ◽  
Brain Mri ◽  
Treatment Goal ◽  
Volume Loss ◽  
T2 Lesions ◽  
Brain Volume Loss

IntroductionBrain volume loss (BVL) occurs in multiple sclerosis (MS) patients, reflecting irreversible tissue damage. No evidence of disease activity (NEDA), a composite measure assessing absence of clinical and magnetic resonance imaging (MRI) disease activity has emerged as important treatment goal in MS and may be associated with preservation of brain tissue and BVL prevention.MethodsPatients in OPERA-I/II (NCT01247324/NCT01412333) received 600 mg ocrelizumab (intravenous) very 24 weeks or 44 µg subcutaneous interferon beta-1a (IFNβ-1a) 3x-weekly for 96 weeks. Brain MRI assessments were completed at baseline and 24/48/96 Weeks. Brain volume normalised for head size was measured using SIENAX software. Percent change in whole brain volume (WBV) was determined using SIENA software, changes in cortical grey (GMV) and white (WMV) matter volumes were measured using validated, locally developed Jacobian integrator atrophy software. NEDA was defined as absence of relapses, 12-week confirmed disability progression, T1 Gd–enhancing lesions and new and/or enlarging T2-lesions. Changes from baseline in brain volume were examined in NEDA patients and those with evidence of disease activity (EDA), using the mixed-effects model for repeated measures method.ResultsThe analysis included 1520 patients (ocrelizumab-761; IFNβ-1a-759). Over 96 weeks, 569 (37%) patients [ocrelizumab-363 (48%); IFNβ-1a-206(27%); p<0.001] had NEDA. Compared with EDA patients, NEDA patients had significantly less WBV loss from baseline (30%-reduction; p<0.001). In the NEDA group, ocrelizumab patients had significantly less WBV loss (32%-reduction; p<0.001), WMV loss (34%-reduction; p=0.044) and GMV loss (30%-reduction; p<0.001) from baseline than IFNβ-1a patients. In the EDA group, ocrelizumab patients had significantly less WBV loss (11%-reduction; p=0.047) and GMV loss (21%-reduction; p<0.001) but not WMV loss (1.03%-increase; p=0.90) from baseline than IFNβ-1a patients.ConclusionThese findings highlight the importance of NEDA as treatment goal with respect to brain tissue preservation regardless of treatment choice. Ocrelizumab may confer additional benefits in NEDA patients NEDA beyond what is observed with IFNβ-1a.

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