Objective: To integrate long-term measures of disease-modifying drug efficacy and risk to guide selection of first-line treatment of multiple sclerosis. Methods: We created a Markov decision model to evaluate disability worsening and progressive multifocal leukoencephalopathy (PML) risk in patients receiving natalizumab (NTZ), fingolimod (FGL), or glatiramer acetate (GA) over 30 years. Leveraging publicly available data, we integrated treatment utility, disability worsening, and risk of PML into quality-adjusted life-years (QALYs). We performed sensitivity analyses varying PML risk, mortality and morbidity, and relative risk of disease worsening across clinically relevant ranges. Results: Over the entire reported range of NTZ-associated PML risk, NTZ as first-line therapy is predicted to provide a greater net benefit (15.06 QALYs) than FGL (13.99 QALYs) or GA (12.71 QALYs) treatment over 30 years, after accounting for loss of QALYs due to PML or death (resulting from all causes). NTZ treatment is associated with delayed worsening to an Expanded Disability Status Scale score ≥6.0 vs FGL or GA (22.7, 17.0, and 12.4 years, respectively). Compared to untreated patients, NTZ-treated patients have a greater relative risk of death in the early years of treatment that varies according to PML risk profile. Conclusions: NTZ as a first-line treatment is associated with the highest net benefit across full ranges of PML risk, mortality, and morbidity compared to FGL or GA. Integrated modeling of long-term treatment risks and benefits informs stratified clinical decision-making and can support patient counseling on selection of first-line treatment options.

Selection of first-line therapy in multiple sclerosis using risk-benefit decision analysis

https://www.neurologic.theclinics.com/article/S0733-8619(16)30017-2/pdf

Neurotherapeutic Strategies for Multiple Sclerosis

Arnold DL, Calabresi PA, Kieseier BC, Sheikh SI, Deykin A, Zhu Y, Liu S, You X, Sperling B, Hung S. Effect of peg-interferon beta-1a on MRI measures and achieving no evidence of disease activity: results from a randomized controlled trial in relapsing-remitting multiple sclerosis. BMC Neurol. 2014 Dec 31;14(1):1058. Y Y Y N Exclude ADVANCE Combined outcome of relapse and disability progression Brinar V, Arnold DL, Cohen J, Coles AJ, Fox EJ, Hartung HP, et al. Alemtuzumab improves expanded disability status scale (EDSS) via effects on functional systems: CARE-MS II. Mult Scler 2013;1):283-284. N Exclude

Medicines Used for Multiple Sclerosis – A Health Technology Assessment

Using evidence from short-term randomized controlled trials, decision-analytic models project costs, risks and benefits of disease-modifying therapies (DMTs) for multiple sclerosis (MS). Such trial-informed models lack the breadth needed to generalize to clinical practice or policy due to limitations: lack of DMT switching/discontinuation, limited head-to-head DMT comparisons and efficacy, not effectiveness, designs. We present an illustrative example that incorporates treatment switching and discontinuation by estimating the cost-effectiveness (value) of first-line natalizumab versus second-line natalizumab treatment for relapsing-remitting MS patients negative for anti-JC virus antibodies. Treating JC virus-negative relapsing-remitting MS patients with natalizumab as first-line provided better value compared with second-line. Decision-makers should consider this evidence for treatment step-edit policies through modeling scenarios closer to clinical practice.

https://www.tandfonline.com/doi/pdf/10.1586/14737167.2015.1081060

Incorporating real-world clinical practice in multiple sclerosis economic evaluations.

PurposeTo analyse the evolution of impact on the healthcare expenditure of first and second line treatments for relapsing-remitting multiple sclerosis (RRMS) in Italy.MethodsAn economic model was d...

Evolution of the Healthcare Expenditure in Italy and Effects of Fingolimod Increased Prescribing in Second Line Treatment of Relapsing-Remitting Multiple Sclerosis:

Objectives To estimate the long-term comparative effectiveness of first-line treatment in patients negative for anti-JC virus (JCV) antibodies with glatiramer acetate (GA), fingolimod, or natalizumab for relapsing-remitting multiple sclerosis (RRMS). Study design We developed a simulation model to estimate the average 20-year clinical risks and benefits of GA, fingolimod, and natalizumab for RRMS patients initially negative for anti-JCV antibodies. Methods Model inputs included published natural history progressions of the Expanded Disability Status Scale (EDSS), treatment effects from randomized controlled trials on slowing disease progression and reducing relapse rates, risk of progressive multifocal leukoencephalopathy (PML), and utility preference scores. Outputs were long-term risks (PML risk and other non-PML risks), benefits (average relapse rate and time to disability [EDSS >7]), and quality-adjusted life years (QALYs). Results Compared with GA, natalizumab resulted in 4.6 fewer relapses, 0.6 more years of disability free time, 0.0165 more cases of PML per treated patient, and an incremental 1.2 QALYs gained. Compared with fingolimod, natalizumab resulted in 1.7 fewer relapses, 0.1 more years of disability free time, 0.0165 more cases of PML per treated patient, and an incremental 0.4 QALYs gained. The probability that incremental QALYs favored natalizumab over GA was 0.963 and natalizumab over fingolimod was 0.720. Conclusions Average QALYs, a measure that aggregates across risks and benefits, favored natalizumab, suggesting more aggressive early intervention with natalizumab in the negative anti-JCV population. For certain decision makers, more evidence may be needed to further reduce the uncertainty in these comparative projections prior to making population-based adoption decisions.

Comparative effectiveness of early natalizumab treatment in JC virus-negative relapsing-remitting multiple sclerosis.

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Comparative effectiveness of early natalizumab treatment in JC virus-negative relapsing-remitting multiple sclerosis.