MS Speaks

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

David Bargiela1, Matt Bianchi2, Brandon Westover2, Brian Healy1, Philip De Jager3, Zongqi Xia4

1
Brigham and Women's Hospital, 2 Massachusetts General Hospital, 3 Brigham & Women's Hospital, 4 University of Pittsburgh

Objective:

To integrate long-term measures of disease-modifying drugs (DMDs) efficacy and risk to guide selection of first-line treatment of multiple sclerosis (MS).

Background:

With the growing choices of DMDs, there is an increasing need for stratified treatment guidance in MS due to variable responses and adverse events. However, head-to-head comparison of DMDs that includes a broad range of risk profiles and long-term outcomes is challenging to perform.

Design/Methods:

We created a Markov decision model to evaluate disability worsening and progressive multifocal leukoencephalopathy (PML) risk in patients receiving three representative DMDs across 30 years: natalizumab (NTZ), fingolimod (FGL) or glatiramer acetate (GA).

Leveraging publicly available data, we integrated treatment
utility, disability worsening and risk of PML into quality-adjusted life-years (QALYs). We performed extensive 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 (from all causes). NTZ treatment is associated with delayed
worsening to an Expanded Disability Status Scale score ≥6.0 versus FGL or GA (22.7 years, 17.0 years and 12.4 years, respectively).

When compared to untreated patients, NTZ-treated patients have 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 when compared to FGL or GA. Integrated modelling of long-term treatment risks and benefits informs
stratified clinical decision-making and can support patient counselling on selection of first-line treatment options.

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Study Supported by:

None relevant to this study.