A microsimulation model published in Value in Health estimated the effectiveness and cost-effectiveness of 360 treatment sequences in terms of health outcomes and societal costs, beginning with first-line therapies in relapsed-remitting multiple sclerosis (RRMS).

The decision-analytic modeling conducted in the Netherlands integrated different data sources and included information on “disease progression, disease-modifying treatment efficacy, clinical decision rules, age-dependent relapse rates, quality of life, healthcare, and societal costs” to estimate total lifetime benefit.

The results demonstrated that the most effective treatment escalation sequences are not the most cost-effective treatment sequences. Optimal lifetime health outcomes (20.24 ±1.43 quality-adjusted life-years [QALYs], 6.11 ± 0.30 relapses) occurred with the treatment sequence of peginterferon-dimethyl fumarate-ocrelizumab-natalizumab-alemtuzumab. However, the most cost-effective sequence was peginterferon-glatiramer acetate-ocrelizumab-cladribine-alemtuzumab, which resulted in a cost-savings of €98,127 ± €19,134, compared to the most effective treatment sequence, but worse health outcomes (19.59 ± 1.43 QALYs, 6.64 ± 0.43 relapses).

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The model demonstrated good short-term prediction of the number of treatment switches within the first 5 years for patients with Dutch MS, thus validating its short-term predictive value. However, when considering the results of this analysis, it is clear that the decision rules are country-specific and to some extent even physician-specific.

This report uses parameters based on data from average patients with MS. Therefore, applicability is limited as it does not take into account the unique characteristics and preferences of individual patients such as comorbidities, treatment adherence, pregnancy wishes, and preferences for administration mode. This model also does not incorporate differential effects between subgroups, such as patients at high and low risk of relapses. Therefore, treatment decisions should be individually tailored.

According to this model, implementing the most effective treatment sequences could reduce resources available for overall population health. When considering cost-effectiveness, the authors state that their model “may help to raise awareness among policymakers and neurologists that choices regarding therapy have a consequence on how much health can be gained in a population given healthcare budget constraints.”


Versteegh MM, Huygens SA, Wokke BWH, Smolders J. Effectiveness and cost-effectiveness of 360 disease-modifying treatment escalation sequences in multiple sclerosis. Value in Health. Published online December 15, 2021. doi:10.1016/j.jval.2021.11.1363