Untackling the economics of multiple sclerosis: A systematic review of economic evaluations of disease-modifying therapies indicated for multiple sclerosis

Objectives: Multiple sclerosis (MS) comprises a chronic, neurodegenerative, and inflammatory illness of the central nervous system that affects 2.8 million people worldwide. MS is only treatable, and to this direction, the disease armamentarium has been significantly enriched with new agents, albeit with burgeoning costs and engulfed by uncertainty. The scope of this review is to assess the efficiency of MS agents.

Methods: We performed a systematic literature review, spanning from 2000 to 2023 on adult patients with any form of MS, receiving any MS indicated modality and whose outcome was ICUR and ICER. The methodological quality of the studies was assessed with the Quality of Health Economics Studies tool.

Results: We identified 57 studies that met the inclusion criteria. Studies were hailing from 20 countries and a multitude of methodological approaches were documented across several types of MS. A substantial level of divergence regarding results was noted. Country setting, study perspective (societal vs payer) the selection of the benchmark treatment, data extrapolation beyond the reported timeframe of the trial and time horizon of the model exerted a substantial impact on the results. Dimethyl fumarate was consistently interrelated with a positive cost-effectiveness ratio. The same applies for fampridine, while Cladribine was proved to be a dominating agent. Ocrelizumab also evinced efficiency. The same applies for the early data of Siponimod and ofatumumab, however the breadth of their studies lags compares to other agents, and these results have to be further corroborated. On the contrary Interferons demonstrated a non-efficient profile and their use as a comparative benchmark arm brought about several complications regarding the incremental financial aspect of economic evaluations, since they are commonly used as such. The results of fingolimod and natalizumab studies are embroiled in uncertainty. Moreover, the efficiency factor was positively correlated by earlier access of patients to these products, rather than delayed one. Result discrepancies among the same country were also imputed to the adopted utility and disutility values and the methodological approach for data extrapolation. Results were sensitive to an array of factors. Among them, the effectiveness of the products, coupled with the cost of the agents emerged as the most important drivers. Uncertainty was further compounded by several other parameters such as discounting, efficacy waning, horizon of the study, disability base rate and utility of the patients. We also outlined that the efficiency of product is pertinent to the disease type. Results such as dominance must be interpreted with caution since in certain cases a dominating agent was proved to be as such by capitalizing on marginal incremental health gains, compared to the standard comparative treatment.

Conclusions: An increasing body of evidence consisting of economic evaluations for MS was retrieved. These studies exhibited high quality, however, the consistency regarding results was impaired.