The cost-effectiveness of disease-modifying therapies for the treatment of relapsing-remitting multiple sclerosis

Background: The safety and efficacy of disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS) has been established; however, it is not clear which provides optimal value, given benefit-risk profiles and costs.

Aims: To compare the cost-effectiveness of current DMTs for patients with RRMS in the US.

Materials and methods: A Markov model predicting RRMS course following initiation of a DMT was created comparing outcomes (e.g. relapses, disease progression) and costs of natalizumab (NTZ), dimethyl fumarate (DMF), and peginterferon beta-1a (PEG) with fingolimod (FIN), glatiramer acetate (GA, 20?mg daily), and subcutaneous interferon beta-1a (IFN, 44?mcg), respectively, over 10 years. RRMS and secondary-progressive MS (SPMS) EDSS state transitions were predicted in 3-month cycles in which patients were at risk of death, relapse, or discontinuation. Upon DMT discontinuation, natural history progression and relapse rates were applied. Incremental cost-effectiveness ratios (ICERs) were estimated for the cost per relapse avoided, relapse-free years gained, progression avoided, and progression-free years gained. The impact of model parameters on outcomes was evaluated via one-way sensitivity analyses.

Results: Costs ranged from $561,177 (NTZ) to $616,251 (GA). NTZ, DMF, and PEG were dominant (less costly and more effective) compared to FIN, GA, and IFN, respectively, for all ICERs. Variability in drug costs and parameters that affected drug cost accrual (e.g. discontinuation rates and the decision to drop out after SPMS conversion) had a considerable impact on ICERs.

Limitations: Several simplifying assumptions were made that may represent potential limitations of this analysis (e.g. a constant treatment effect over time was assumed).

Conclusions: The results from this analysis suggest that the NTZ, DMF, and PEG are cost-effective DMT choices compared to FIN, GA, and IFN, respectively. The actual impact on a particular plan will vary based on drug pricing and other factors affecting drug cost accrual.     

Estimating the rates of disability progression in people with active relapsing-remitting multiple sclerosis

SUMMARY

Estimated progression rates for people with active relapsing-remitting multiple sclerosis (RRMS) are essential for resource management but are poorly quantified according to disability severity. In this study data from the placebo arm of the AFFIRM study were used to estimate rates for a population of active RRMS patients and for a rapidly evolving severe (RES) subgroup of RRMS patients. A multistate Markov model was fitted to the data to derive a matrix of annual transition probabilities between disability states. The average progression over 2 years was estimated to be 0.27 Expanded Stability Status (EDSS) points (95% confidence interval (CI) 0.11-0.43) for active RRMS patients and 0.46 EDSS points (95% CI 0.16-0.79) for the RES subgroup. When similar baseline characteristics were used, progression in the RES subgroup was approximately 0.06-0.08 EDSS points faster per year than active RRMS patients. These results may be used for long-term forecasts of progression of these patient groups when used in conjunction with transition rates from RRMS to secondary progressive multiple sclerosis, and between secondary progressive multiple sclerosis EDSS states.