An Indirect Comparison of Therapies for Multiple Sclerosis

Cincinnati—The mean annual costs of treating multiple sclerosis (MS) rise with increasing disability, imposing a considerable economic burden on society, according to researchers. It is important for payers making formulary decisions to be able to identify interventions that are not only efficacious, but also cost-effective. At best, formulary decision-making is based on comparisons of results of direct, head-to-head trials.

A major challenge to cost-effectiveness models in MS treatment is heterogeneity of randomized clinical trials (RCTs). To accommodate the heterogeneity found across clinical trials, indirect comparative methods are used. For example, mixed treatment comparison (MTC) compares multiple interventions from clinical trials with different controls, using indirect evidence estimates.

Researchers recently conducted a study to adapt an existing cost-effectiveness model comparing oral fingolimod with other first-line disease modifying treatments (DMTs) using the results of a published MTC. They reported results during a poster session at the AMCP meeting. The poster was titled Cost-Effectiveness of Multiple Sclerosis Therapies: An Indirect Comparison.

The original cost-effectiveness model calculated the cost per relapse avoided for different DMTs used as a first-line treatment of relapsing-remitting MS, including oral fingolimod, subcutaneous (SC) and intramuscular (IM) interferon (IFN)-beta-1a and IFN-beta-1b, and glatiramer acetate. Relapse rate outcomes were derived from pivotal clinical trials as included in the respective FDA-approved Package Inserts; cost per relapse avoided was calculated as the 2-year total cost of therapy divided by the number of relapses avoided over the same period.

The original model was adapted to include the MTC results as efficacy inputs in place of the relative relapse reduction (RRR) from the clinical trials. Results of the adapted model were compared to the original model.

Compared with placebo, the adjusted RRRs in the MTC were 57% for fingolimod, 35% for SC IFN-beta-1b (Extavia^®), 35% for IFN-beat-1b (Betaseron^®), 38% for glatiramer acetate, 34% for SC IFN-beta-1a, and 17% for IM IFN-beta-1a.

The original model showed that, despite a higher 2-year cost of therapy for oral fingolimod, the cost per relapse avoided over 2 years was lowest for fingolimod and highest for IM IFN beta-1a ($74,834 vs $197,073). Using RRR parameter estimates for the MTC, the cost per relapse avoided over 2 years remained lowest for fingolimod and highest for IM IFN-beta-1a ($83,853 vs $237,872).

Sensitivity analyses showed that the results were robust and the rank-order of the results remained unaffected by the use of the original unadjusted RRR estimates or the MTC estimates.

The researchers cited a few limitations: (1) MTCs are less reliable than head-to-head trials because the end point definitions differ among the trials and point estimates may not enable full adjustment for differences in study populations across trials and (2) the impact of disability progression on costs was not included in either the original or the MTC model because the costs of care were only included over a short, 2-year period and costs of disability progression are usually incurred over a 10+ year period.

In conclusion, the researchers said, “Treatment with oral fingolimod is cost-effective, having the lowest cost per relapse avoided among the other first-line DMTs investigated. Based on the MTC, oral fingolimod significantly reduced relapse frequency over other DMTs used a first-line therapy.”

This study was supported by Novartis Pharmaceuticals.