Long-Term Cost-Effectiveness Model of Interferon Beta-1b in the Early Treatment of Multiple Sclerosis in the United States

Abstract

Background

Multiple sclerosis (MS) is a potentially debilitating autoimmune disease that affects the brain and spinal cord. Disease-modifying therapies have been shown to slow disease progression but were not believed to prolong the survival of patients with MS. The recent 21-Year Long-Term Follow-Up (21Y-LTF) study found a significant survival advantage for patients receiving early treatment with interferon beta (IFNβ)-1b compared with placebo (no early treatment).

Objectives

The aim of this study was to conduct cost-effectiveness analyses estimating the long-term benefit of early treatment with IFNβ-1b among MS patients from a US societal perspective.

Methods

A Markov model was developed to simulate the experience of patients with MS from the 21Y-LTF study over a lifetime. Patients were randomized to receive either IFNβ-1b or placebo for up to 5 years and then receive a variety of MS treatments (including no treatment) thereafter. Survival data reported from the 21Y-LTF study were incorporated into the model. The model assumes that patients' MS was managed in similar ways for both groups during the uncontrolled phase of the 21Y-LTF study (ie, survival difference between the 2 groups is the result of early use of IFNβ-1b). Health outcomes were life-years and quality-adjusted life-years (QALYs). Costs included treatments, direct disease management, informal care, and lost productivities and were reported in 2011 US dollars.

Results

In the modeled placebo group, the median age at death was predicted to be 63.7 years, and the median survival time from disease onset was 36.7 years. Early treatment with IFNβ-1b reduced the lost health benefits by 2.8 life-years and 1.9 QALYs, respectively, after discounting. Total discounted cost for IFNβ-1b–treated patients was $86,223 higher than that of patients receiving placebo. The incremental cost-effectiveness ratio was $46,357 per QALY gained and $30,967 per life-year gained. Sensitivity analyses indicate the robustness of the model's results.

Conclusions

Treatment with IFNβ-1b during the earlier disease phase of patients with MS significantly increased patient life-years and QALYs. IFNβ-1b is likely to be a cost-effective intervention for MS.

Introduction

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease that impairs the brain and spinal cord. There is no cure for MS, and the safest and most reliable medications available are disease-modifying therapies (DMTs), which were introduced in the 1990s to slow down or alter the natural course of MS to enhance patient quality of life. Although evidence1, 2, 3, 4, 5, 6, 7 suggests that these drugs delay disease progression and reduce the incidence of relapses in patients with MS, the effects of DMTs on long-term survival outcomes are much less understood. Several recent, large-scale, population-based mortality studies and registries, however, demonstrate a distinct survival disadvantage (7−14 years) in MS patients compared with the general population,8, 9, 10, 11, 12, 13 with differences emerging as early as 2 to 10 years after the MS diagnosis.¹²

As a reaction to the lack of definitive long-term data regarding the impact of DMT on survival/mortality in MS patients, the 21-Year Long-Term Follow-Up (21Y-LTF)¹⁴ study to the interferon beta (IFNβ)-1b pivotal trial1, 2 was undertaken. The 21Y-LTF study assessed the effects of IFNβ-1b on mortality by examining 372 patients who participated in the IFNβ-1b pivotal trial 21 years after the trial was initiated. At the 21-year follow-up, the study found a statistically significant survival advantage for patients randomized to receive earlier treatment with IFNβ-1b 250 μg compared with placebo (no early treatment), with a hazard ratio of 0.532 (95% CI, 0.314–0.902). With near-complete patient ascertainment (98.4%), a randomized controlled trial design approach, and the longest period of follow-up for a treatment-exposed MS population, this study provides valuable insights into the effect of IFNβ-1b on all-cause mortality outcomes in MS patients, as well as a strong indication about this agent's potential role in prolonging the survival of patients with MS.

To simulate the long-term benefit of IFNβ-1b in the early treatment of patients with relapse-remitting MS (RRMS) in the United States, we present a cost-effectiveness model that was developed based on the findings of the 21Y-LTF study.¹⁴ The analysis adopts the societal perspective, with considerations of higher mortality risks for MS patients and an observed survival benefit associated with early IFNβ-1b treatment. This is the fundamental difference between the design of our cost-effectiveness study and previous economic studies in MS, as many published models only consider the effect of treatments on disease progression but not on the survival benefit.15, 16, 17, 18 In addition, our cost-effectiveness analysis evaluated the MS cohort over a lifetime (70 years) to accurately portray the chronic disease nature of MS and fully capture the survival benefits associated with IFNβ-1b treatment. Some cost-effectiveness publications16, 17 considering shorter-term (eg, 10 years) outcomes have suggested a high cost for modest health gains for DMTs in MS care. Our study attempts to investigate the cost-effectiveness outcomes over a longer time horizon. We obtained cost and utilization estimates by using the resource use pattern and quality of life data of a recently surveyed nationally representative MS population in the United States.¹⁹ With this approach, our cost-effectiveness model results are expected to override the concerns raised in existing models for the US patient population, where the analyses are often based on information from outdated cost and utility sources or the use of small convenience samples for utility predictions.15, 17, 18