Feng et al. (10) performed a 21-year long-term follow-up study by using a Markov model to stimulate the experience of MS patients over a lifetime from a societal perspective, and outlines that in some studies in the US, DMTs are calculated to be cost-effective. Patients were randomised to receive interferon beta-1b treatment or placebo for up to 5 years and then were given a variety of treatments afterwards. Unlike other studies, this cost-effectiveness analysis specifically included information on the survival benefit of interferon beta-1b treatment, and didn’t assume the risk of death to be similar to that of the general population, greatly improving the reliability of their results. Annual discount rates of 3% were given to adjust future costs to present costs, and health outcomes were measured as incremental cost per QALY, thus permitting the results to be easily comparable to other studies. The incremental cost-effectiveness ratio (ICER) of IFBN-1b was $46,357/QALY, which can be argued as a cost-effective therapy. However, the research was funded by Bayer Healthcare who develop and market IFNB-1b (Betaseron), which introduces bias due to conflict of interest.
Caloyeras et al. (14) also used a Markov model to estimate health outcomes and costs for a hypothetical cohort of Swedish patients, with outcomes measured from a societal perspective and a life-time 50-year horizon, and highlighted the importance and cost-effectiveness benefits of early DMT therapy. The Expanded Disability Status Scale (EDSS) was used to define health states for patients with relapsing forms of MS, whereas health outcomes were too measured in QALYs, ICER and indirect and direct costs with annual discounts of 3%. The analysis found that early treatment with IFNB-1b produced lower costs and greater effectiveness than treatment delayed. Core data source for the model inputs were based on data from a double-blind placebo-controlled BENEFIT RTC, however when data were not available from the trial, parameters were populated using extrapolations. Although the validity of the model was assessed using a sensitivity analysis, it is still worth bearing this in mind, as it could reduce transferability of results to real-world scenarios.
Early treatment showed an increase in QALYs gained (12.9 QALYs) over delayed treatment (12.4 QALYs). Patients accumulated higher direct medical costs with early treatment, however incurred significantly lower direct non-medical costs over a 50-year time horizon. At the beginning of treatment, the clinical benefits of early treatment were not fully experienced. The study highlights when time is increased beyond 10 years, the cost per patient per QALY gained was dramatically reduced, and thus concluded that the ICER increased with shorter time horizons. The population was based on Swedish MS patients, meaning costs and ICERs were not transferable to an American population, however the conclusions regarding the importance of longer time horizons stands.
Palace et al. (11) aimed to evaluate the long-term effectiveness and cost-effectiveness of these DMTs by comparing a cohort of patients with relapsing-remitting multiple sclerosis in the UK with a control cohort from British Columbia, Canada. The study presented results for disability progression and cost-effectiveness of treatments at 6 years. MS patients were aged 18 or older, had an EDSS score of 5.5 or lower and had had two clinically significant relapses in the past two years. Study findings showed after a 6-year follow-up and 20-year horizon trajectory, IFNB-1b and glatiramer acetate reduced disability progression by 24-40% and were cost-effective in terms of the UK’s NICE guidelines of £36,000 per QALY gained, although the study failed to disclose the number of QALYs gained, or a specific ICER value. Although the studies deemed both first-line DMTs to be cost-effective against a control, a comparison against the two therapies would have provided useful information regarding which specific DMT was the most cost-effective. Again however, the transferability of results from different countries proves difficult, which is highlighted by the authors, who disclosed that cost-effectiveness would not necessarily be achieved for countries with higher drug costs, without a Risk Sharing Scheme (RSS). This scheme between UK health departments, MS Trust and drug manufactures, reduced drug costs when necessary to meet a cost effective ICER of £36,000 per QALY gained, projected over 20 years, and could be hugely beneficial for MS patients in the USA if adopted.
Lawrence et al. (12) conducted a cost-effective analysis for first-line RRMS treatments, after highlighting the high economic burden associated with the chronic disease. The study developed an evidence-based economic model to assess cost-effectiveness of the four first-line DMTs. Parameter inputs for the model included data from randomised placebo-controlled RCTs, however the RCTs were all conducted in the 1990’s, which may not reflect current prices. The evaluation was conducted from the perspective of the payers, so indirect costs were not included. However, it was noted that a cost of one relapse can be as high as $16,589 and that cost of long-term treatments were encouraging healthcare payers to find more cost-effective measures. The study found the most cost-effective DMT was IFNB-1a administered subcutaneously, at a total MS-related cost of $59,449 over a two-year period. The health outcome ICER measurement used was cost per relapse avoided, which for IFNB-1a SC totalled $80,589, compared to $88,310 for Glatiramer Acetate and $87,061 for IFNB-1b SC. A two-year time horizon was used and based on the 2-year RCTs, without extrapolating to a lifetime time horizon, which could result in significantly higher treatment costs and higher ICERs as shown by Caloyeras et al. (14). Additionally, MS patients entering the model could not have an EDSS <3.0, meaning it was likely the significant cost-effectiveness of early-treatment effects seen with Palace et al. (11) were not present. Conflict of interest bias may be present, as the study was sponsored by EMD Serono, Inc., the manufactured of interferon ?-1a subcutaneous injection.