Multiple sclerosis (MS) is a chronic and debilitating inflammatory autoimmune disorder of the central nervous system that afflicts approximately 400,000 people in the United States and 2.1 million people worldwide [1
]. MS is one of the most common contributors to neurological disability in young and middle-aged adults [3
]. The peak age of onset is approximately 30 years, and the disease occurs in twice as many women as men [4
]. About 85% of MS patients have the relapsing-remitting form of the disease [1
]. Symptoms of MS include fatigue, impaired mobility, spasticity, pain, depression, cognitive impairment, sexual dysfunction, bowel and bladder dysfunction, vision and hearing problems, seizures, and difficulty swallowing [2
]. The multifaceted symptoms of MS all are associated with economic burden, as well as an adverse impact on patients' quality of life.
Treatment of MS has advanced significantly over the past several decades. Historically, MS was treated in a solely supportive manner through symptomatic pharmacological treatment in the event of disease exacerbations (MS attacks), generally via powerful doses of short-course steroids [5
]. However, starting in the 1990s the FDA approved the first disease-modifying therapies (DMTs) for the long-term treatment of the disease. These new biologics were intended to proactively manage and retard disease progression. DMTs have demonstrated favorable risk-benefit profiles for US and other jurisdictions' regulatory approval. Some DMTs have more significant benefits and risks than others. DMTs have provided a promising new means of managing this chronic and debilitating disease; however, they have also introduced greatly elevated, and rapidly increasing, costs to the treatment of MS [6
]. Cost-of-illness studies in the early 2000s estimated that medication including DMTs accounted for ~7% of overall costs as reported across similar studies in Germany [7
], UK [8
], Sweden [9
], and Canada [10
]. In 2004, Kobelt found that in the US DMTs had begun to account for 34% of total costs per MS patient each year, and over half of all direct medical costs [11
]. Similarly, an Italian 2004 study suggested that 77% of direct medical costs were attributed to DMTs [12
]. On average DMTs cost $16,050 per MS-treated patient per year in 2004 dollars. By 2010, the current annual treatment costs had risen by two- to threefold over this 2004 average for all DMTs except mitoxantrone. The eight FDA approved DMTs as of August 2012 are characterized in .
Characteristics of disease-modifying therapies for multiple sclerosis.
Three review studies from 2003-4 focused on cost-effectiveness of DMTs in the treatment of MS and included multiple current therapies [3
]. In 2004, Flachenecker published a review that comprehensively studied all DMTs available at that time [25
]. In 2006, Kobelt published a review and informational article on studies of MS therapies; however, the focus was mainly methodological and did not compile and compare costs and effectiveness results in concert to inform decision makers [26
]. In 2006, Reickmann published a brief review on the socioeconomic aspects of neuroimmunological diseases focusing on MS [27
]. Prior reviews came to very similar conclusions suggesting use of the societal perspective, appropriate long-term modeling to reflect the chronic nature of MS, and standard endpoints and modeling to determine the cost-effectiveness of DMTs. The authors also indicated a dearth of comprehensive and uniform prospective studies, which is important in further understanding the costs and outcomes associated with different DMTs.
Over the past ten years, there has been a lack of comprehensive and systematic reviews of multiple sclerosis cost-effectiveness studies. Previous reviews did not address DMTs approved in recent years (natalizumab or fingolimod) and none have been recent and comprehensive enough to detail the current state of the cost-effectiveness of DMTs in treating multiple sclerosis. The aim of this systematic review was to provide a current and comprehensive understanding of the cost-effectiveness of DMTs for the treatment of multiple sclerosis by quantitatively evaluating the quality of cost-effectiveness studies and exploring how the multiple sclerosis cost-effectiveness field has progressed from past recommendations.