Comparative Effectiveness and Cost-Effectiveness of Natalizumab and Fingolimod in Patients with Inadequate Response to Disease-Modifying Therapies in Relapsing-Remitting Multiple Sclerosis in the United Kingdom.

BACKGROUND: Patients with highly active relapsing-remitting multiple sclerosis inadequately responding to first-line therapies (interferon-based therapies, glatiramer acetate, dimethyl fumarate, and teriflunomide, known collectively as "BRACETD") often switch to natalizumab or fingolimod. OBJECTIVE: The aim was to estimate the comparative effectiveness of switching to natalizumab or fingolimod or within BRACETD using real-world data and to evaluate the cost-effectiveness of switching to natalizumab versus fingolimod using a United Kingdom (UK) third-party payer perspective. METHODS: Real-world data were obtained from MSBase for patients relapsing on BRACETD in the year before switching to natalizumab or fingolimod or within BRACETD. Three-way-multinomial-propensity-score-matched cohorts were identified, and comparisons between treatment groups were conducted for annualised relapse rate (ARR) and 6-month-confirmed disability worsening (CDW6M) and improvement (CDI6M). Results were applied in a cost-effectiveness model over a lifetime horizon using a published Markov structure with health states based on the Expanded Disability Status Scale. Other model parameters were obtained from the UK MS Survey 2015, published literature, and publicly available UK sources. RESULTS: The MSBase analysis found a significant reduction in ARR (rate ratio [RR] = 0.64; 95% confidence interval [CI] 0.57-0.72; p < 0.001) and an increase in CDI6M (hazard ratio [HR] = 1.67; 95% CI 1.30-2.15; p < 0.001) for switching to natalizumab compared with BRACETD. For switching to fingolimod, the reduction in ARR (RR = 0.91; 95% CI 0.81-1.03; p = 0.133) and increase in CDI6M (HR = 1.30; 95% CI 0.99-1.72; p = 0.058) compared with BRACETD were not significant. Switching to natalizumab was associated with a significant reduction in ARR (RR = 0.70; 95% CI 0.62-0.79; p < 0.001) and an increase in CDI6M (HR = 1.28; 95% CI 1.01-1.62; p = 0.040) compared to switching to fingolimod. No evidence of difference in CDW6M was found between treatment groups. Natalizumab dominated (higher quality-adjusted life-years [QALYs] and lower costs) fingolimod in the base-case cost-effectiveness analysis (0.453 higher QALYs and £20,843 lower costs per patient). Results were consistent across sensitivity analyses. CONCLUSIONS: This novel real-world analysis suggests a clinical benefit for therapy escalation to natalizumab versus fingolimod based on comparative effectiveness results, translating to higher QALYs and lower costs for UK patients inadequately responding to BRACETD.

Systematic assessment and characterization of chronic pain in multiple sclerosis patients.

Pain is one of the most disabling clinical symptoms in patients with multiple sclerosis (MS). Several studies have already assessed the prevalence of pain in MS patients, reporting variable results, probably due to methodological differences. The aim of this single-centre cross-sectional study was to define the prevalence and characteristics of chronic pain in a population of MS patients using validated tools, and to analyse these data in relation to demographic and clinical features, including disease duration and disability (EDSS and its single functional system scores). Of 397 enrolled patients, 23 were excluded due to a Beck's Depression Inventory Score > 19. In the remaining 374 patients, the overall prevalence of chronic pain was 52.1%, most frequently affecting the lower limbs (36.9%). Neuropathic pain was the most frequent type of chronic pain (89 patients, overall prevalence of 23.7%) and was associated with a sensory functional system involvement. Pain intensity was significantly higher in patients with neuropathic pain as opposed to patients with non-neuropathic pain. Patients with chronic pain and, in particular, patients with neuropathic pain had significantly higher EDSS scores than those without pain. Only 24% of patients with chronic pain and 33% of patients with neuropathic pain were on a specific long-lasting treatment for pain. The present study supports the routine assessment of neuropathic pain in MS patients, especially in those with a sensory functional system involvement, in order to avoid underdiagnosing and undertreating a potentially disabling condition.