Cost effectiveness of nusinersen for patients with infantile-onset spinal muscular atrophy in US

Background Patients with infantile-onset spinal muscular atrophy (SMA), a rare, genetic neuromuscular disease, do not achieve key motor function milestones (e.g., sitting) and have short life expectancy in the absence of treatment. Nusinersen is a disease-modifying therapy for patients with SMA. Objective The aim of this study was to estimate the cost-effectiveness of nusinersen compared to best supportive care (BSC) in patients diagnosed with infantile-onset SMA in the US. Methods A de novo economic model was developed with the following health states: “permanent ventilation”, “not sitting”, “sitting”, “walking”, and “death”. Short-term data were sourced from the pivotal clinical trials and studies of nusinersen (ENDEAR and SHINE). Motor function milestones achieved at the end of follow-up in the clinical trials were assumed to be sustained until death. Mortality risks were based on survival modelling of relevant published Kaplan–Meier data. Costs, life years (LYs), and quality-adjusted life years (QALYs) were discounted at 3% per annum, and the analyses were performed from a US health care sector perspective. Scenario analyses and sensitivity analyses were conducted to assess the robustness of the results to key parameters. Results In our base-case analysis, nusinersen treatment achieves greater QALYs and more LYs (3.24 and 7.64, respectively) compared with BSC (0.46 QALYs and 2.40 LYs, respectively), resulting in an incremental cost per QALY gained of approximately $1,112,000 and an incremental cost per LY gained of$590,000 for nusinersen compared to BSC. The incremental cost effectiveness ratios did not fall below $990,000 per QALY gained in scenario and sensitivity analyses. Results were most sensitive to the length of survival, background health care costs, and utility in the “not sitting” and “sitting” health states. Conclusions The estimated incremental cost-effectiveness of nusinersen from a US health care sector perspective exceeded traditional cost-effectiveness thresholds. Cost-effectiveness was dependent on assumptions made regarding survival, costs, utilities, and whether the motor function milestones were sustained over lifetime. Given the relatively short-term effectiveness data available for the treatment, a registry to collect long-term data of infantile-onset SMA patients is recommended

Effect of treatment modality and cerebral vasospasm agent on patient outcomes after aneurysmal subarachnoid hemorrhage in the elderly aged 75 years and older.

OBJECTIVE:We sought to examine whether the effect of treatment modality and drugs for cerebral vasospasm on clinical outcomes differs between elderly and non-elderly subarachnoid hemorrhage (SAH) patients in Japan. METHODS:We analyzed the J-ASPECT Study Diagnosis Procedure Combination database (n = 17,343) that underwent clipping or coiling between 2010 and 2014 in 579 hospitals. We stratified patients into two groups according to their age (elderly [≥75 years old], n = 3,885; non-elderly, n = 13,458). We analyzed the effect of treatment modality and anti-vasospasm agents (fasudil hydrochloride, ozagrel sodium, cilostazol, statin, eicosapentaenoic acid [EPA], and edaravone) on in-hospital poor outcomes (mRS 3-6 at discharge) and mortality using multivariable analysis. RESULTS:The elderly patients were more likely to be female, have impaired levels of consciousness and comorbidity, and less likely to be treated with clipping and anti-vasospasm agents, except for ozagrel sodium and statin. In-hospital mortality and poor outcomes were higher in the elderly (15.8% vs. 8.5%, 71.7% vs. 36.5%). Coiling was associated with higher mortality (odds ratio 1.43, 95% confidence interval 1.2-1.7) despite a lower proportion of poor outcomes (0.84, 0.75-0.94) in the non-elderly, in contrast to no effect on clinical outcomes in the elderly. A comparable effect of anti-vasospasm agents on mortality was observed between non-elderly and elderly for fasudil hydrochloride (non-elderly: 0.20, 0.17-0.24), statin (0.63, 0.50-0.79), ozagrel sodium (0.72, 0.60-0.86), and cilostazol (0.63, 0.51-0.77). Poor outcomes were inversely associated with fasudil hydrochloride (0.59, 0.51-0.68), statin (0.84, 0.75-0.94), and EPA (0.83, 0.72-0.94) use in the non-elderly. No effect of these agents on poor outcomes was observed in the elderly. CONCLUSIONS:In contrast to the non-elderly, no effect of treatment modality on clinical outcomes were observed in the elderly. A comparable effect of anti-vasospasm agents was observed on mortality, but not on functional outcomes, between the non-elderly and elderly