Economic Consequences of Persistence and Adherence to Lifelong Therapy for Patients with Presymptomatic Spinal Muscular Atrophy (SMA)

OBJECTIVES: Since 2017, three medications for the treatment of SMA have emerged: onasemnogene abeparvovec (OA; one-time, intravenously administered gene therapy), nusinersen (four loading doses and then every 4 months thereafter, intrathecally administered), and risdiplam (daily administered orally). For nusinersen and risdiplam, lifelong persistence and adherence are essential for attaining optimal treatment effectiveness. The objective of this study was to examine the economic impact of treatment persistence and adherence for patients with presymptomatic SMA in the United Kingdom.

METHODS: Data from published studies on persistence (time that medication is continued) and adherence (medication taken as prescribed) for nusinersen and risdiplam were extracted and extrapolated. An existing Markov model was used to simulate health benefits and costs over a lifetime for treated presymptomatic patients with SMA. The consequences of treatment discontinuation and non‑adherence were incorporated into the model. Costs and health benefits were discounted at 3.5%

RESULTS: Published persistence (42%–80% after 12 months) and adherence (27%–100%) rates for nusinersen and risdiplam varied by study, treatment, and subgroup. Suboptimal persistence led to a QALY loss of 2.5% for nusinersen and 2.4% for risdiplam. In addition, poor persistence lowered health care costs by 56% for nusinersen and 29% for risdiplam; both drugs were still more costly than OA. Health benefits and costs for OA remained unchanged at 25 QALYs and £2,096,927. Lack of adherence resulted in lowering drug costs by 15% and 0.8% for nusinersen and risdiplam, respectively, potentially lowering health benefits.

CONCLUSIONS: Previous studies on cost-effectiveness in SMA did not include the impact of persistence and adherence. This study demonstrates that reduced persistence and poor adherence led to a loss in QALYs and a reduction in drug costs. Nevertheless, one-time therapy with OA for patients with presymptomatic SMA remains the least costly treatment option and delivers optimal health benefits.