Examining Real-World Adherence to Nusinersen for the Treatment of Spinal Muscular Atrophy Using Two Large US Data Sources

Abstract

Introduction Spinal muscular atrophy (SMA) is a rare neuromuscular disease characterized by progressive muscular atrophy and weakness. Nusinersen was the first treatment approved for SMA. Per the US label, the nusinersen administration schedule consists of three loading doses at 14-day intervals, a fourth loading dose 30 days later, and maintenance doses every 4 months thereafter. Using two large US databases, we evaluated real-world adherence to nusinersen with its unique dosing schedule among generalizable populations of patients with SMA. Methods Patients with SMA treated with nusinersen, likely to have complete information on date of treatment initiation, were identified in the Optum ® de-identified electronic health records (EHR) database (7/2017–9/2019), and in the Merative™ MarketScan ® Research Databases from commercial (1/2017–6/2020) and Medicaid claims (1/2017–12/2019). Baseline demographics, number of nusinersen administrations on time, and distribution of inter-dose intervals were summarized. Results Totals of 67 and 291 patients were identified in the EHR and claims databases, respectively. Most nusinersen doses were received on time (93.9% EHR, 80.5% claims). Adherence was higher during the maintenance phase (90.6%) than the loading phase (71.1%) in the claims analysis, in contrast with the EHR analysis (95.5% and 92.6%, respectively), suggesting that not all loading doses of nusinersen may be accurately captured in claims. Inter-dose intervals captured in both databases aligned with the expected dosing schedule. Conclusion Most nusinersen doses were received on time, consistent with the recommended schedule. Our findings also highlight the importance of careful methodological approaches when using real-world administrative databases for evaluation of nusinersen treatment patterns. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-022-02414-9.

Adherence and Persistence Among Risdiplam-Treated Individuals with Spinal Muscular Atrophy: A Retrospective Claims Analysis

“…The differences observed between nusinersen and risdiplam in adherence and persistence may also be related to different study methodologies, including how adherence and persistence were defined, datasets used, number of individuals included, and length of follow-up. As a result of the nature of the dosing administration of nusinersen, adherence can be calculated at the patient level [ 21 ], dose level [ 22 ], or both [ 20 ]. Patient-level adherence considers the adherence of each individual within the study population to estimate a population’s overall adherence.…”

“…Dose-level adherence could be highly influenced by a small number of patients contributing more doses within the analysis [ 37 ]. For example, analyses of nusinersen adherence at the dose level (e.g., Youn et al) [ 22 ] have reported higher levels of adherence to nusinersen than studies analyzing adherence at the patient level (e.g., Fox et al) [ 21 ]. Differences in adherence at the dose level (e.g., 72–76%) versus at the patient level (e.g., 27–44%) are apparent even within the same study [ 20 ].…”

“…In addition, Elman et al [ 38 ] reported adherence and persistence data from nine SMA specialized centers, whereas Gauthier-Loiselle et al [ 20 ] and Fox et al [ 21 ] made use of nationally representative claims databases. Specialized treatment centers such as those reported by Elman et al may report higher rates of medication adherence and persistence, as they have a higher concentration of resources and individuals with expertise in a specific disease area [ 22 , 33 ].…”

“…Long-term adherence may also reduce associated comorbidities and hospitalizations, which may subsequently reduce healthcare costs and healthcare resource utilization [20][21][22][23]. Some individuals with SMA and their caregivers may prefer an oral therapy [24]; however, no data exist regarding real-world patient adherence to and persistence with risdiplam, the only oral at-home treatment for SMA.…”