Newborn Screening Associated With Earlier Diagnosis, Greater Outcomes in SMA

Richard Finkel, MD

Real-world results from the RESTORE (NCT04174157) registry analysis presented at the Muscular Dystrophy Association (MDA) 2021 Clinical and Scientific Conference, March 15-18, revealed that newborn screening (NBS) for spinal muscular atrophy (SMA) is associated with significantly earlier diagnosis and intervention.

Senior author Richard Finkel, MD, director, Experimental Neurotherapeutics, St. Jude Children’s Research Hospital, who presented the data at the meeting, and colleagues identified a total of 28 patients by NBS compared with 56 patients who were clinically diagnosed.

For clinically diagnosed patients compared with NBS patients, mean age at diagnosis was 3.5 versus 0.8 months, respectively. Furthermore, average age at first treatment was 4.4 months for those clinically diagnosed compared to 1.7 months for NBS. Time to diagnosis to treatment was 0.9 months for both groups.

Finkel and colleagues also found a greater number of those who were clinically diagnosed received more than 1 SMA therapy. All told, 71.4% (n = 40) and 28.6% (n = 8) of clinically diagnosed and NBS patients received more than 1 SMA therapy, respectively (P <.0001).

"Our study may stimulate discussion and suggest new lines of inquiry regarding barriers to NBS implementation and reasons for delay between diagnosis and treatment,” Finkel et al concluded.

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Motor function changes using Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) scores were also documented. Among available data, increases greater than 4 points were observed for 68.2% (15 of 22) of clinically diagnosed patients and 88.9% (8 of 9) of patients identified by NBS, a difference of 20.7% in favor of the NBS group (P = .1514).

Those in the NBS group also recorded a greater mean change in overall CHOP-INTEND scores compared to those clinically diagnosed (1.5 points/month), a difference of 1.2 points (P = .1065).

The RESTORE registry also included patients in the onasemnogene abeparvovec (Zolgensma; Novartis) managed access program and new enrollees from partnering clinical sites. Of the patients receiving monotherapy (clinically diagnosed: n = 16; NBS: n = 20), most patients in both groups received onasemnogene abeparvovec (vs nusinersen [Spinraza; Biogen]; 87.5% vs 90.0%, respectively).

The investigators noted multiple limitations to the study, including the small number of patients, variable completeness of data across study sites at time of analysis, and the short, variable duration of follow-up.

They also noted that effectiveness data available for this analysis was limited; however, this was expected due to the fact that patients in RESTORE are evaluated in a routine practice setting where motor function testing and/or milestones are not assessed as regularly compared to an interventional trial.

For years, clinicians within the SMA community have echoed the benefits NBS can have for patients with SMA. Mary Schroth, MD, chief medical officer of Cure SMA, has mentioned that 1 of the organization’s biggest goals is to get NBS initiated in every state in the US. Even if this goal is achieved, around 5% of infants with SMA will still remain unidentified due to the limitations in the technology. Listen to our conversation with her below, as she advocates for the need of NBS.

For more coverage of MDA 2021, click here.

REFERENCE

Servais L, De Vivo D, Kirschner J, et al. Newborn screening for spinal muscular atrophy in the United States: early findings from the RESTORE registry. Presented at MDA Clinical and Scientific Conference 2021; March 15-18.