The changing natural history of spinal muscular atrophy type 1

Abstract

Background: Noninvasive ventilation has become increasingly available to spinal muscular atrophy (SMA) patients since the early 1990s. This is expected to have improved survival for SMA type 1 patients. Objective: To assess whether there has been a change in survival in patients with SMA type 1 between 1980 and 2006. Methods: We used deidentified, family-reported data from participants in the International Spinal Muscular Atrophy Patient Registry and obtained additional clinical information through a mail-in questionnaire. One hundred forty-three patients with SMA type 1 were included in the analysis. Survival of patients born in 1995–2006 (n = 78) was compared with that of patients born in 1980–1994 (n = 65), using the Kaplan–Meier method and Cox proportional hazards models with age at death as the outcome. Results: Patients born in 1995 though 2006 had significantly increased survival compared with those born in 1980–1994 (log-rank test, p < 0.001). In a Cox model, patients born in 1995–2006 had a 70% reduction in the risk of death compared with those born in 1980–1994 (hazard ratio [HR] 0.3, 95% CI 0.2–0.5, p < 0.001) over a mean follow-up of 49.9 months (SD 61.1, median 22.0). However, when controlling for demographic and clinical care variables, year of birth was no longer significantly associated with age at death (HR 1.0, 95% CI 0.6–1.8, p = 0.9), whereas ventilation for more than 16 h/d, use of a mechanical insufflation–exsufflation device, and gastrostomy tube feeding showed a significant effect in reducing the risk of death. Conclusion: Survival in spinal muscular atrophy type 1 patients has increased in recent years, in relation to the growing trend toward more proactive clinical care. GLOSSARY: BiPAP = bilevel positive airway pressure; HR = hazard ratio; MI-E = mechanical insufflation–exsufflation; SMA = spinal muscular atrophy; YOB = year of birth.