Reduction in Perioperative Risk in Patients with Spinal Muscular Atrophy Following the Release of Disease-Modifying Therapies: An Analysis of the National Surgical Quality Improvement Program Database.

Background/

Objectives

Spinal muscular atrophy (SMA) is a progressive neurodegenerative disease resulting in proximal muscle weakness and paralysis. SMA treatment has radically changed in the past 10 years thanks to the development of novel therapies such as nusinersen and onasemnogene abeparvovec. Since the advent of new treatments, the incidence and perioperative risk factors of patients with SMA undergoing longer, higher-risk surgeries are unknown. We hypothesized that patients with SMA would be at an overall elevated risk for postoperative pulmonary complications (PPC) and prolonged length of stay compared to the general population, but that this would be reduced in patients undergoing surgery in the years after the release of new therapies.

Methods

Patients who underwent surgery at a continuously enrolled American College of Surgeons National Surgery Quality Improvement Program-Pediatric hospital from 1 January 2012, to 31 December 2021, were included in this study. Cases with missing covariate or primary outcome data were excluded from the analysis. Patients with ages greater than 17 years, preoperative tracheostomy, preoperative mechanical ventilation, missing covariate or primary outcome data were excluded. Patients with SMA were identified by their ICD-9 and 10 codes. A cutoff year of 2018 was chosen for analysis of the primary outcomes as this was a full year after nusinersen received FDA approval.

Results

On univariable analysis, the risk for PPC in patients with SMA was reduced in patients undergoing surgery in 2018 or later compared to pre-2018 (pre-2018 OR 4.44, 95% CI 1.56-9.6, p = 0.008; post-2018 OR 3.48, 95% CI 0.84-9.12, p = 0.08). On multivariable analysis, the association between SMA and PPC substantially decreased in 2018 and after but was no longer statistically significant (pre-2018 OR 1.96, 95% CI 0.80-4.80, p = 0.14; post-2018 OR 1.03, 95% CI 0.33-3.26, p = 0.96). SMA was positively associated with LOS in the pre-2018 cohort, with a coefficient from a log linear model of 0.67 (95% CI 0.32-1.01; p < 0.001), and SMA adding an additional 1.93 days in LOS. For data post-2018, the effect of SMA on LOS was no longer statistically significant.

Conclusions

Utilizing a large dataset, we found a reduced association between SMA and PPC a year following widespread implementation of SMN antisense oligonucleotide therapy, and a statistically significant reduction in LOS in patients with SMA after 2018. This may reflect improved motor outcomes and respiratory mechanics in the new treatment era.