Spinal muscular atrophy (SMA) is a neurodegenerative disorder caused by mutations or deletions in the SMN1 gene. While pediatric trials demonstrate benefits of nusinersen and risdiplam, adult data remain limited. No direct comparisons on outcomes after switching therapies exist. 

Retrospective chart review of 60 adults with SMA undergoing treatment at a single center from 2017–2025, including 20 on active therapy and 40 patients lost to follow-up. Descriptive analyses including longitudinal RULM and HFMSE scores, excluding patients with <2 scores. Baseline was defined as the most recent score before, or first score available within one year of treatment initiation. IRB addendum to interview patients lost-to-follow-up pending.

Average treatment duration 5.7 ± 1.4 years for nusinersen (n=7, IDs: N, M, O, P, Q, R, S), 2.75 +/- 2.06 years for risdiplam (n=2, IDs: A, I) and 7.3 ± 0.5 years for switchers (nusinersen → risdiplam; n=5, IDs: E, C, G, J, K).

Nusinersen: Δ_mean RULM = 1.0 ± 1.7 (Δ/year ≈ +0.19 ± 0.28). Δ_mean HFMSE = +3.2 ± 3.4 (Δ/year ≈ +0.6 ± 0.7).

Risdiplam: Δ_A RULM = +4; Δ_I RULM = 0. 

Switchers: Improvement: Δ_E,RULM= +4, Δ_E,HFMSE= +1 and Δ_G,HFMSE= +6. Decreased scores: Δ_C,RULM= - 2, Δ_J,RULM= - 2, Δ_K,RULM= - 5. Stable: Δ_C,RULM=0.

28% of patient lost to follow resided >30 miles away from the hospital center, compared to 13% active patients, suggesting geographic barriers to sustained care.

Nusinersen and risdiplam were associated with stable/modestly improved motor outcomes in adult SMA patients. A subset of patients showed continued improvement after switching therapies, suggesting potential benefit of sequential treatment. Despite the single-center sample, trends underscore the importance of longitudinal follow-up and addressing barriers to care.