To evaluate the efficacy and tolerability of nusinersen in real-world settings

Nusinersen, an antisense oligonucleotide enhancing SMN protein production, has been approved for all 5q spinal muscular atrophy (SMA) types including adults with SMA type 2 and 3. We present our 2-year-experience with adult SMA patients under nusinersen.

Patients under nusinersen treatment were included in the study. Demographic data, disease course, functional assessments by HFMSE, outcome, and adverse events were reviewed.

Forty SMA patients who met the appropriate criteria for nusinersen treatment were evaluated. Nine patients who could not complete four loading doses due to lumbar puncture difficulties were excluded. Finally, 31 nusinersen-treated patients (3 patients type 2, rest type 3) were analyzed. The mean age was 34.6 ± 9.9, while mean disease duration was 26.7 ± 11 years. The mean follow-up after the first dose was 25 ± 5.7 months. Ten patients (32%) were ambulatory before the first dose. Mean HFMSE score at baseline and after 4 loading doses were 30.6 ± 17.7 and 35.6 ± 18, respectively. Twenty-six patients (84%) who achieved a 3-point increase compared to baseline HFMSE score after the loading doses were considered as responder to treatment, and the maintenance treatment was initiated. At the last follow-up who continued to maintenance therapy, mean HFMSE score increase was 5.88 ± 3.07. All ambulatory patients demonstrated improvement in 6MWT No adverse effect was demonstrated except post-lumbar puncture headache, injection site pain and mild proteinuria. 

Intrathecal nusinersen can be safely delivered in adult SMA patients. The drop-out rate due to lumbar puncture and the efficacy of nusinersen are consistent with the literature. Overall, nusinersen was well tolerated and effective in most of the patients. Clinical data for nusinersen in adults is sparse, therefore long-term studies with larger population are needed.