Longitudinal motor trajectories of patients with SMA type 1 after treatment with onasemnogene abeparvovec – UK experience

Topic:

Other

Poster Number: LB457

Author(s):

Vasantha Gowda, MD, Evelina London Children's Hospital, Deborah Ridout, MSc, University College London, London, alex schofield, BSc, Evelina London Children's Hospital, London, mariacristina scoto, PhD, Great Ormond Street Hospital, London, anirban majumdar, university hospital bristol, Bristol, archana murugan, university hospital bristol, bristol, min ong, Sheffield Children's NHS Foundation Trust, Sheffied, mark atherton, sheffield children's nhs foundation trust, sheffield, imelda hughes, royal manchester children's hospital, manchester, gary mccullagh, royal manchester children's hospital, manchester, elizabeth wraige, evelina london children's hospital, london, maria vanegas, evelina london children's hospital, michael eyre, evelina london children's hospital, london, laurent servais, MD, PhD, MDUK Oxford neuromuscular centre, oxford, Giovanni Baranello, Great Ormond Street Hospital, London, francesco muntoni, NIHR great ormond street biomedical research centre, london, SMAREACH consortium, United Kingdom

We collated the longitudinal functional scales assessment data of children with SMA type 1 who received intravenous onasemongene abeparvovec (OA), from the SMAREACH database. 83 patients had baseline and at least one follow-up physiotherapy assessment with one of the five outcome measures of interest: CHOP-INTEND, HINE, RHS, RULM, and WHOM.

Median age at OA infusion was 0.78 years (range: 0.07 to 7.40 years); patients pre-treated with other disease modifying therapies (DMTs (54.2%)) were older (median 2.04 vs. 0.48 years). The duration of pre-treatment with other DMTs ranged from 2-69 months. Duration of follow-up varied from 6-36 months; 74 patients had at least 12-month follow-up and 47 patients had at least 24-month follow-up. Weight at infusion ranged from 3.36-20.2 kg.

CHOP-INTEND scores showed significant increases over time, especially at later follow-ups (15.7-point gain at 24months, p<0.001). Baseline CHOP-INTEND categories (<20, 20-39, 40+) were associated with differing outcome trajectories (interaction p<0.001), with lower baseline score showing greater improvement over time and those patients with higher baseline score remaining stable on average. Patients treated before one year of age had higher scores at baseline and this was maintained through-out follow-up. HINE scores similarly improved over time, with significant gains from baseline at each follow-up (9-point improvement at 30 months, p=0.002). Baseline HINE categories (<2, 2-3, 4+) were associated with differing outcome trajectories (interaction p<0.001), and pre-treated patients maintained higher scores (+3.7 points). Age and weight at infusion were not significant overall. In summary, OA treatment shows positive and sustained effects on motor function (CHOP-INTEND, HINE) over time, with baseline scores and age at infusion providing the highest association with outcome, including those who received pre-treatment with other DMTs. Further correlation between duration of DMT pre-treatment and response to OA is underway.