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. 2021 Mar;8(3):548-557.
doi: 10.1002/acn3.51276. Epub 2021 Feb 6.

Type I SMA "new natural history": long-term data in nusinersen-treated patients

Marika Pane  1   2 , Giorgia Coratti  1   2 , Valeria A Sansone  3 , Sonia Messina  4 , Michela Catteruccia  5 , Claudio Bruno  6 , Maria Sframeli  4 , Emilio Albamonte  3 , Marina Pedemonte  6 , Adele D'Amico  5 , Chiara Bravetti  2 , Beatrice Berti  2 , Concetta Palermo  2 , Daniela Leone  2 , Giorgia Brigati  6 , Paola Tacchetti  6 , Francesca Salmin  3 , Roberto De Sanctis  2 , Simona Lucibello  1   2 , Maria Carmela Pera  1   2 , Marco Piastra  7 , Orazio Genovese  7 , Enrico Bertini  5 , Gianluca Vita  4 , Francesco Danilo Tiziano  8 , Eugenio Mercuri  1   2 ; Italian EAP Working Group
Affiliations

Type I SMA "new natural history": long-term data in nusinersen-treated patients

Marika Pane et al. Ann Clin Transl Neurol. 2021 Mar.

Abstract

Objective: The aim of this paper was to report the 2-year follow-up in type I patients treated with Nusinersen and to assess whether possible changes in motor function are related to the subtype, age, or SMN2 copy number.

Methods: Sixty-eight patients, with ages ranging from 0.20 to 15.92 years (mean: 3.96; standard deviation: +3.90) were enrolled in the study. All patients were assessed using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) and the developmental section of the Hammersmith Infant Neurological Examination (HINE-2) at the time they started treatment and 12 and 24 months after that.

Results: For both CHOP and HINE-2 repeated measures analysis of variance showed a significant difference (P < 0.001) between baseline and 12 months, 12 months and 24 months, and baseline and 24-month scores for the whole group. When age subgroups (<210 days, <2 years, 2-4 years, 5-11 years, 12-18 years) were considered, on the CHOP INTEND the difference was significant between baseline and 24 months in all age subgroups. On the HINE-2, the difference between baseline and 24 months was significant in all the subgroups before the age of 4 years. Age was predictive of changes on both scales (P < 0.05), whereas SMN2 copy number and decimal classification were not.

Interpretation: Our results suggest that some improvement of motor function can be observed even after the first year of treatment. This is more obvious in the infants treated in the first 2 years but some improvement can also be found in older children.

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Conflict of interest statement

GC, RDS, MP, SM, ADA, EB, VAS, CB, and EM has been a consultant for BIOGEN S.R.L. which owns patent rights to nusinersen that was used in this study.

Figures

Figure 1
Figure 1
Enrollment flowchart from baseline paper to this study. 9
Figure 2
Figure 2
CHOP INTEND individual trajectories over 24 months. (A) <210 days (B) <2 years (C) 2–4 years (D) >4 years. Key to figure: Red line: 1.1; Green line: 1.5; Blue line: 1.9.
Figure 3
Figure 3
HINE‐2 individual trajectories over 24 months. (A) <210 days (B) <2 years (C) 2–4 years (D) >4 years. Key to figure: Red line: 1.1; Green line: 1.5; Blue line: 1.9. Dashed line: Sitters; Plain line: Nonsitter. Red asterisks: patients who achieved sitting position 24 months from treatment initiation.
Figure 4
Figure 4
Individual details on sitting position from baseline to 24 months. ○: sitter •: nonsitter →: transferred; +:deceased; ­: nusinersen discontinuation; *: enrollment in a clinical trial.
Figure 5
Figure 5
Individual details on ventilator status from baseline to 24 months. ○: Spontaneous breathing or NIV <16 h; •: NIV ≥16 h or tracheostomy; →: transferred; +:deceased; ­: nusinersen discontinuation; *: enrollment in a clinical trial.
See this image and copyright information in PMC

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