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Evaluation of Children with SMA Type 1 Under Treatment with Nusinersen within the Expanded Access Program in Germany.
J Neuromuscul Dis 2018; 5(2):135-143JN

Abstract

BACKGROUND

Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by muscle weakness and muscle atrophy. Nusinersen acts as a splicing modifier and has recently been approved for intrathecal treatment of SMA.

OBJECTIVE

Prior to approval, nusinersen was provided to patients with SMA type 1 in Germany within an Expanded Access Program (EAP). In contrast to previous clinical trials, children of different age groups and different stages of the disease were treated with nusinersen.

METHODS

We conducted a prospective, longitudinal data collection of patients treated with nusinersen within the EAP in seven neuromuscular centers in Germany. Standardized assessments including CHOP-INTEND and HINE-2 motor milestones were performed at baseline and 60 and 180 days after start of treatment.

RESULTS

Data from 61 SMA type 1 patients (mean age 21.08 months, range 1-93) were available for analysis. After six months of treatment, 47 children (77.0%) improved by ≥4 points in CHOP INTEND score. Mean change in CHOP INTEND score was 9.0±8.0 points. Nineteen patients (31.1%) improved by ≥2 points in HINE-2 motor milestones. Regression analysis revealed age at onset of treatment as major determinant of change in CHOP INTEND from baseline.

CONCLUSION

When analyzing a broad spectrum of SMA type 1 patients, many children showed an improvement of motor function after six months of treatment with nusinersen, which is generally not expected within the natural course of the disease. Long-term observation and follow-up of patients with later onset types of SMA are crucial to understand the clinical impact of treatment with nusinersen.

Authors+Show Affiliations

Department of Neuropediatrics and Muscle Disorders, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.Department of Neuropediatrics and Muscle Disorders, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.Department of Neuropediatrics and Muscle Disorders, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.Department of Neuropediatrics and Muscle Disorders, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.Department of Neuropediatrics and Muscle Disorders, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.Department of Neuropediatrics, Children's Hospital 1, University of Duisburg-Essen, Essen, Germany.Department of Neuropediatrics, Children's Hospital 1, University of Duisburg-Essen, Essen, Germany.Department of Neuropediatrics, University Children's Hospital Muenster, Muenster, Germany.Departement of Child Neurology, University Hospital Giessen, Justus-Liebig-University, Giessen, Germany.Departement of Child Neurology, University Hospital Giessen, Justus-Liebig-University, Giessen, Germany.Department of Pediatrics, Neuropediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.Department of Pediatrics, Neuropediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.Department of Neuropediatrics, Charité - Universitätsmedizin Berlin, Berlin, Germany.Department of Pediatrics and Neuropediatrics, DRK Klinikum Westend, Berlin, Germany.Department of Neuropediatrics and Muscle Disorders, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29689734

Citation

Pechmann, Astrid, et al. "Evaluation of Children With SMA Type 1 Under Treatment With Nusinersen Within the Expanded Access Program in Germany." Journal of Neuromuscular Diseases, vol. 5, no. 2, 2018, pp. 135-143.
Pechmann A, Langer T, Schorling D, et al. Evaluation of Children with SMA Type 1 Under Treatment with Nusinersen within the Expanded Access Program in Germany. J Neuromuscul Dis. 2018;5(2):135-143.
Pechmann, A., Langer, T., Schorling, D., Stein, S., Vogt, S., Schara, U., ... Kirschner, J. (2018). Evaluation of Children with SMA Type 1 Under Treatment with Nusinersen within the Expanded Access Program in Germany. Journal of Neuromuscular Diseases, 5(2), pp. 135-143. doi:10.3233/JND-180315.
Pechmann A, et al. Evaluation of Children With SMA Type 1 Under Treatment With Nusinersen Within the Expanded Access Program in Germany. J Neuromuscul Dis. 2018;5(2):135-143. PubMed PMID: 29689734.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evaluation of Children with SMA Type 1 Under Treatment with Nusinersen within the Expanded Access Program in Germany. AU - Pechmann,Astrid, AU - Langer,Thorsten, AU - Schorling,David, AU - Stein,Sabine, AU - Vogt,Sibylle, AU - Schara,Ulrike, AU - Kölbel,Heike, AU - Schwartz,Oliver, AU - Hahn,Andreas, AU - Giese,Kerstin, AU - Johannsen,Jessika, AU - Denecke,Jonas, AU - Weiβ,Claudia, AU - Theophil,Manuela, AU - Kirschner,Janbernd, PY - 2018/4/25/pubmed PY - 2018/11/2/medline PY - 2018/4/26/entrez KW - SMArtCARE KW - Spinal muscular atrophy KW - motor function KW - motor milestones KW - nusinersen SP - 135 EP - 143 JF - Journal of neuromuscular diseases JO - J Neuromuscul Dis VL - 5 IS - 2 N2 - BACKGROUND: Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by muscle weakness and muscle atrophy. Nusinersen acts as a splicing modifier and has recently been approved for intrathecal treatment of SMA. OBJECTIVE: Prior to approval, nusinersen was provided to patients with SMA type 1 in Germany within an Expanded Access Program (EAP). In contrast to previous clinical trials, children of different age groups and different stages of the disease were treated with nusinersen. METHODS: We conducted a prospective, longitudinal data collection of patients treated with nusinersen within the EAP in seven neuromuscular centers in Germany. Standardized assessments including CHOP-INTEND and HINE-2 motor milestones were performed at baseline and 60 and 180 days after start of treatment. RESULTS: Data from 61 SMA type 1 patients (mean age 21.08 months, range 1-93) were available for analysis. After six months of treatment, 47 children (77.0%) improved by ≥4 points in CHOP INTEND score. Mean change in CHOP INTEND score was 9.0±8.0 points. Nineteen patients (31.1%) improved by ≥2 points in HINE-2 motor milestones. Regression analysis revealed age at onset of treatment as major determinant of change in CHOP INTEND from baseline. CONCLUSION: When analyzing a broad spectrum of SMA type 1 patients, many children showed an improvement of motor function after six months of treatment with nusinersen, which is generally not expected within the natural course of the disease. Long-term observation and follow-up of patients with later onset types of SMA are crucial to understand the clinical impact of treatment with nusinersen. SN - 2214-3599 UR - https://www.unboundmedicine.com/medline/citation/29689734/Evaluation_of_Children_with_SMA_Type_1_Under_Treatment_with_Nusinersen_within_the_Expanded_Access_Program_in_Germany_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JND-180315 DB - PRIME DP - Unbound Medicine ER -