Improved upper limb function in non-ambulant children with SMA type 2 and 3 during nusinersen treatment: a prospective 3-years SMArtCARE registry study

TY - JOUR

T1 - Improved upper limb function in non-ambulant children with SMA type 2 and 3 during nusinersen treatment: a prospective 3-years SMArtCARE registry study

AU - Pechmann, Astrid

AU - Behrens, Max

AU - Dörnbrack, Katharina

AU - Tassoni, Adrian

AU - Wenzel, Franziska

AU - Stein, Sabine

AU - Vogt, Sibylle

AU - Zöller, Daniela

AU - Bernert, Günther

AU - Hagenacker, Tim

AU - Schara-Schmidt, Ulrike

AU - Walter, Maggie C

AU - Bertsche, Astrid

AU - Vill, Katharina

AU - Baumann, Matthias

AU - Baumgartner, Manuela

AU - Cordts, Isabell

AU - Eisenkölbl, Astrid

AU - Flotats-Bastardas, Marina

AU - Friese, Johannes

AU - Günther, René

AU - Hahn, Andreas

AU - Horber, Veronka

AU - Husain, Ralf A

AU - Illsinger, Sabine

AU - Jahnel, Jörg

AU - Johannsen, Jessika

AU - Köhler, Cornelia

AU - Kölbel, Heike

AU - Müller, Monika

AU - von Moers, Arpad

AU - Schwerin-Nagel, Annette

AU - Reihle, Christof

AU - Schlachter, Kurt

AU - Schreiber, Gudrun

AU - Schwartz, Oliver

AU - Smitka, Martin

AU - Steiner, Elisabeth

AU - Trollmann, Regina

AU - Weiler, Markus

AU - Weiß, Claudia

AU - Wiegand, Gert

AU - Wilichowski, Ekkehard

AU - Ziegler, Andreas

AU - Lochmüller, Hanns

AU - Kirschner, Janbernd

AU - SMArtCARE study group

AU - Weiss, Deike

N1 - © 2022. The Author(s).

PY - 2022/10/23

Y1 - 2022/10/23

N2 - BACKGROUND: The development and approval of disease modifying treatments have dramatically changed disease progression in patients with spinal muscular atrophy (SMA). Nusinersen was approved in Europe in 2017 for the treatment of SMA patients irrespective of age and disease severity. Most data on therapeutic efficacy are available for the infantile-onset SMA. For patients with SMA type 2 and type 3, there is still a lack of sufficient evidence and long-term experience for nusinersen treatment. Here, we report data from the SMArtCARE registry of non-ambulant children with SMA type 2 and typen 3 under nusinersen treatment with a follow-up period of up to 38 months.METHODS: SMArtCARE is a disease-specific registry with data on patients with SMA irrespective of age, treatment regime or disease severity. Data are collected during routine patient visits as real-world outcome data. This analysis included all non-ambulant patients with SMA type 2 or 3 below 18 years of age before initiation of treatment. Primary outcomes were changes in motor function evaluated with the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM).RESULTS: Data from 256 non-ambulant, pediatric patients with SMA were included in the data analysis. Improvements in motor function were more prominent in upper limb: 32.4% of patients experienced clinically meaningful improvements in RULM and 24.6% in HFMSE. 8.6% of patients gained a new motor milestone, whereas no motor milestones were lost. Only 4.3% of patients showed a clinically meaningful worsening in HFMSE and 1.2% in RULM score.CONCLUSION: Our results demonstrate clinically meaningful improvements or stabilization of disease progression in non-ambulant, pediatric patients with SMA under nusinersen treatment. Changes were most evident in upper limb function and were observed continuously over the follow-up period. Our data confirm clinical trial data, while providing longer follow-up, an increased number of treated patients, and a wider range of age and disease severity.

AB - BACKGROUND: The development and approval of disease modifying treatments have dramatically changed disease progression in patients with spinal muscular atrophy (SMA). Nusinersen was approved in Europe in 2017 for the treatment of SMA patients irrespective of age and disease severity. Most data on therapeutic efficacy are available for the infantile-onset SMA. For patients with SMA type 2 and type 3, there is still a lack of sufficient evidence and long-term experience for nusinersen treatment. Here, we report data from the SMArtCARE registry of non-ambulant children with SMA type 2 and typen 3 under nusinersen treatment with a follow-up period of up to 38 months.METHODS: SMArtCARE is a disease-specific registry with data on patients with SMA irrespective of age, treatment regime or disease severity. Data are collected during routine patient visits as real-world outcome data. This analysis included all non-ambulant patients with SMA type 2 or 3 below 18 years of age before initiation of treatment. Primary outcomes were changes in motor function evaluated with the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM).RESULTS: Data from 256 non-ambulant, pediatric patients with SMA were included in the data analysis. Improvements in motor function were more prominent in upper limb: 32.4% of patients experienced clinically meaningful improvements in RULM and 24.6% in HFMSE. 8.6% of patients gained a new motor milestone, whereas no motor milestones were lost. Only 4.3% of patients showed a clinically meaningful worsening in HFMSE and 1.2% in RULM score.CONCLUSION: Our results demonstrate clinically meaningful improvements or stabilization of disease progression in non-ambulant, pediatric patients with SMA under nusinersen treatment. Changes were most evident in upper limb function and were observed continuously over the follow-up period. Our data confirm clinical trial data, while providing longer follow-up, an increased number of treated patients, and a wider range of age and disease severity.

KW - Child

KW - Humans

KW - Prospective Studies

KW - Spinal Muscular Atrophies of Childhood/drug therapy

KW - Muscular Atrophy, Spinal

KW - Registries

KW - Disease Progression

KW - Upper Extremity

U2 - 10.1186/s13023-022-02547-8

DO - 10.1186/s13023-022-02547-8

M3 - SCORING: Journal article

C2 - 36274155

VL - 17

JO - ORPHANET J RARE DIS

JF - ORPHANET J RARE DIS

SN - 1750-1172

IS - 1

M1 - 384

ER -