Real-world use of botulinum toxin-A for post-stroke spasticity in the Netherlands: a retrospective claims study
DOI:
https://doi.org/10.2340/jrm.v58.43952Keywords:
botulinum toxin A, post-stroke spasticity, epidemiology, observational study, claims dataAbstract
Objective: The aim of this observational study was to describe the real-world use of botulinum toxin-A in patients with a stroke in the Netherlands.
Methods: This study used longitudinal insurance claims data between 2012 and 2016 with 30% nationwide coverage and included patients with both stroke-related and botulinum toxin-A claims. All analyses were descriptive and displayed as summary statistics.
Results: 60,222 patients with a stroke were identified, of whom 18,141 (30.1%) were treated in a rehabilitation centre or hospital and 1.7% (1,036 patients) were treated with botulinum toxin-A. A total of 2,855 botulinum toxin-A claims from 890 patients were included in the analysis (1.5% of all patients in the database). Mean age was 63.4 (SD ± 14.0) years at index injection cycle, with a median follow-up of 3.7 years (interquartile range [IQR] 2.2–4.5 years). Patients received up to 16 injection cycles with a median of 2 injection cycles (IQR 1–5 cycles). The median Time-To-Next-Injection-Cycle was 17 weeks (IQR 13–25 weeks). The total number of injection cycles was 604 for abobotulinumtoxinA (22.1%) and 2,251 (78.8%) for onabotulinumtoxinA. Doses per cycle ranged from 200–660 for abobotulinumtoxinA and 101–400 units for onabotulinumtoxinA.
Discussion: Claims data from a national healthcare insurance fund in the Netherlands showed that only 1.7% of patients with post-stroke spasticity received botulinum toxin-A. Botulinum toxin-A treatment doses and intervals varied widely across patients and most patients received only 1 or 2 botulinum toxin-A injection cycles. Our results suggest undertreatment of spasticity with botulinum toxin-A and suboptimal treatment adherence in Dutch clinical practice.
Downloads
References
G. B. D. Stroke Collaborators. Global, regional, and national burden of stroke and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol 2021; 20: 795–820.
https://doi.org/10.1016/S1474-4422(21)00252-0 DOI: https://doi.org/10.1016/S1474-4422(21)00252-0
Koop Y, Wimmers RH, Rutten FH, Bots ML, Vaartjes I. Cardiovascular diseases in the Dutch general practice (Dutch: Hart- en vaatziekten in de Nederlandse huisartsenpraktijk). 2024 [cited 2024] Available from: https://www.hartenvaatcijfers.nl/jaarcijfers/basiscijfers-beroerte-e5487
Zeng H, Chen J, Guo Y, Tan S. Prevalence and risk factors for spasticity after stroke: a systematic review and meta-analysis. Front Neurol 2020; 11: 616097.
https://doi.org/10.3389/fneur.2020.616097 DOI: https://doi.org/10.3389/fneur.2020.616097
Chen S. Clinical uses of botulinum neurotoxins: current indications, limitations and future developments. Toxins (Basel) 2012; 4: 913–939.
https://doi.org/10.3390/toxins4100913 DOI: https://doi.org/10.3390/toxins4100913
Bavikatte G, Subramanian G, Ashford S, Allison R, Hicklin D. Early identification, intervention and management of post-stroke spasticity: expert consensus recommendations. J Cent Nerv Syst Dis 2021; 13: 11795735211036576.
https://doi.org/10.1177/11795735211036576 DOI: https://doi.org/10.1177/11795735211036576
Watkins CL, Leathley MJ, Gregson JM, Moore AP, Smith TL, Sharma AK. Prevalence of spasticity post stroke. Clin Rehabil 2002; 16: 515–522.
https://doi.org/10.1191/0269215502cr512oa DOI: https://doi.org/10.1191/0269215502cr512oa
Wissel J, Manack A, Brainin M. Toward an epidemiology of poststroke spasticity. Neurology 2013; 80: S13–19.
https://doi.org/10.1212/WNL.0b013e3182762448 DOI: https://doi.org/10.1212/WNL.0b013e3182762448
Dutch Association of Rehabilitation Physicians [Nederlandse Vereniging van Revalidatieartsen]. National guideline cerebral and/or spinal spasticity [Richtlijn cerebrale en/of spinale spasticiteit]; 2016. Available from https://richtlijnendatabase.nl/richtlijn/cerebrale_en_of_spinale_spasticiteit/cerebrale_en_of_spinale_spasticiteit_-_startpagina.html.
Royal College of Physicians. Spasticity in adults: management using botulinum toxin. National guidelines; 2018. Avalable from https://www.rcp.ac.uk/media/i1ijs0tm/spasticity-in-adults_final-version_march-2019.pdf
Wissel J, Ri S. Assessment, goal setting, and botulinum neurotoxin a therapy in the management of post-stroke spastic movement disorder: updated perspectives on best practice. Expert Rev Neurother 2022; 22: 27–42.
https://doi.org/10.1080/14737175.2021.2021072 DOI: https://doi.org/10.1080/14737175.2021.2021072
Simpson DM, Hallett M, Ashman EJ, Comella CL, Green MW, Gronseth GS, et al. Practice guideline update summary: Botulinum neurotoxin for the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 2016; 86: 1818–1826.
https://doi.org/10.1212/WNL.0000000000002560 DOI: https://doi.org/10.1212/WNL.0000000000002560
Canadian Agency for Drugs and Technologies in Health (CADTH). Pharmacoeconomic review report: AbobotulinumtoxinA (Dysport Therapeutic): (Ipsen Biopharmaceuticals Canada, Inc.): Indication: For the symptomatic treatment of focal spasticity affecting the upper limbs in adults; 2017. Available from https://www.ncbi.nlm.nih.gov/books/NBK534668/
Turner-Stokes L, Jacinto J, Fheodoroff K, Brashear A, Maisonobe P, Lysandropoulos A, et al. Longitudinal goal attainment with integrated upper limb spasticity management including repeat injections of botulinum toxin A: findings from the prospective, observational Upper Limb International Spasticity (ULIS-III) cohort study. J Rehabil Med 2021; 53: jrm00157.
https://doi.org/10.2340/16501977-2801 DOI: https://doi.org/10.2340/16501977-2801
Rosales RL, Kong KH, Goh KJ, Kumthornthip W, Mok VC, Delgado-De Los Santos MM, et al. Botulinum toxin injection for hypertonicity of the upper extremity within 12 weeks after stroke: a randomized controlled trial. Neurorehabil Neural Repair 2012; 26: 812–821.
https://doi.org/10.1177/1545968311430824 DOI: https://doi.org/10.1177/1545968311430824
Gracies JM, O’Dell M, Vecchio M, Hedera P, Kocer S, Rudzinska-Bar M, et al. Effects of repeated abobotulinumtoxinA injections in upper limb spasticity. Muscle Nerve 2018; 57: 245–254.
https://doi.org/10.1002/mus.25721 DOI: https://doi.org/10.1002/mus.25721
Gracies JM, Esquenazi A, Brashear A, Banach M, Kocer S, Jech R, et al. Efficacy and safety of abobotulinumtoxinA in spastic lower limb: randomized trial and extension. Neurology 2017; 89: 2245–2253.
https://doi.org/10.1212/WNL.0000000000004687 DOI: https://doi.org/10.1212/WNL.0000000000004687
Gracies JM, Brashear A, Jech R, McAllister P, Banach M, Valkovic P, et al. Safety and efficacy of abobotulinumtoxinA for hemiparesis in adults with upper limb spasticity after stroke or traumatic brain injury: a double-blind randomised controlled trial. Lancet Neurol 2015; 14: 992–1001.
https://doi.org/10.1016/S1474-4422(15)00216-1 DOI: https://doi.org/10.1016/S1474-4422(15)00216-1
Wein T, Esquenazi A, Jost WH, Ward AB, Pan G, Dimitrova R. OnabotulinumtoxinA for the treatment of poststroke distal lower limb spasticity: a randomized trial. PM R 2018; 10: 693–703.
https://doi.org/10.1016/j.pmrj.2017.12.006 DOI: https://doi.org/10.1016/j.pmrj.2017.12.006
Rosales RL, Efendy F, Teleg ES, Delos Santos MM, Rosales MC, Ostrea M, et al. Botulinum toxin as early intervention for spasticity after stroke or non-progressive brain lesion: a meta-analysis. J Neurol Sci 2016; 371: 6–14.
https://doi.org/10.1016/j.jns.2016.10.005 DOI: https://doi.org/10.1016/j.jns.2016.10.005
Turner-Stokes L, Fheodoroff K, Jacinto J, Maisonobe P. Results from the Upper Limb International Spasticity Study-II (ULISII): a large, international, prospective cohort study investigating practice and goal attainment following treatment with botulinum toxin A in real-life clinical management. BMJ Open 2013; 3: e002771.
https://doi.org/10.1136/bmjopen-2013-002771 DOI: https://doi.org/10.1136/bmjopen-2013-002771
Turner-Stokes L, Jacinto J, Fheodoroff K, Brashear A, Maisonobe P, Lysandropoulos A, et al. Assessing the effectiveness of upper-limb spasticity management using a structured approach to goal-setting and outcome measurement: first cycle results from the ULIS-III Study. J Rehabil Med 2021; 53: jrm00133.
https://doi.org/10.2340/16501977-2770 DOI: https://doi.org/10.2340/16501977-2770
Egen-Lappe V, Koster I, Schubert I. Incidence estimate and guideline-oriented treatment for post-stroke spasticity: an analysis based on German statutory health insurance data. Int J Gen Med 2013; 6: 135–144.
https://doi.org/10.2147/IJGM.S36030 DOI: https://doi.org/10.2147/IJGM.S36030
Esquenazi A, Francisco GE, Feng W, Baricich A, Gallien P, Fanning K, et al. Real-world adherence to onabotulinumtoxinA treatment for spasticity: insights from the ASPIRE Study. Arch Phys Med Rehabil 2021; 102: 2172–2184 e2176.
https://doi.org/10.1016/j.apmr.2021.06.008 DOI: https://doi.org/10.1016/j.apmr.2021.06.008
Hull M, Anupindi VR, DeKoven M, He J, Bouchard J. Botulinum toxin utilization, treatment patterns, and healthcare costs among patients with spasticity or cervical dystonia in the US. Adv Ther 2023; 40: 3986–4003.
https://doi.org/10.1007/s12325-023-02563-5 DOI: https://doi.org/10.1007/s12325-023-02563-5
Woo J, Mas MF, Zhang J, Wong B, Stampas A, Francisco GE, et al. Real-world analysis of botulinum toxin (BoNT) injections in post-stroke spasticity: higher doses of BoNT and longer intervals in the early-start group. J Neurol Sci 2021; 425: 117449.
https://doi.org/10.1016/j.jns.2021.117449 DOI: https://doi.org/10.1016/j.jns.2021.117449
Levy J, Karam P, Forestier A, Loze JY, Bensmail D. Botulinum toxin use in patients with post-stroke spasticity: a nationwide retrospective study from France. Front Neurol 2023; 14: 1245228.
https://doi.org/10.3389/fneur.2023.1245228 DOI: https://doi.org/10.3389/fneur.2023.1245228
Rakers F, Weise D, Hamzei F, Musleh R, Schwab M, Jacob J, et al. The incidence and outpatient medical care of patients with post-stroke spasticity. Dtsch Arztebl Int 2023; 120: 284–285.
https://doi.org/10.3238/arztebl.m2023.0004 DOI: https://doi.org/10.3238/arztebl.m2023.0004
Potempa C, Thiem H, Rychlik R, Wissel J, Ebke M, Rebscher H, et al. Zur Versorgungslage von Patienten mit spastischer Bewegungsstöring in Deutschland. Monitor Versorgungsforschung 2019; 03: 65–72.
https://doi.org/10.24945/MVF.03.19.1866-0533.2149 DOI: https://doi.org/10.24945/MVF.03.19.1866-0533.2149
Völkel L, Rebscher H, Rychlik R. Versorgungssituation von Patient:innen mit spastischer Bewegungsstörung in stationären Pflegeeinrichtungen in Deutschland. Monitor Versorgungsforschung 2022; 4: 81–87.
https://doi.org/10.24945/MVF.04.22.1866-0533.2430 DOI: https://doi.org/10.24945/MVF.04.22.1866-0533.2430
Visser-Meily JMA, Achterberg WP. The rehabilition landscape is changing: the importance of collaboration [Het revalidatielandschap verandert: belang van samenwerken]. Dutch J Rehab Med [Nederlands Tijdschrift voor Revalidatiegeneeskunde] 2021: 18–23.
Nederlandse Huisartsen Genootschap (NHG). NHG-Standaard Beroerte [NHG-Standard Stroke]; 2022. Available from https://richtlijnen.nhg.org/standaarden/beroerte.
Koninklijk Nederlands Genootschap van Fysiotherapie (KNGF). KNGF-richtlijn Beroerte [KNGF-guideline Stroke]; 2014. Available from https://www.kennisplatformfysiotherapie.nl/richtlijnen/beroerte/hoofdstuk-a-en-b/
van Eeden M, van Heugten C, van Mastrigt GA, van Mierlo M, Visser-Meily JM, Evers SM. The burden of stroke in the Netherlands: estimating quality of life and costs for 1 year poststroke. BMJ Open 2015; 5: e008220.
https://doi.org/10.1136/bmjopen-2015-008220 DOI: https://doi.org/10.1136/bmjopen-2015-008220
Nederlandse Zorgautoriteit (NZa). Wilt u een add-on geneesmiddel aanvragen? 2024 [cited Dec 18 2024]. Available from: https://www.nza.nl/zorgsectoren/geneesmiddelenzorg/registreren-en-declareren-in-de-msz/wilt-u-een-add-on-geneesmiddel-aanvragen.
GIP Open Data. Reimbursement per user 2018–2022 for ATC subgroup M03AX01: Botulinum toxin [Vergoeding per gebruiker 2018–2022 voor ATC-subgroep M03AX01: Botuline toxine]; 2023. Available from: https://www.gipdatabank.nl/databank?infotype=d&label=00-totaal&tabel_d_00-totaal=B_01-basis&geg=vg&spec=vg_gebr&item=M03AX01
Kerstens H, Satink T, Nijkrake MJ, De Swart BJM, Nijhuis-van der Sanden MWG, Van der Wees PJ, et al. Experienced consequences of spasticity and effects of botulinum toxin injections: a qualitative study amongst patients with disabling spasticity after stroke. Disabil Rehabil 2021; 43: 3688–3695.
https://doi.org/10.1080/09638288.2020.1746843 DOI: https://doi.org/10.1080/09638288.2020.1746843
Kerstens H, Nijkrake MJ, De Swart BJM, Nijhuis-van der Sanden RWG, Vos-van de Hulst M, Bos GJ, et al. Online monitoring of focal spasticity treatment with botulinum toxin in people with chronic stroke or hereditary spastic paraplegia: a feasibility study. J Rehabil Med 2023; 55: jrm00383.
https://doi.org/10.2340/jrm.v55.6572 DOI: https://doi.org/10.2340/jrm.v55.6572
Zorgwijzer. Figures on healthcare insurances in the Netherlands [Cijfers zorgverzekering]; 2023 Available from: https://www.zorgwijzer.nl/faq/cijfers-zorgverzekering#:~:text=Ieder%20jaar%20krijgen%20Nederlanders%20met,Overstappercentage%20per%20jaar.&text=Voor%202021%2F2022%20zijn%20er,miljoen%20wisselingen%20van%20zorgverzekering%20geweest
Downloads
Additional Files
Published
How to Cite
License
Copyright (c) 2026 Max van Wijk, Mary Verhoeven, Thom S. Lysen, Hanne van Ballegooijen, Alexander C.H. Geurts
This work is licensed under a Creative Commons Attribution 4.0 International License.
All digitalized JRM contents is available freely online. The Foundation for Rehabilitation Medicine owns the copyright for all material published until volume 40 (2008), as from volume 41 (2009) authors retain copyright to their work and as from volume 49 (2017) the journal has been published Open Access, under CC-BY-NC licences (unless otherwise specified). The CC-BY-NC licenses allow third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material for non-commercial purposes, provided proper attribution to the original work.
From 2024, articles are published under the CC-BY licence. This license permits sharing, adapting, and using the material for any purpose, including commercial use, with the condition of providing full attribution to the original publication.
