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CNS & Neurological Disorders - Drug Targets

Author(s): Riccardo Marvulli*, Maurizio Ranieri, Laura Belinda Rizzo, Francesco Marra, Giancarlo Ianieri and Marisa Megna

DOI: 10.2174/1871527321666220630154404

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Clinical Onset of Action of Incobotulinum Toxin A Preparation

Page: [916 - 923] Pages: 8

  • * (Excluding Mailing and Handling)

Abstract

Background: Many studies in vitro compared the onset of action, maximum efficacy, and duration of botulinum toxin type A (BoNT/A) preparations.

Objective: In this study, we analyzed the onset of action of BoNT/A preparation free of complexing proteins in patients with upper limb spasticity post stroke up to 30 days after treatment.

Methods: 75 patients affected by Biceps Brachii spasticity were enrolled. Outcome measures were instrumental muscle tone modification (myometric measurement), improvement of Modified Ashworth Scale (MAS), improvement of elbow’s passive extension, and improvement of compound muscle action potential (cMAP) evaluated by electroneurography. We analyzed data at t0 (pre-injection), t1 (1 day after), t2 (7 days after), t3 (14 days after), and t4 (30 days after).

Results: All measurements decreased at t2, t3, and t4 with initial improvement at t2 and maximum improvement at t4; no statistical difference at t1 was found.

Conclusion: This study demonstrated the onset of Incobotulinumtoxin A efficacy started after 7 days; this rapid action and efficacy of BoNT/A preparation could improve an intensive rehabilitation program after some days post-injection. Early clinical onset of action could be by the absence of complexing proteins in the preparation.

Keywords: Spasticity, botulinum toxin type A, stroke, electroneurography, myometric measurement, physiotherapy

Graphical Abstract

[1]
Pellett S, Tepp WH, Whitemarsh RCM, Bradshaw M, John-son EA. In vivo onset and duration of action varies for Botulinum neurotoxin A subtypes 1-5. Toxicon 2015; 107: 37-42.
[http://dx.doi.org/10.1016/j.toxicon.2015.06.021]
[2]
Simpson DM, Blitzer A, Brashear A, et al. Assessment: Botulinum neurotoxin for the treatment of movement disorders (an evidence-based review): Report of the therapeutics and technology assessment subcommittee of the American academy of neurology. Neurology 2008; 70(19): 1699-706.
[http://dx.doi.org/10.1212/01.wnl.0000311389.26145.95] [PMID: 18458230]
[3]
Wissel J, Ward AB, Erztgaard P, et al. European consensus table on the use of botulinum toxin type A in adult spasticity. J Rehabil Med 2009; 41(1): 13-25.
[http://dx.doi.org/10.2340/16501977-0303] [PMID: 19197564]
[4]
Montal M. Botulinum neurotoxin: A marvel of protein design. Annu Rev Biochem 2010; 79: 591-617.
[http://dx.doi.org/10.1146/annurev.biochem.051908.125345] [PMID: 20233039]
[5]
Rummel A. Double receptor anchorage of botulinum neurotoxins accounts for their exquisite neurospecificity. Curr Top Microbiol Immunol 2013; 364: 61-90.
[http://dx.doi.org/10.1007/978-3-662-45790-0_4] [PMID: 23239349]
[6]
Fischer A, Nakai Y, Eubanks LM, et al. Bimodal modulation of the botulinum neurotoxin protein-conducting channel. Proc Natl Acad Sci USA 2009; 106(5): 1330-5.
[http://dx.doi.org/10.1073/pnas.0812839106] [PMID: 19164566]
[7]
Pirazzini M, Azarnia Tehran D, Zanetti G, et al. Thioredoxin and its reductase are present on synaptic vesicles, and their inhibition prevents the paralysis induced by botulinum neurotoxins. Cell Rep 2014; 8(6): 1870-8.
[http://dx.doi.org/10.1016/j.celrep.2014.08.017] [PMID: 25220457]
[8]
Mastromauro L, Trerotoli P, Romanelli E, Marvulli R, Ianieri G. Incobotulinumtoxina (Xeomin®) versus onabotulinumtoxina (Botox®): Evaluation of clinical onset of action with rating scales and electroneurography. Int J Neurorehabilitation Eng 2015; 2: 4.
[http://dx.doi.org/10.4172/2376-0281.1000182]
[9]
Dressler D. Five-year experience with incobotulinumtoxinA (Xeomin®): The first botulinum toxin drug free of complexing proteins. Eur J Neurol 2012; 19(3): 385-9.
[http://dx.doi.org/10.1111/j.1468-1331.2011.03559.x] [PMID: 22035051]
[10]
Eisele KH, Fink K, Vey M, Taylor HV. Studies on the dissociation of botulinum neurotoxin type A complexes. Toxicon 2011; 57(4): 555-65.
[http://dx.doi.org/10.1016/j.toxicon.2010.12.019] [PMID: 21195107]
[11]
DasGupta BR, Boroff DA. Separation of toxin and hemagglutinin from crystalline toxin of Clostridium botulinum type A by anion exchange chromatography and determination of their dimensions by gel filtration. J Biol Chem 1968; 243(5): 1065-72.
[http://dx.doi.org/10.1016/S0021-9258(18)93623-9] [PMID: 4867941]
[12]
Dasgupta BR, Boroff DA, Cheong K. Cation-exchange chromatography of Clostridium botulinum type A toxin on amber-lite IRC-50 resin at pH 5.55. Biochim Biophys Acta 1968; 168(3): 522-31.
[http://dx.doi.org/10.1016/0005-2795(68)90185-2] [PMID: 4973552]
[13]
Sugii S, Sakaguchi G. Molecular construction of Clostridium botulinum type A toxins. Infect Immun 1975; 12(6): 1262-70.
[http://dx.doi.org/10.1128/iai.12.6.1262-1270.1975] [PMID: 54335]
[14]
Chung ME, Song DH, Park JH. Comparative study of biological activity of four botulinum toxin type A preparations in mice. Dermatol Surg 2013; 39(1 Pt 2): 155-64.
[http://dx.doi.org/10.1111/dsu.12071] [PMID: 23301819]
[15]
Carli L, Montecucco C, Rossetto O. Assay of diffusion of different botulinum neurotoxin type a formulations injected in the mouse leg. Muscle Nerve 2009; 40(3): 374-80.
[http://dx.doi.org/10.1002/mus.21343] [PMID: 19618426]
[16]
Kim SH, Kim SB, Yang GH, Rhee CH. Mouse compound muscle action potential assay: An alternative method to conduct the LD₅₀ botulinum toxin type A potency test. Toxicon 2012; 60(3): 341-7.
[http://dx.doi.org/10.1016/j.toxicon.2012.05.003] [PMID: 22613167]
[17]
Eleopra R, Tugnoli V, Quatrale R, Rossetto O, Montecucco C. Different types of botulinum toxin in humans. Mov Disord 2004; 19 (Suppl. 8): S53-9.
[http://dx.doi.org/10.1002/mds.20010] [PMID: 15027055]
[18]
Li F, Wu Y, Li X. Test-retest reliability and inter-rater reliability of the Modified Tardieu Scale and the Modified Ash-worth Scale in hemiplegic patients with stroke. Eur J Phys Rehabil Med 2014; 50(1): 9-15.
[PMID: 24309501]
[19]
Ohn SH, Yoo WK, Kim DY, et al. Measurement of synergy and spasticity during functional movement of the post-stoke hemiplegic upper limb. J Electromyogr Kinesiol 2013; 23(2): 501-7.
[http://dx.doi.org/10.1016/j.jelekin.2012.10.001] [PMID: 23146551]
[20]
Hamjian JA, Walker FO. Serial neurophysiological studies of intramuscular botulinum-A toxin in humans. Muscle Nerve 1994; 17(12): 1385-92.
[http://dx.doi.org/10.1002/mus.880171207] [PMID: 7969239]
[21]
Torii Y, Goto Y, Takahashi M, et al. Quantitative determination of biological activity of botulinum toxins utilizing compound muscle action potentials (CMAP), and comparison of neuromuscular transmission blockage and muscle flaccidity among toxins. Toxicon 2010; 55(2-3): 407-14.
[http://dx.doi.org/10.1016/j.toxicon.2009.09.005] [PMID: 19778548]
[22]
Preston DC, Shapiro BE. Electromyography and neuromuscular disorders. In:Clinical-Electrophysiologic Correletions. Elsevier Saunders 2013.
[23]
Rossetto O, Pirazzini M, Montecucco C. Botulinum neurotoxins: Genetic, structural and mechanistic insights. Nat Rev Microbiol 2014; 12(8): 535-49.
[http://dx.doi.org/10.1038/nrmicro3295] [PMID: 24975322]
[24]
Rummel A. The long journey of botulinum neurotoxins into the synapse. Toxicon 2015; 107: 9-24.
[http://dx.doi.org/10.1016/j.toxicon.2015.09.009]
[25]
Pirazzini M, Rossetto O, Eleopra R, Montecucco C. Botulinum neurotoxins: Biology, pharmacology, and toxicology. Pharmacol Rev 2017; 69(2): 200-35.
[http://dx.doi.org/10.1124/pr.116.012658] [PMID: 28356439]
[26]
Dressler D. Clinical applications of botulinum toxin. Curr Opinion Microbiol 2012; 15(3): 325-5.
[http://dx.doi.org/10.1016/j.mib.2012.05.012]
[27]
Hallet M. Explanation of timing of botulinum neurotoxin effects, onset and duration and clinical ways of influencing them. Toxicon 2015; 107: 64-7.
[http://dx.doi.org/10.1016/j.toxicon.2015.07.013]
[28]
Gracies JM. Physiological effects of botulinum toxin in spasticity. Mov Disord 2004; 19 (Suppl. 8): S120-8.
[http://dx.doi.org/10.1002/mds.20065] [PMID: 15027064]
[29]
Rossetto O, Pirazzini M, Fabris F, Montecucco C. Botulinum neurotoxins: Mechanism of action. Handb Exp Pharmacol 2021; 263: 35-47.
[http://dx.doi.org/10.1007/164_2020_355] [PMID: 32277300]
[30]
Carli L, Montecucco C, Rossetto O. Assay of diffusion of different botulinum neurotoxin type A formulation injected in the mouse leg. In: Wiley Inter Science 2009.
[http://dx.doi.org/10.1002/mus.21343]
[31]
Chen F, Kuziemko GM, Stevens RC. Biophysical characterization of the stability of the 150-kilodalton botulinum toxin, the nontoxic component, and the 900-kilodalton botulinum toxin complex species. Infect Immun 1998; 66(6): 2420-5.
[http://dx.doi.org/10.1128/IAI.66.6.2420-2425.1998] [PMID: 9596697]
[32]
Sharma SK, Fu FN, Singh BR. Molecular properties of a hemagglutinin purified from type A Clostridium botulinum. J Protein Chem 1999; 18(1): 29-38.
[http://dx.doi.org/10.1023/A:1020691215056] [PMID: 10071926]
[33]
Schiavo G, Rossetto O, Montecucco C. Clostridial neurotoxins as tools to investigate the molecular events of neurotransmitter release. Semin Cell Biol 1994; 5(4): 221-9.
[http://dx.doi.org/10.1006/scel.1994.1028] [PMID: 7994006]
[34]
Colasante C, Rossetto O, Morbiato L, Pirazzini M, Molgó J, Montecucco C. Botulinum neurotoxin type A is internalized and translocated from small synaptic vesicles at the neuromuscular junction. Mol Neurobiol 2013; 48(1): 120-7.
[http://dx.doi.org/10.1007/s12035-013-8423-9] [PMID: 23471747]
[35]
Benecke R. Clinical relevance of botulinum toxin immunogenicity. BioDrugs 2012; 26(2): e1-9.
[http://dx.doi.org/10.2165/11599840-000000000-00000] [PMID: 22385408]
[36]
Hefter H, Hartmann C, Kahlen U, Moll M, Bigalke H. Prospective analysis of neutralising antibody titres in secondary non-responders under continuous treatment with a botulinumtoxin type A preparation free of complexing proteins – a single cohort 4-year follow-up study. BMJ 2012; e000646.
[37]
Lotta S, Scelsi R, Alfonsi E, et al. Morphometric and neurophysiological analysis of skeletal muscle in paraplegic patients with traumatic cord lesion. Paraplegia 1991; 29(4): 247-52.
[PMID: 1831255]
[38]
Ianieri G, Marvulli R, Gallo GA, Fiore P, Megna M. “Appropriate Treatment” and therapeutic window in spasticity treatment with Incobotulinumtoxin A: From 100 to 1000 units. Toxins (Basel) 2018; 10(4): 140.
[http://dx.doi.org/10.3390/toxins10040140] [PMID: 29597251]
[39]
Dressler D, Saberi FA, Kollewe K, Schrader C. Safety aspects of incobotulinumtoxin A high-dose therapy. J Neural Transm (Vienna) 2015; 122(2): 327-33.
[http://dx.doi.org/10.1007/s00702-014-1252-9] [PMID: 25030362]
[40]
Wissel J, Bensmail D, Ferreira JJ, et al. Safety and efficacy of incobotulinumtoxin A doses up to 800 U in limb spasticity: The TOWER study. Neurology 2017; 88(14): 1321-8.
[http://dx.doi.org/10.1212/WNL.0000000000003789] [PMID: 28283596]
[41]
Merz Pharma UK Ltd. XEOMIN® 100 U summary of product characteristics. Available from: org.uk/emc/medicine/20666
[42]
Merz Pharmaceuticals L. Xeomin® US Prescribing Information. Available from: xeomin.com/wp-content/uploads/xeomin-full-prescribing-information.pdf(Accessed January 6, 2016).
[43]
Fabbri M, Leodori G, Fernandes RM, et al. Neutralizing anti-body and botulinum toxin therapy: A systematic review and meta-analysis. Neurotox Res 2016; 29(1): 105-17.
[http://dx.doi.org/10.1007/s12640-015-9565-5] [PMID: 26467676]
[44]
Ianieri G, Saggini R, Marvulli R, et al. New approach in the assessment of the tone, elasticity and the muscular resistance: Nominal scales vs MYOTON. Int J Immunopathol Pharmacol 2009; 22(3) (Suppl.): 21-4.
[http://dx.doi.org/10.1177/03946320090220S304] [PMID: 19887038]
[45]
Marvulli R, Megna M, Romanelli E, et al. Effectiveness of the treatment with botulinum toxin type A (BTX-A) in the management of the spasticity in patients with amyotrophic lateral sclerosis (ALS). Clin Immunol Endocr Metab Drugs 2016; 3(1): 73-7.
[http://dx.doi.org/10.2174/2212707003666160810143854]
[46]
Marvulli R, Mastromauro L, Romanelli E, et al. How botulinum toxin type A- occupational therapy (OT)-functional electrical stimulation (FES) modify spasticity and functional recovery in patients with upper limb spasticity post stroke. Clin Immunol Endocr Metab Drugs 2016; 62-7.
[http://dx.doi.org/10.2174/2212707003666160728143344]
[47]
Munari D, Pedrinolla A, Smania N, et al. High-intensity treadmill training improves gait ability, VO2 peak and cost of walking in stroke survivors: Preliminary results of a pilot randomized controlled trial. Eur J Phys Rehabil Med 2016; 54(3): 408-18.
[PMID: 27575015]
[48]
Picelli A, Bacciga M, Melotti C, et al. Combined effects of robot assisted gait training and botulinum toxin type A on spastic equinus foot in patients with chronic stroke: A pilot, single blind, randomized controlled trial. Eur J Phys Rehabil Med 2016; 52(6): 759-66.
[PMID: 27098300]
[49]
Demetrios M, Khan F, Turner-Stokes L, Brand C, McSweeney S. Multidisciplinary rehabilitation following botulinum toxin and other focal intramuscular treatment for post-stroke spasticity. Cochrane Database Syst Rev 2013; 6(6): CD009689.
[http://dx.doi.org/10.1002/14651858.CD009689.pub2] [PMID: 23740539]
[50]
Picelli A, Tamburin S, Cavazza S, et al. Relationship between ultrasonographic, electromyographic, and clinical parameters in adult stroke patients with spastic equinus: An observational study. Arch Phys Med Rehabil 2014; 95(8): 1564-70.
[http://dx.doi.org/10.1016/j.apmr.2014.04.011] [PMID: 24792138]
[51]
Synnot A, Chau M, Pitt V, et al. Interventions for managing skeletal muscle spasticity following traumatic brain injury. Cochrane Database Syst Rev 2017; 11: CD008929.
[http://dx.doi.org/10.1002/14651858.CD008929.pub2] [PMID: 29165784]
[52]
Gao F, Grant TH, Roth EJ, Zhang LQ. Changes in passive mechanical properties of the gastrocnemius muscle at the muscle fascicle and joint levels in stroke survivors. Arch Phys Med Rehabil 2009; 90(5): 819-26.
[http://dx.doi.org/10.1016/j.apmr.2008.11.004] [PMID: 19406302]
[53]
Santamato A. Safety and efficacy of incobotulinumtoxinA as a potential treatment for poststroke spasticity. Neuropsychiatr Dis Treat 2016; 12: 251-63.
[http://dx.doi.org/10.2147/NDT.S86978] [PMID: 26869793]
[54]
Fortuna R, Vaz MA, Sawatsky A, Hart DA, Herzog W. A clinically relevant BTX-A injection protocol leads to persistent weakness, contractile material loss, and an altered mRNA expression phenotype in rabbit quadriceps muscles. J Biomech 2015; 48(10): 1700-6.
[http://dx.doi.org/10.1016/j.jbiomech.2015.05.018] [PMID: 26087882]
[55]
McCrory P, Turner-Stokes L, Baguley IJ, et al. Botulinum toxin A for treatment of upper limb spasticity following stroke: A multicentre randomized placebo-controlled study of the effects on quality of life and other person-centred outcomes. J Rehabil Med 2009; 41(7): 536-44.
[http://dx.doi.org/10.2340/16501977-0366] [PMID: 19543664]
[56]
Bensmail D, Hanschmann A, Wissel J. Satisfaction with botulinum toxin treatment in post-stroke spasticity: Results from two cross-sectional surveys (patients and physicians). J Med Econ 2014; 17(9): 618-25.
[http://dx.doi.org/10.3111/13696998.2014.925462] [PMID: 24841450]
[57]
Megna M, Marvulli R, Farì G, et al. Pain and muscles properties modifications after botulinum toxin type A (BTX-A) and radial extracorporeal shock wave (rESWT) combined treat-ment. Endocr Metab Immune Disord Drug Targets 2019; 19(8): 1127-33.
[http://dx.doi.org/10.2174/1871530319666190306101322] [PMID: 30843498]
[58]
Manganotti P, Amelio E. Long-term effect of shock wave therapy on upper limb hypertonia in patients affected by stroke. Stroke 2005; 36(9): 1967-71.
[http://dx.doi.org/10.1161/01.STR.0000177880.06663.5c] [PMID: 16109905]
[59]
Smania N, Picelli A, Munari D, et al. Rehabilitation procedures in the management of spasticity. Eur J Phys Rehabil Med 2010; 46(3): 423-38.
[PMID: 20927008]
[60]
Riccardo M, Angela L, Angela D, et al. Combined treatment Fkt-botulinum toxin type A (Btx-A) in patients with strumpell-lorrain disease. Curr Pharm Des 2016; 22(6): 758-63.
[http://dx.doi.org/10.2174/1381612822666151204001830] [PMID: 26648460]
[61]
Turcu-Stiolica A, Subtirelu MS, Bumbea AM. Can incobotulinumtoxin-A treatment improve quality of life better than conventional therapy in spastic muscle post-stroke patients? Results from a pilot study from a single center. Brain Sci 2021; 11(7): 934.
[http://dx.doi.org/10.3390/brainsci11070934] [PMID: 34356168]
[62]
Marciniak C, Munin MC, Brashear A, et al. IncobotulinumtoxinA efficacy and safety in adults with upper-limb spasticity following stroke: Results from the open-label extension period of a phase 3 study. Adv Ther 2019; 36(1): 187-99.
[http://dx.doi.org/10.1007/s12325-018-0833-7] [PMID: 30484117]
[63]
Levy J, Molteni F, Cannaviello G, Lansaman T, Roche N, Bensmail D. Does botulinum toxin treatment improve upper limb active function? Ann Phys Rehabil Med 2019; 62(4): 234-40.
[http://dx.doi.org/10.1016/j.rehab.2018.05.1320] [PMID: 29960017]