Botulinum toxin therapy for cervical dystonia: the science of dosing

Virgilio Gerald H Evidente, Eric J Pappert, Virgilio Gerald H Evidente, Eric J Pappert

Abstract

The first-line treatment for cervical dystonia (CD) is botulinum toxin type A (BoNT-A), which has been established as a highly effective and well-tolerated therapy. However, this treatment is also complex and challenging to apply in clinical practice. Approximately 20% of patients discontinue therapy due to treatment failure, adverse effects, and other reasons. In addition, expert consensus recommendations are lacking to guide physicians in the optimal use of BoNT-A for CD. Among the issues still to be clarified is the optimal dosing frequency. The generally accepted standard for intervals between BoNT-A injections is ≥12 weeks; however, this standard is based primarily on the methodology of pivotal trials for the BoNT-A products, rather than on evidence that it is optimal in comparison to other intervals. While some retrospective, observational studies of BoNT-A used in clinical practice appear to support the use of ≥12-week dosing intervals, it is often unclear in these studies how the need for reinjection was determined. In contrast, a prospective dose-ranging trial in which patients were allowed to request reinjection as early as 8 weeks showed that about half of patients receiving abobotulinumtoxinA, at the currently recommended initial dose of 500 U, requested reinjection at 8 weeks. Moreover, results from an open-label, 68-week extension phase of the pivotal trial of incobotulinumtoxinA showed that 47.1% of patients had received reinjection at ≤12 weeks. Ongoing studies, such as the Cervical Dystonia Patient Registry for Observation of BOTOX® Efficacy (CD PROBE), may help clarify this question of optimal dosing intervals for BoNT-A in CD.

Keywords: AbobotulinumtoxinA; cervical dystonia; incobotulinumtoxinA; onabotulinumtoxinA; rimabotulinumtoxinB.

Conflict of interest statement

Conflict of Interests: V.G.H.E. has received consulting compensation and research support from Merz North America, Inc. E.J.P. was an employee of Merz North America, Inc.

Figures

Figure 1. Mean (SD) Toronto Western Spasmodic…
Figure 1. Mean (SD) Toronto Western Spasmodic Torticollis Rating Scale Total Score.
Results at 4 weeks after each of five injection sessions. Error bars represent SD. *p

References

    1. Chan J, Brin MF, Fahn S. Idiopathic cervical dystonia: Clinical characteristics. Mov Disord. 1991;6:119–126. doi: 10.1002/mds.870060206.
    1. Jankovic J, Leder S, Warner D, Schwartz K. Cervical dystonia: Clinical findings and associated movement disorders. Neurology. 1991;41:1088–1091. doi: 10.1212/WNL.41.7.1088.
    1. Brashear A. Botulinum toxin type A in the treatment of patients with cervical dystonia. Biologics. 2009;3:1–7.
    1. Epidemiological Study of Dystonia in Europe (ESDE) Collaborative Group A prevalence study of primary dystonia in eight European countries. J Neurol. 2000;247:787–792. doi: 10.1007/s004150070094.
    1. Jankovic J, Tsui J, Bergeron C. Prevalence of cervical dystonia and spasmodic torticollis in the United States general population. Parkinsonism Relat Disord. 2007;13:411–416. doi: 10.1016/j.parkreldis.2007.02.005.
    1. Camfield L, Ben-Shlomo Y, Warner TT. Impact of cervical dystonia on quality of life. Mov Disord. 2002;17:838–841. doi: 10.1002/mds.10127.
    1. Slawek J, Friedman A, Potulska A, et al. Factors affecting the health-related quality of life of patients with cervical dystonia and the impact of botulinum toxin type A injections. Funct Neurol. 2007;22:95–100.
    1. Muller J, Kemmler G, Wissel J, et al. The impact of blepharospasm and cervical dystonia on health-related quality of life and depression. J Neurol. 2002;249:842–846. doi: 10.1007/s00415-002-0773-6.
    1. Ben-Shlomo Y, Camfield L, Warner T. What are the determinants of quality of life in people with cervical dystonia? J Neurol Neurosurg Psychiatry. 2002;72:608–614. doi: 10.1136/jnnp.72.5.608.
    1. Tarsy D, Simon DK. Dystonia. N Engl J Med. 2006;355:818–829. doi: 10.1056/NEJMra055549.
    1. Neychev VK, Fan X, Mitev VI, Hess EJ, Jinnah HA. The basal ganglia and cerebellum interact in the expression of dystonic movement. Brain. 2008;131:2499–2509. doi: 10.1093/brain/awn168.
    1. Zoons E, Booij J, Nederveen AJ, Dijk JM, Tijssen MA. Structural, functional and molecular imaging of the brain in primary focal dystonia–a review. Neuroimage. 2011;56:1011–1020. doi: 10.1016/j.neuroimage.2011.02.045.
    1. Vidailhet M, Grabli D, Roze E. Pathophysiology of dystonia. Curr Opin Neurol. 2009;22:406–413. doi: 10.1097/WCO.0b013e32832d9ef3.
    1. 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;70:1699–1706. doi: 10.1212/01.wnl.0000311389.26145.95.
    1. Albanese A, Asmus F, Bhatia KP, et al. EFNS guidelines on diagnosis and treatment of primary dystonias. Eur J Neurol. 2011;18:5–18. doi: 10.1111/j.1468-1331.2010.03042.x.
    1. Swope D, Barbano R. Treatment recommendations and practical applications of botulinum toxin treatment of cervical dystonia. Neurol Clin. 2008;26(Suppl 1):54–65. doi: 10.1016/S0733-8619(08)80005-9.
    1. Jankovic J. Botulinum toxin in clinical practice. J Neurol Neurosurg Psychiatry. 2004;75:951–957. doi: 10.1136/jnnp.2003.034702.
    1. Poewe W, Deuschl G, Nebe A, et al. What is the optimal dose of botulinum toxin A in the treatment of cervical dystonia? Results of a double blind, placebo controlled, dose ranging study using Dysport. German Dystonia Study Group. J Neurol Neurosurg Psychiatry. 1998;64:13–17. doi: 10.1136/jnnp.64.1.13.
    1. Hefter H, Kupsch A, Mungersdorf M, et al. A botulinum toxin A treatment algorithm for de novo management of torticollis and laterocollis. BMJ Open. 2011;1:e000196. doi: 10.1136/bmjopen-2011-000196.
    1. Benecke R, Dressler D. Botulinum toxin treatment of axial and cervical dystonia. Disabil Rehabil. 2007;29:1769–1777. doi: 10.1080/01421590701568262.
    1. Jankovic J, Adler CH, Charles PD, et al. Rationale and design of a prospective study: Cervical Dystonia Patient Registry for Observation of OnaBotulinumtoxinA Efficacy (CD PROBE) BMC Neurol. 2011;11:140. doi: 10.1186/1471-2377-11-140.
    1. Comella CL, Thompson PD. Treatment of cervical dystonia with botulinum toxins. Eur J Neurol. 2006;13(Suppl 1):16–20. doi: 10.1111/j.1468-1331.2006.01440.x.
    1. Cano SJ, Hobart JC, Fitzpatrick R, Bhatia K, Thompson AJ, Warner TT. Patient-based outcomes of cervical dystonia: A review of rating scales. Mov Disord. 2004;19:1054–1059. doi: 10.1002/mds.20055.
    1. Zoons E, Dijkgraaf MG, Dijk JM, van Schaik IN, Tijssen MA. Botulinum toxin as treatment for focal dystonia: A systematic review of the pharmaco-therapeutic and pharmaco-economic value. J Neurol. 2012;259(12):2519–26. doi: 10.1007/s00415-012-6510-x. Dec.
    1. Dressler D. Clinical presentation and management of antibody-induced failure of botulinum toxin therapy. Mov Disord. 2004;19(Suppl 8):S92–100. doi: 10.1002/mds.20022.
    1. Kessler KR, Skutta M, Benecke R. Long-term treatment of cervical dystonia with botulinum toxin A: Efficacy, safety, and antibody frequency. German Dystonia Study Group. J Neurol. 1999;246:265–274. doi: 10.1007/s004150050345.
    1. Brashear A, Bergan K, Wojcieszek J, Siemers ER, Ambrosius W. Patients' perception of stopping or continuing treatment of cervical dystonia with botulinum toxin type A. Mov Disord. 2000;15:150–153. doi: 10.1002/1531-8257(200001)15:1<150::AID-MDS1024>;2-X.
    1. Hsiung GY, Das SK, Ranawaya R, Lafontaine AL, Suchowersky O. Long-term efficacy of botulinum toxin A in treatment of various movement disorders over a 10-year period. Mov Disord. 2002;17:1288–1293. doi: 10.1002/mds.10252.
    1. Haussermann P, Marczoch S, Klinger C, Landgrebe M, Conrad B, Ceballos-Baumann A. Long-term follow-up of cervical dystonia patients treated with botulinum toxin A. Mov Disord. 2004;19:303–308. doi: 10.1002/mds.10659.
    1. Wissel J, Kanovsky P, Ruzicka E, et al. Efficacy and safety of a standardised 500 unit dose of Dysport (clostridium botulinum toxin type A haemaglutinin complex) in a heterogeneous cervical dystonia population: Results of a prospective, multicentre, randomised, double-blind, placebo-controlled, parallel group study. J Neurol. 2001;248:1073–1078. doi: 10.1007/s004150170028.
    1. Gelb DJ, Yoshimura DM, Olney RK, Lowenstein DH, Aminoff MJ. Change in pattern of muscle activity following botulinum toxin injections for torticollis. Ann Neurol. 1991;29:370–376. doi: 10.1002/ana.410290407.
    1. Lange O, Bigalke H, Dengler R, Wegner F, deGroot M, Wohlfarth K. Neutralizing antibodies and secondary therapy failure after treatment with botulinum toxin type A: Much ado about nothing? Clin Neuropharmacol. 2009;32:213–218. doi: 10.1097/WNF.0b013e3181914d0a.
    1. Costa J, Espirito-Santo C, Borges A, et al. Botulinum toxin type A therapy for cervical dystonia. Cochrane Database Syst Rev. 2005:CD003633.
    1. Costa J, Espirito-Santo C, Borges A, et al. Botulinum toxin type B for cervical dystonia. Cochrane Database Syst Rev. 2005:CD004315.
    1. Merz Pharmaceuticals, LLC XEOMIN® (incobotulinumtoxinA) for injection US Prescribing Information. 2011. Version 07/2011.
    1. Mejia NI, Vuong KD, Jankovic J. Long-term botulinum toxin efficacy, safety, and immunogenicity. Mov Disord. 2005;20:592–597. doi: 10.1002/mds.20376.
    1. Jankovic J, Vuong KD, Ahsan J. Comparison of efficacy and immunogenicity of original versus current botulinum toxin in cervical dystonia. Neurology. 2003;60:1186–1188. doi: 10.1212/.
    1. Brin MF, Comella CL, Jankovic J, Lai F, Naumann M. Long-term treatment with botulinum toxin type A in cervical dystonia has low immunogenicity by mouse protection assay. Mov Disord. 2008;23:1353–1360. doi: 10.1002/mds.22157.
    1. Naumann M, Carruthers A, Carruthers J, et al. Meta-analysis of neutralizing antibody conversion with onabotulinumtoxinA (BOTOX(R)) across multiple indications. Mov Disord. 2010;25(13):2211–8. doi: 10.1002/mds.23254. Oct 15.
    1. Ipsen Biopharm, Ltd Dysport® (abobotulinumtoxinA) for injection Prescribing Information. 2010. Version 04/2010.
    1. Benecke R. Xeomin in the treatment of cervical dystonia. Eur J Neurol. 2009;16(Suppl 2):6–10. doi: 10.1111/j.1468-1331.2009.02878.x.
    1. Frevert J. Xeomin is free from complexing proteins. Toxicon. 2009;54:697–701.
    1. Goschel H, Wohlfarth K, Frevert J, et al. Botulinum A toxin therapy: Neutralizing and nonneutralizing antibodies-therapeutic consequences. Exp Neurol. 1997;147:96–102. doi: 10.1006/exnr.1997.6580.
    1. Joshi SG, Elias M, Singh A, et al. Modulation of botulinum toxin-induced changes in neuromuscular function with antibodies directed against recombinant polypeptides or fragments. Neuroscience. 2011;179:208–222. doi: 10.1016/j.neuroscience.2011.01.033.
    1. Chinnapongse RB, Lew MF, Ferreira JJ, et al. Immunogenicity and long-term efficacy of botulinum toxin type B in the treatment of cervical dystonia: Report of 4 prospective, multicenter trials. Clin Neuropharmacol. 2012;35:215–223. doi: 10.1097/WNF.0b013e318263163c.
    1. Greene P, Fahn S, Diamond B. Development of resistance to botulinum toxin type A in patients with torticollis. Mov Disord. 1994;9:213–217. doi: 10.1002/mds.870090216.
    1. Jankovic J, Schwartz K. Response and immunoresistance to botulinum toxin injections. Neurology. 1995;45:1743–1746. doi: 10.1212/WNL.45.9.1743.
    1. Dressler D. Clinical features of antibody-induced complete secondary failure of botulinum toxin therapy. Eur Neurol. 2002;48:26–29. doi: 10.1159/000064953.
    1. Comella CL, Jankovic J, Brin MF. Use of botulinum toxin type A in the treatment of cervical dystonia. Neurology. 2000;55:S15–21.
    1. Jankovic J. Botulinum toxin therapy for cervical dystonia. Neurotox Res. 2006;9:145–148. doi: 10.1007/BF03033933.
    1. Allergan, Inc Botox® (onabotulinumtoxinA) for injection, for intramuscular, intradetruser, or intradermal use US Prescribing Information. 2011. Version 08/2011.
    1. Charles D, Brashear A, Hauser RA, et al. Efficacy, tolerability, and immunogenicity of onabotulinumtoxina in a randomized, double-blind, placebo-controlled trial for cervical dystonia. Clin Neuropharmacol. 2012;35:208–214. doi: 10.1097/WNF.0b013e31826538c7.
    1. Truong D, Duane DD, Jankovic J, et al. Efficacy and safety of botulinum type A toxin (Dysport) in cervical dystonia: Results of the first US randomized, double-blind, placebo-controlled study. Mov Disord. 2005;20:783–791. doi: 10.1002/mds.20403.
    1. Truong D, Brodsky M, Lew M, et al. Long-term efficacy and safety of botulinum toxin type A (Dysport) in cervical dystonia. Parkinsonism Relat Disord. 2010;14:331–335.
    1. Comella CL, Jankovic J, Truong DD, Hanschmann A, Grafe S. Efficacy and safety of incobotulinumtoxinA (NT 201, XEOMIN(R), botulinum neurotoxin type A, without accessory proteins) in patients with cervical dystonia. J Neurol Sci. 2011;308:103–109. doi: 10.1016/j.jns.2011.05.041.
    1. Fargel M, Psaila E. Results of a multi-national patient and physician survey on treatment satisfaction with current botulinum toxin treatment in focal dystonia (Abstract #980) Mov Disord. 2010;25:S511. doi: 10.1002/mds.22923.
    1. Sethi KD, Rodriguez R, Olayinka B. Satisfaction with botulinum toxin treatment: A cross-sectional survey of patients with cervical dystonia. J Med Econ. 2012;15:419–423. doi: 10.3111/13696998.2011.653726.
    1. Brashear A, Watts MW, Marchetti A, Magar R, Lau H, Wang L. Duration of effect of botulinum toxin type A in adult patients with cervical dystonia: A retrospective chart review. Clin Ther. 2000;22:1516–1524. doi: 10.1016/S0149-2918(00)83049-0.
    1. Evidente VG, Fernandez HH, LeDoux MS, et al. A randomized, double-blind study of repeated incobotulinumtoxinA (Xeomin(®)) in cervical dystonia. J Neural Transm. 2013;120:1699–1707. doi: 10.1007/s00702-013-1048-3.
    1. Evidente VG, Truong D, Jankovic J, et al. IncobotulinumtoxinA (Xeomin®) injected for blepharospasm or cervical dystonia according to patient needs is well tolerated. J Neurol Sci. 2014 doi: 10.1016/j.jns.2014.08.004. Aug 10. pii: S0022-510X(14)00517-6.
    1. Jankovic J, Adler CH, Charles PD, et al. Cervical dystonia patient registry for observation of Botox efficacy (CD PROBE): Interim results of physician-reported outcomes. Poster presented at 63rd Annual Meeting of the American Academy of Neurology. Accessed October 9, 2012 2011 April 9–16 (Honolulu, HI) .

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