Factors influencing response to Botulinum toxin type A in patients with idiopathic cervical dystonia: results from an international observational study

Vijay P Misra, Edvard Ehler, Benjamin Zakine, Pascal Maisonobe, Marion Simonetta-Moreau, INTEREST IN CD group, Vijay P Misra, Edvard Ehler, Benjamin Zakine, Pascal Maisonobe, Marion Simonetta-Moreau, INTEREST IN CD group

Abstract

Objectives: Real-life data on response to Botulinum toxin A (BoNT-A) in cervical dystonia (CD) are sparse. An expert group of neurologists was convened with the overall aim of developing a definition of treatment response, which could be applied in a non-interventional study of BoNT-A-treated subjects with CD.

Design: International, multicentre, prospective, observational study of a single injection cycle of BoNT-A as part of normal clinical practice.

Setting: 38 centres across Australia, Belgium, Czech Republic, France, Germany, The Netherlands, Portugal, Russia and the UK.

Participants: 404 adult subjects with idiopathic CD. Most subjects were women, aged 41-60 years and had previously received BoNT-A.

Outcome measures: Patients were classified as responders if they met all the following four criteria: magnitude of effect (≥25% improvement Toronto Western Spasmodic Torticollis Rating Scale), duration of effect (≥12-week interval between the BoNT-A injection day and subject-reported waning of treatment effect), tolerability (absence of severe related adverse event) and subject's positive Clinical Global Improvement (CGI).

Results: High rates of response were observed for magnitude of effect (73.6%), tolerability (97.5%) and subject's clinical global improvement (69.8%). The subjective duration of effect criterion was achieved by 49.3% of subjects; 28.6% of subjects achieved the responder definition. Factors most strongly associated with response were age (<40 years; OR 3.9, p<0.05) and absence of baseline head tremor (OR 1.5; not significant).

Conclusions: Three of four criteria were met by most patients. The proposed multidimensional definition of response appears to be practical for routine practice. Unrealistically high patient expectation and subjectivity may influence the perception of a quick waning of effect, but highlights that this aspect may be a hurdle to response in some patients. CLINICAL REGISTRATION NUMBER: (NCT00833196; ClinicalTrials.gov).

Conflict of interest statement

Competing interests: VPM: Consultancies: Ad hoc consultant to Ipsen Pharma and Syntaxin Ltd. Advisory Boards: Attended Ipsen Pharma Medical Advisory Boards. Contracts: Contracts with Ipsen Pharma and Syntaxin Ltd related to ad hoc Consultancies/Advisory boards. EE: Grants: IGA Ministry of Health, Czech Republic. BZ and PM: Employment: Ipsen. MS-M: Consultancies: Ipsen. Employment: Hôpitaux de Toulouse and Paul Sabatier University.

Figures

Figure 1
Figure 1
Responder analysis. AEs, adverse events; CGI, Clinical Global Improvement; TWSTRS, Toronto Western Spasmodic Torticollis Rating Scale.
Figure 2
Figure 2
Subgroup analyses of responders (efficacy population). BoNT-A, Botulinum toxin A; CD, cervical dystonia; EMG, electromyography.
Figure 3
Figure 3
Occurrence of AEs with frequently used BoNT-A preparation. AEs, adverse events; BoNT-A, Botulinum toxin A.

References

    1. Bhidayasiri R, Tarsy D. Treatment of dystonia. Expert Rev Neurother 2006;6:863–86
    1. Nutt JG, Muenter MD, Aronson A, et al. Epidemiology of focal and generalized dystonia in Rochester, Minnesota. Mov Disord 1988;3:188–94
    1. Velickovic M, Benabou R, Brin MF. Cervical dystonia pathophysiology and treatment options. Drugs 2001;61:1921–43
    1. Jankovic J, Leder S, Warner D, et al. Cervical dystonia: clinical findings and associated movement disorders. Neurology 1991;41:1088–91
    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
    1. Costa J, Espirito-Santo C, Borges A, et al. Botulinum toxin type A therapy for cervical dystonia. Cochrane Database Syst Rev 2005(1):CD003633.
    1. Brashear A. Botulinum toxin type A in the treatment of patients with cervical dystonia. Biologics 2009;3:1–7
    1. Simpson DM, Blitzer A, Brashear A, et al. ; Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology 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;70:1699–706
    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;20:783–91
    1. Costa J, Espírito-Santo C, Borges A, et al. Botulinum toxin type B for cervical dystonia. Cochrane Database Syst Rev 2005(1):CD004315.
    1. Consky ES, Lang AE. Clinical assessments of patients with cervical dystonia. In: Jankovic J, Hallett M, eds. Therapy with Botulinum Toxin. New York: M. Dekker, 1994:211–37
    1. Tsui JK, Eisen A, Stoessl AJ, et al. Double-blind study of botulinum toxin in spasmodic torticollis. Lancet 1986;2:245–7
    1. Cano SJ, Hobart JC, Edwards M, et al. CDIP-58 can measure the impact of botulinum toxin treatment in cervical dystonia. Neurology 2006;67:2230–2
    1. Ranoux D, Gury C, Fondarai J, et al. Respective potencies of Botox and Dysport: a double blind, randomised, crossover study in cervical dystonia. J Neurol Neurosurg Psychiatry 2002;72:459–62
    1. Stacy M. Epidemiology, clinical presentation, and diagnosis of cervical dystonia. Neurol Clin 2008;26(Suppl 1):23–42
    1. Hefter H, Kupsch A, Müngersdorf M, et al. ; Dysport Cervical Dystonia Study Group A botulinum toxin A treatment algorithm for de novo management of torticollis and laterocollis. BMJ Open 2011;1:e000196
    1. Mohammadi B, Buhr N, Bigalke H, et al. A long-term follow-up of botulinum toxin A in cervical dystonia. Neurol Res 2009;31:463–6
    1. Vivancos-Matellano F, Ybot-Gorrin I, Diez-Tejedor E. A 17-year experience of abobotulinumtoxinA in cervical dystonia. Int J Neurosci. Published Online First: 20 March 2012. doi:
    1. Truong D, Comella C, Fernandez HH, et al. ; Dysport Benign Essential Blepharospasm Study Group Efficacy and safety of purified botulinum toxin type A (Dysport) for the treatment of benign essential blepharospasm: a randomized, placebo-controlled, phase II trial. Parkinsonism Relat Disord 2008;14:407–14
    1. Truong D, Brodsky M, Lew M, et al. ; Global Dysport Cervical Dystonia Study Group Long-term efficacy and safety of botulinum toxin type A (Dysport) in cervical dystonia. Parkinsonism Relat Disord 2010;16:316–23
    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. Skogseid IM, Malt UF, Roislien J, et al. Determinants and status of quality of life after long-term botulinum toxin therapy for cervical dystonia. Eur J Neurol 2007;14:1129–37

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