Evaluation of the safety and efficacy of the Russian botulinum toxin-A relatox versus botox in treating arm and hand spasticity after ischemic stroke: A multicenter randomized trial

Objective: to evaluate the safety and efficacy of the first Russian botulinum toxin-A relatox versus botox in treating arm and hand spasticity after ischemic stroke.

Patients and methods. A multicenter randomized clinical trial was conducted in 6 centers of the Russian Federation, which covered 160 patients with prior ischemic stroke and upper limb spasticity (an Ashworth scale score of at least 2). Not earlier than 3 months after stroke, a single injection of relatox or botox was made, followed by the evaluation of changes in muscle tone and the presence and severity of adverse events (local and systemic reactions).

Results. After relatox injection, all the patients had significantly decreased upper limb muscle tone according to the Ashworth scale (p<0.05), which was recorded at all visits as compared to that at the baseline visit. The greatest muscle tone reduction was observed at 1 and 2 months after injection, and that in the pattern of fingers was seen at 3 months. The effect persisted within 3 months following the injection, which was confirmed by the Ashworth scale scores during the last visit as compared to the baseline one (p<0.05). No significant differences were found in muscle tone reductions between the relatox and botox groups (p>0.05). Relatox showed the good tolerability and safety that was comparable to those of the comparison drug. The number of registered local and systemic reactions was low and was not significantly different in both groups (p>0.05). There were no considerable differences in laboratory parameters and electrocardiographic findings in both patient groups (p>0.05). Serious adverse events were not detected during the study either.

Conclusion. The findings suggest that relatox is safe and efficient in decreasing upper limb muscle tone in patients after ischemic stroke, which is an important component in the structure of rehabilitation (first of all, functional recovery) of patients with spastic paresis of the upper limb.

1. Стаховская ЛВ, Клочихина ОА, Богатырева МД, Коваленко ВВ. Эпидемиология инсульта в России по результатам территориально-популяционного регистра (2009— 2010). Журнал неврологии и психиатрии им. С.С. Корсакова. 2013;113(5):4-10. [Stakhovskaya LV, Klochikhina OA, Bogatyreva MD, Kovalenko VV. Epidemiology of stroke in Russia according to the results of the territorial-population registry (2009–2010). Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2013;113(5):4-10. (InRuss.)].

2. Скворцова ВИ, Стаховская ЛВ, Айриян НЮ. Эпидемиология инсульта в Российской Федерации. ConsiliumMedicum. 2005;(1):10-2. [Skvortsova VI, Stakhovskaya LV, Airiyan NYu. Epidemiology of stroke in the Russian Federation. Consilium Medicum. 2005;(1):10-2. (In Russ.)].

3. Lance JW. Symposium synopsis. In: Feldman R, Young R, Koella W, editors. Disordered motor control. Chicago: Year Book Medical Publishers; 1980. P. 485–94.

4. Gracies JM. Pathophysiology of spastic paresis. II: Emergence of muscle overactivity. Muscle Nerve. 2005 May;31(5):552-71.

5. Mayer NH. Clinicophysiologic concepts of spasticity and motor dysfunction in adults with an upper motoneuron lesion. Muscle Nerve Suppl. 1997;6:S1-13.

6. Lundstrom E, Smits A, Borg J, Terent A. Four-fold increase in direct costs of stroke survivors with spasticity compared with stroke survivors without spasticity: the first year after the event. Stroke. 2010 Feb;41(2):319-24. doi: 10.1161/STROKEAHA.109.558619. Epub 2009 Dec 31.

7. Lundstrom E, Smits A, Terent A, Borg J. Time-course and determinants of spasticity during the first six months following first-ever stroke. J Rehabil Med. 2010 Apr;42(4):296- 301. doi: 10.2340/16501977-0509.

8. Lundstrom E, Terent A, Borg J. Prevalence of disabling spasticity 1 year after first-ever stroke. Eur J Neurol. 2008 Jun;15(6):533-9. doi: 10.1111/j.1468-1331.2008.02114.x. Epub 2008 Mar 18.

9. Sheean G. The neurophysiology of spasticity. In: Barnes MP, Johnson GR, Editors. Upper Motor Neurone Syndrome and Spasticity. New York: Cambridge University Press; 2008. P. 9–63.

10. Shaw LC, Price CI, van Wijck FM, et al. Botulinum Toxin for the Upper Limb after Stroke (BoTULS) Trial: effect on impairment, activity limitation, and pain. Stroke. 2011 May; 42(5):1371-9. doi: 10.1161/STROKEAHA.110.582197. Epub 2011 Mar 17.

11. Royal College of Physicians, British Society of Rehabilitation Medicine, Chartered Society of Physiotherapy, Neurology A.o.C.P.I.i. Spasticity in adults: management using botulinum toxin. National guidelines. London: RCP; 2009.

12. Хатькова СЕ, Орлова ОР, Тимербаева СЛ, Познякова ЕВ. Оценка клинического профиля пациентов со спастичностью верхней конечности, которым показаны инъекции ботулинического токсина типа А (по данным международного исследования). Журнал неврологии и психиатрии им. С.С. Корсакова. 2011;111(8):23- 6. [Khat'kova SE, Orlova OR, Timerbaeva SL, Poznyakova EV. Assessment of the clinical profile of patients with spasticity of the upper limb, which shows the injection of botulinum toxin type A (according to international survey). Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2011;111(8):23-6. (In Russ.)].

13. Gracies JM, Brashear A, Jech R, et al. Safety and efficacy of abobotulinumtoxinA for hemiparesis in adults with upper limb spasticity after stroke or traumatic brain injury: a doubleblind randomised controlled trial. Lancet Neurol. 2015 Oct;14(10):992-1001. doi: 10.1016/S1474-4422(15)00216-1. Epub 2015 Aug 26.

14. Bensmail D, Robertson JV, Fermanian C, Roby-Brami A. Botulinum toxin to treat upperlimb spasticity in hemiparetic patients: analysis of function and kinematics of reaching movements. Neurorehabil Neural Repair. 2010 Mar-Apr;24(3):273-81. doi: 10.1177/1545968309347682. Epub 2010 Jan 12.

15. Brashear A. Spasticity: diagnosis and management. 2nd ed. New York: Demos Medical Publishing; 2016.

16. Winstein CJ, Stein J, Arena R, et al Guidelines for Adult Stroke Rehabilitation and Recovery: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2016 Jun;47(6):e98-e169. doi: 10.1161/STR.0000000000000098. Epub 2016 May 4.

17. 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 Jan;41(1):13-25. doi: 10.2340/16501977-0303.

18. Simpson DM, Hallett M, Ashman EJ, 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 May 10;86(19):1818-26. doi: 10.1212/WNL.0000000000002560. Epub 2016 Apr 18.

19. Куликов АЮ, Угрехелидзе ДТ. Фармакоэкономическое исследование применения препаратов ботулинического токсина при терапии постинсультной спастичности верхней конечности. Фармакоэкономика: Теория и практика. 2014;2(3):28-37. [Kulikov AYu, Ugrekhelidze DT. Pharmacoeconomic study of the use of botulinum toxin in the treatment of post-stroke spasticity of the upper limb. Farmakoekonomika: Teoriya i praktika. 2014;2(3):28-37. (In Russ.)].

20. Орлова ОР, Тимербаева СЛ, Хатькова СЕ и др. Ботулинотерапия в клинической практике. В кн.: Голубев ВЛ, редактор. Избранные лекции по неврологии. Том 2. Москва: МЕДпресс-информ; 2012. С. 81-103. [Orlova OR, Timerbaeva SL, Khat'kova SE, et al. Botulinum toxin therapy in clinical practice. In: Golubev VL, editor. Izbrannye lektsii po nevrologii. Tom 2 [Selected lectures in neurology. Vol.2]. Moscow: MEDpress-inform; 2012. P. 81-103.]

21. Хатькова СЕ, Конева ЕС, Сидякина ИВ. Комплексная реабилитация больных с постинсультной спастичностью руки. Практическое руководство для врачей. Москва: ФГБУ «Лечебно-реабилитационный центр» Минздравсоцразвития России; 2011. [Khat'kova SE, Koneva ES, Sidyakina IV. Kompleksnaya reabilitatsiya bol'nykh s postinsul'tnoi spastichnost'yu ruki . Prakticheskoe rukovodstvo dlya vrachei [Comprehensive rehabilitation of patients with post-stroke spasticity of the hand. A practical guide for physicians]. Moscow: FGBU «Lechebno-reabilitatsionnyi tsentr» Minzdravsotsrazvitiya Rossii; 2011.]

22. Хатькова СЕ, Орлова ОР, Боцина АЮ и др. Основные принципы ведения пациентов с нарушением тонуса после очагового повреждения головного мозга. Consilium Medicum. 2016;18(2.1):25–33. [Khat'kova SE, Orlova OR, Botsina AYu, et al. The basic principles of managing the patients with impaired tone after focal brain damage. Consilium Medicum. 2016;18(2.1):25–33. (In Russ.)].

23. Райцева СС. Особенности проведения эстетической ботулинотерапии препаратом Релатокс®. Клинический опыт. Метаморфозы. 2017; (17):74-91. [Raitseva SS. The features of the aesthetic botulinum toxin therapy with Relatox®. Clinical experience. Metamorfozy. 2017; (17):74-91. (In Russ.)].