The pooled incidences of treatment-emergent adverse events (TEAEs) were examined by indication using the integrated clinical database of Merz-sponsored, placebo-controlled, or repeat-dose studies of incobotulinumtoxinA in adults with cervical dystonia, blepharospasm, limb spasticity, sialorrhea, or essential tremor of the upper limb. Overall incidences of TEAEs, serious TEAEs, TEAEs leading to discontinuation, fatal TEAEs, TEAEs of special interest (TEAESIs; indicating possible toxin spread), and treatment-related (TR) events were determined for incobotulinumtoxinA and placebo after a single injection and for repeated dose cycles of incobotulinumtoxinA. The most frequent events after a single dose of incobotulinumtoxinA are summarized. After a single cycle, incidences of overall TEAEs were similar between incobotulinumtoxinA and the placebo in most indications, although between-indication differences were observed. Few TEAEs led to incobotulinumtoxinA discontinuation; there were no fatal TEAEs with incobotulinumtoxinA. In general, repeated cycles did not increase the incidence of any event. The most frequent TR-TEAEs were indication-dependent, including dysphagia for indications affecting the head or neck. The TR-TEAESIs across all indications were most commonly muscular weakness, dysphagia and dry mouth. Overall, the results of this pooled analysis support and extend the favorable safety and tolerability profile of incobotulinumtoxinA for the treatment of adult neurological disorders established by individual clinical studies.

• Klíčová slova
• blepharospasm, cervical dystonia, essential tremor, immunogenicity, incobotulinumtoxinA, motor disorders, neurological disorders, safety, sialorrhea, spasticity,
• MeSH
• botulotoxiny typ A * škodlivé účinky   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• lidé MeSH
• nemoci nervového systému * farmakoterapie   MeSH
• nervosvalové látky * škodlivé účinky   MeSH
• poruchy polykání * farmakoterapie   MeSH
• tortikolis * farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• botulotoxiny typ A * MeSH
• incobotulinumtoxinA MeSH Prohlížeč
• nervosvalové látky * MeSH

BACKGROUND: For many indications, BoNT/A is repetitively injected with the risk of developing neutralizing antibodies (NABs). Therefore, it is important to analyze whether there is a difference in antigenicity between the different licensed BoNT/A preparations. METHODS: In this cross-sectional study, the prevalence of NABs was tested by means of the sensitive mouse hemidiaphragm assay (MHDA) in 645 patients. Patients were split into those having exclusively been treated with the complex protein-free incoBoNT/A preparation (CF-MON group) and those having started BoNT/A therapy with a complex protein-containing BoNT/A preparation (CC-I group). This CC-I group was split into those patients who remained either on abo- or onaBoNT/A (CC-MON group) and those who had been treated with at least two BoNT/A preparations (CC-SWI group). To balance treatment duration, only CC-MON patients who did not start their BoNT/A therapy more than 10 years before recruitment (CC-MON-10 group) were further analyzed. The log-rank test was used to compare the prevalence of NABs in the CF-MON and CC-MON-10 group. RESULTS: In the CF-MON subgroup, no patient developed NABs. In the CC-I group, 84 patients were NAB-positive. NABs were found in 33.3% of those who switched preparations (CC-SWI) and in 5.9% of the CC-MON-10 group. Kaplan-Meier curves for remaining NAB-negative under continuous BoNT/A therapy were significantly different (p < 0.035) between the CF-MON and CC-MON-10 group. CONCLUSION: Frequent injections of a complex protein-containing BoNT/A preparation are associated with significantly higher risks of developing NABs than injections with the same frequency using the complex protein-free incoBoNT/A preparation.

• Klíčová slova
• Botulinum toxin type A preparations, Complex proteins, Difference in antigenicity, IncobotulinumtoxinA, Neutralizing antibodies,
• MeSH
• botulotoxiny typ A * MeSH
• myši MeSH
• nervosvalové látky * MeSH
• neutralizující protilátky MeSH
• průřezové studie MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• botulotoxiny typ A * MeSH
• nervosvalové látky * MeSH
• neutralizující protilátky MeSH

Botulinum toxin (BT) therapy is a complex and highly individualised therapy defined by treatment algorithms and injection schemes describing its target muscles and their dosing. Various consensus guidelines have tried to standardise and to improve BT therapy. We wanted to update and improve consensus guidelines by: (1) Acknowledging recent advances of treatment algorithms. (2) Basing dosing tables on statistical analyses of real-life treatment data of 1831 BT injections in 36 different target muscles in 420 dystonia patients and 1593 BT injections in 31 different target muscles in 240 spasticity patients. (3) Providing more detailed dosing data including typical doses, dose variabilities, and dosing limits. (4) Including total doses and target muscle selections for typical clinical entities thus adapting dosing to different aetiologies and pathophysiologies. (5) In addition, providing a brief and concise review of the clinical entity treated together with general principles of its BT therapy. For this, we collaborated with IAB-Interdisciplinary Working Group for Movement Disorders which invited an international panel of experts for the support.

• Klíčová slova
• Botulinum toxin, Consensus guidelines, Dose limits, Dose variability, Dosing tables, Dystonia, Spasticity, Target muscles, Therapy, Total dose, Treatment algorithms, Typical dose,
• MeSH
• algoritmy MeSH
• botulotoxiny typ A * MeSH
• botulotoxiny * MeSH
• dystonické poruchy * farmakoterapie   MeSH
• dystonie * farmakoterapie   MeSH
• lidé MeSH
• svalová spasticita farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• botulotoxiny typ A * MeSH
• botulotoxiny * MeSH

OBJECTIVE: This post hoc analysis assessed the impact of repeated incobotulinumtoxinA injections on muscle tone, disability, and caregiver burden in adults with upper-limb post-stroke spasticity. DESIGN: Data from the double-blind, placebo-controlled main period and three open-label extension cycles of two Phase 3, randomized, multicentre trials were pooled. METHODS: Subjects received incobotulinumtoxinA 400 Units at 12-week intervals (±3 days) (study 3001, NCT01392300) or ≤ 400 Units at ≥12-week intervals based on clinical need (study 0410, NCT00432666). Ashworth Scale (AS) arm sumscore (sum of elbow, wrist, finger and thumb flexor, and forearm pronator AS scores), Disability Assessment Scale (DAS), and Carer Burden Scale (CBS) scores were assessed. RESULTS: Among 465 subjects, from study baseline to 4 weeks post-injection, mean (standard deviation) AS arm sumscore improved continuously: main period, -3.23 (2.55) (placebo, -1.49 (2.09)); extension cycles 1, 2, and 3, -4.38 (2.85), -4.87 (3.05), and -5.03 (3.02), respectively. DAS principal target domain responder rate increased from 47.4% in the main period (placebo 27.2%) to 66.6% in extension cycle 3. Significant improvements in CBS scores 4 weeks post-injection accompanied improved functional disability in all cycles. CONCLUSION: IncobotulinumtoxinA conferred sustained improvements in muscle tone, disability, and caregiver burden in subjects with upper-limb post-stroke spasticity.

• Klíčová slova
• botulinum neurotoxin, caregiver burden, duration of effect, incobotulinumtoxinA, rehabilitation, spasticity, upper limb,
• MeSH
• botulotoxiny typ A farmakologie   terapeutické užití   MeSH
• cévní mozková příhoda komplikace   farmakoterapie   MeSH
• dvojitá slepá metoda MeSH
• horní končetina patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nervosvalové látky farmakologie   terapeutické užití   MeSH
• svalová spasticita farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• botulotoxiny typ A MeSH
• incobotulinumtoxinA MeSH Prohlížeč
• nervosvalové látky MeSH

The efficacy and safety of incobotulinumtoxinA ≤400 U was demonstrated in subjects with post-stroke upper-limb spasticity in a randomized, double-blind Phase 3 study with an open-label extension (OLEX; EudraCT number 2005-003951-11, NCT00432666). We report a post-hoc analysis of the duration of the treatment effect. Subjects completing the placebo-controlled main period (single injection cycle with 12-20-week observation) entered the OLEX and received a maximum of five further treatments (maximum duration 69 weeks) with incobotulinumtoxinA ≤400 U at flexible intervals with a minimum duration of 12 weeks, based on clinical need. Intervals between two consecutive incobotulinumtoxinA injections, excluding treatment intervals prior to the end-of-study visit, were evaluated. Of 437 incobotulinumtoxinA treatment intervals, 415 received by 136 subjects were included in the post-hoc analysis. More than half (52.3%; 217/415) of all incobotulinumtoxinA reinjections were administered at Week ≥14, 31.1% (129/415) at Week ≥16, 19.0% (79/415) at Week ≥18, and 11.6% (48/415) at Week ≥20. The duration of effect may vary and can exceed 20 weeks or more, which was observed in at least one injection cycle in 29.4% (40/136) subjects over the course of their treatment. Data show that incobotulinumtoxinA retreatment for upper-limb spasticity may not be required at 12-week intervals and provides evidence for flexible treatment intervals beyond this time frame.

• Klíčová slova
• duration of effect, incobotulinumtoxinA, post-stroke, treatment interval, upper-limb spasticity,
• Publikační typ
• časopisecké články MeSH

Spasticity is a symptom occurring in many neurological conditions including stroke, multiple sclerosis, hypoxic brain damage, traumatic brain injury, tumours and heredodegenerative diseases. It affects large numbers of patients and may cause major disability. So far, spasticity has merely been described as part of the upper motor neurone syndrome or defined in a narrowed neurophysiological sense. This consensus organised by IAB-Interdisciplinary Working Group Movement Disorders wants to provide a brief and practical new definition of spasticity-for the first time-based on its various forms of muscle hyperactivity as described in the current movement disorders terminology. We propose the following new definition system: Spasticity describes involuntary muscle hyperactivity in the presence of central paresis. The involuntary muscle hyperactivity can consist of various forms of muscle hyperactivity: spasticity sensu strictu describes involuntary muscle hyperactivity triggered by rapid passive joint movements, rigidity involuntary muscle hyperactivity triggered by slow passive joint movements, dystonia spontaneous involuntary muscle hyperactivity and spasms complex involuntary movements usually triggered by sensory or acoustic stimuli. Spasticity can be described by a documentation system grouped along clinical picture (axis 1), aetiology (axis 2), localisation (axis 3) and additional central nervous system deficits (axis 4). Our new definition allows distinction of spasticity components accessible to BT therapy and those inaccessible. The documentation sheet presented provides essential information for planning of BT therapy.

• Klíčová slova
• Botulinum toxin therapy, Contractures, Dystonia, Rigidity, Spasms, Spasticity, Treatment,
• MeSH
• botulotoxiny terapeutické užití   MeSH
• lidé MeSH
• neurotoxiny terapeutické užití   MeSH
• pohybové poruchy farmakoterapie   MeSH
• svalová spasticita diagnóza   farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• botulotoxiny MeSH
• neurotoxiny MeSH