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Botulinum toxin therapy for cervical dystonia: the science of dosing.

Evidente VG, Pappert EJ - Tremor Other Hyperkinet Mov (N Y) (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Movement Disorders Center of Arizona, Scottsdale, AZ, USA.

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.

No MeSH data available.


Related in: MedlinePlus

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<0.001; p-value is a one-sample t-test of change in TWSTRS total score from the injection visit to the visit 4 weeks later (with no replacement of missing data).
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f01: 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<0.001; p-value is a one-sample t-test of change in TWSTRS total score from the injection visit to the visit 4 weeks later (with no replacement of missing data).

Mentions: During the extension phase, 191 (89%) patients received two or more injections.59 One-third of patients participating in the extension phase received re-injections at >14 weeks; the rest of the patients were roughly equally divided between the intervals of ≤10 weeks (22.5%), >10 to ≤12 weeks (24.6%); and >12 weeks to ≤14 weeks (19.4%).59 Notably, this showed that 47.1% of patients had received reinjections at median intervals of ≤12 weeks, which is shorter than the standard recommended interval for BoNT-A therapy for CD patients. Mean doses received for both dose groups (120 U and 240 U) were similar across all injection sections and interval groups.59 The mean changes from baseline in TWSTRS total scores in each interval group showed statistically significant improvements 4 weeks after each injection (p<0.0001) (Figure 1).59 In addition, there were no statistically significant differences in the overall occurrence of AEs between interval groups (Table 3).59 Increased antibody production occurred in three (1.3%) patients and had no correlation with dosing frequency during the extension phase.


Botulinum toxin therapy for cervical dystonia: the science of dosing.

Evidente VG, Pappert EJ - Tremor Other Hyperkinet Mov (N Y) (2014)

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<0.001; p-value is a one-sample t-test of change in TWSTRS total score from the injection visit to the visit 4 weeks later (with no replacement of missing data).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4233211&req=5

f01: 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<0.001; p-value is a one-sample t-test of change in TWSTRS total score from the injection visit to the visit 4 weeks later (with no replacement of missing data).
Mentions: During the extension phase, 191 (89%) patients received two or more injections.59 One-third of patients participating in the extension phase received re-injections at >14 weeks; the rest of the patients were roughly equally divided between the intervals of ≤10 weeks (22.5%), >10 to ≤12 weeks (24.6%); and >12 weeks to ≤14 weeks (19.4%).59 Notably, this showed that 47.1% of patients had received reinjections at median intervals of ≤12 weeks, which is shorter than the standard recommended interval for BoNT-A therapy for CD patients. Mean doses received for both dose groups (120 U and 240 U) were similar across all injection sections and interval groups.59 The mean changes from baseline in TWSTRS total scores in each interval group showed statistically significant improvements 4 weeks after each injection (p<0.0001) (Figure 1).59 In addition, there were no statistically significant differences in the overall occurrence of AEs between interval groups (Table 3).59 Increased antibody production occurred in three (1.3%) patients and had no correlation with dosing frequency during the extension phase.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Movement Disorders Center of Arizona, Scottsdale, AZ, USA.

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.

No MeSH data available.


Related in: MedlinePlus