Botulinum Toxin Therapy for Cervical Dystonia: The Science of Dosing

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 BOTOXH Efficacy (CD PROBE), may help clarify this question of optimal dosing intervals for BoNT-A in CD.

Effective botulinum toxin injection guide for treatment of cervical dystonia

“…Two‐thirds to three‐quarters of shortened SCM patients reportedly experience severe pain in the neck, while other factors associated with the disability are fatigue, anxiety, depression, and decreased self‐efficacy (van den Dool et al, ). Oral medications such as baclofen, benzodiazepines, and anticholinergic agents are common treatments for shortened SCM, but they are associated with many side effects (Evidente and Pappert, ). As an alternative to such oral medications, BoNT injection has fewer side effects and confers greater improvements with regard to range of motion, correct posture, and pain management (Comella, ).…”

“…Most studies have obtained significant improvements in head posture, pain, and quality of life with these therapies, with most patients reporting benefits of injection treatments (Nilesh and Mukherji, ). BoNT enhances the elasticity of the SCM, and its relieving effects appear immediately upon injection (Nilesh and Mukherji, ; Evidente and Pappert, ).…”

“…While BoNT injections have been used in various clinical fields for over 25 years, this treatment remains challenging due to complex factors that need to be considered before its application, including regarding side effects (Evidente and Pappert, ). One common and severe side effect resulting from inaccurate injection and excessive diffusion of BoNT is dysphagia, whose reported incidence ranges from 10% to 40% (Hong et al, ).…”

Therapeutic Uses of Botulinum Toxin

“…The FDA approved the use of botulinum toxin A for cervical dystonia in 2000 and it is the first-line treatment for this condition. However, despite the use of botulinum toxin in cervical dystonia for over 20 years, there are still unanswered questions surrounding optimal dosing and dosing intervals [31]. Treatment failure is reported in 20% of patients [32].…”

Cervical dystonia — improving the effectiveness of botulinum toxin therapy

“…Double-blind, randomised clinical, as well as open, studies have shown that 50-85% of patients demonstrate a significant improvement [7][8][9][10][11][12][13][14][15]. A considerable number (c. 30%, range 19-46%) of patients discontinue treatment once it appears to be ineffective [16][17][18][19][20].…”