Botulinum Toxin Type A Formulation Research Articles

Does injection pattern matter in upper face BoNT-A application? A prospective split-face andomized trial comparing linear and spot technique.

Although the efficacy of botulinum toxin type A (BoNT-A) has been shown to vary depending on injection layer, reconstitution volumes, and BoNT-A formulations, the impact of injection patterns has been rarely mentioned. This article compared the therapeutic effects in patients treated with BoNT-A with retrograde linear and traditional spot injection techniques. Twenty-eight participants were enrolled in a split-face, patient-blinded randomized clinical trial. Each patient received BoNT-A injected with linear injection technique on one side and with spot injection technique on the other side. Outcomes included the wrinkle improvement rates (WIR) of the two injection techniques determined by the wrinkle scores derived from Antera 3D camera, the muscle activity assessed via ultrasound, and patient-reported pain rating on a numeric pain rating scale (NRS). All participants completed the study. For forehead wrinkles, WIR on the linear side was significantly larger than that on the spot side at 1 week and 1 month (p<0.02). For glabellar wrinkles, WIR on the linear injection side was significantly larger than that on the spot side at 1 week (p=0.04). However, for periorbital wrinkles, WIR on the spot side was significantly larger than that on the linear side at 1 week (p<0.03). No significant difference was observed between the injection patterns in terms of muscle contraction and NRS scores. Compared with the traditional spot injection, the retrograde linear injection shows to be superior in reducing forehead lines and glabellar lines, but less effective in reducing periorbital lines when identical dosages were injected. chictr.org.cn: ChiCTR2100046880.

Botulinum toxin type A versus anticholinergics for cervical dystonia.

This is an update of a Cochrane Review first published in 2005. Cervical dystonia is the most common form of focal dystonia and is a highly disabling movement disorder, characterised by involuntary, usually painful, head posturing. Currently, botulinum toxin type A (BtA) is considered the first line therapy for this condition. Before BtA, anticholinergics were the most widely accepted treatment. To compare the efficacy, safety, and tolerability of BtA versus anticholinergic drugs in adults with cervical dystonia. We searched the Cochrane Movement Disorders' Trials Register to June 2003, screened reference lists of articles and conference proceedings to September 2018, and searched CENTRAL, MEDLINE, and Embase, with no language restrictions, to July 2020. Double-blind, parallel, randomised trials (RCTs) of BtA versus anticholinergic drugs in adults with cervical dystonia. Two review authors independently assessed records, selected included studies, extracted data using a paper pro forma, and evaluated the risk of bias and quality of the evidence. We resolved disagreements by consensus or by consulting a third review author. If enough data had been available, we were to perform meta-analyses using a random-effects model for the comparison of BtA versus anticholinergic drugs to estimate pooled effects and corresponding 95% confidence intervals (95% CI). The primary efficacy outcome was improvement in cervical dystonia-specific impairment. The primary safety outcome was the proportion of participants with any adverse event. We included one RCT of moderate overall risk of bias (as multiple domains were at unclear risk of bias), which included 66 BtA-naive participants with cervical dystonia. Two doses of BtA (Dysport; week 0 and 8; mean dose 262 to 292 U) were compared with daily trihexyphenidyl (up to 24 mg daily). The trial was sponsored by the BtA producer. BtA reduced cervical dystonia severity by an average of 2.5 points (95% CI 0.68 to 4.32) on the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) severity subscale 12 weeks after injection, compared to trihexyphenidyl. More participants reported adverse events in the trihexyphenidyl treatment group (76 events), compared with the BtA group (31 events); however, the difference in dropouts due to adverse events was inconclusive between groups. There was a decreased risk of dry mouth, and memory problems with BtA, but the differences were inconclusive between groups for the other reported side effects (blurred vision, dizziness, depression, fatigue, pain at injection site, dysphagia, and neck weakness). We found very low-certainty evidence that BtA is more effective, better tolerated, and safer than trihexyphenidyl. We found no information on a dose-response relationship with BtA, differences between BtA formulations or different anticholinergics, the utility of electromyography-guided injections, or the duration of treatment effect.

Impact of integrated upper limb spasticity management including repeat botulinum toxin type A (BoNT-A) injections on patient-centred goal attainment in real-life practice: results from the prospective, observational Upper Limb International Spasticity cohort study (ULIS-III) in a Russian subpopulation

To assess the longitudinal attainment of patient-centred and function related goals after integrated spasticity management including repeated cycles of botulinum toxin A type A (BoNT-A) injections in real life settings over a period of 2 years. The article presents analysis of the results within the subpopulation of patients from Russia. This international, multicentre, observational, prospective, longitudinal cohort study (registered at clinicaltrials.gov as NCT02454803) included patients ≥18 years old with upper-limb spasticity of any aetiology in whom a decision had already been made to inject any BoNT-A formulation commercially available in the Russi. The treatment outcomes were evaluated using the Upper Limb Spasticity Index, which combines the patient-centred Goal Attainment Scaling (GAS) with a set of targeted standardised measures to assess the neurological impairment. The extent of functional impairment was assessed using the DAS. 168 Russian patients from 7 sites with a mean age of 49.8 years participated in the study. The Russian subpopulation had some differences from the overall study population in baseline characteristics of patients and injection practices of BoNT-A treatment. During the study period, the majority of Russian patients received AboBoNT-A (Dysport) injections - 142 (85%) patients at cycle 1, while OnaBoNT-A (Botox) was used in 14 (8%) patients, and IncoBoNT-A (Xeomin) - in 12 (7%) patients. Higher doses of AboBoNT-A were observed compared to the overall population, mean doses of AboBoNT-A between cycles 1 and 4 were 909-934 U in the Russian patients and 814-859 U in the overall population. In general, patients of the Russian subpopulation successfully achieved their treatment goals. The mean cumulated GAS T-score over the study was 51.1±3.0, marginally exceeding the same parameter in the overall population (49.5±5.9). Across the 6 goal domains, cumulated GAS T-scores in Russian subpopulation were highest for the goals related to passive function and pain relief, with mean scores of 51.8±4.2 and 51.6±4.8, respectively. In the overall population cumulated GAS T-scores were highest for involuntary movements (mean 50.5±5.6) and pain relief (mean 50.4±6.2). The lowest GAS T-scores were for the treatment goals related to active function in both Russian subpopulation and overall population, the mean scores were 48.3±5.5 and 46.6±7.4 respectively. The study results also showed significant improvement in in terms of reduction of muscle tone according to MAS (Modified Ashworth Scale) and the extent of functional impairment according to DAS (Disability Assessment Scale). The results of this subgroup analysis on patients from Russia showed high effectiveness of repeated cycles of BoNT-A injections as part of the integrated upper limb spasticity management conducted in real life settings, both in terms of reduction of muscle tone and correction of functional impairment, which contributes to the successful achievement of the treatment goals. The right choice of individual patient-centred treatment goals and methods for assessing their achievement are important components of the treatment and rehabilitation process for patients with spastic paresis of the upper limb.

Botulinum toxin type A therapy for hemifacial spasm.

This is an update of a Cochrane Review, first published in 2005. Hemifacial spasm (HFS) is characterised by unilateral, involuntary contractions of the muscles innervated by the facial nerve. It is a chronic disorder, and spontaneous recovery is very rare. The two treatments routinely available are microvascular decompression and intramuscular injections with botulinum toxin type A (BtA). To compare the efficacy, safety, and tolerability of BtA versus placebo in people with HFS. We searched CENTRAL, MEDLINE, Embase, reference lists of articles, and conference proceedings in July 2020. We ran the electronic database search, with no language restrictions, in July 2020. Double-blind, parallel, randomised, placebo-controlled trials (RCTs) of BtA versus placebo in adults with HFS. Two review authors independently assessed records. We planned to select included studies, extract data using a paper pro forma, and evaluate the risk of bias. We resolved disagreements by consensus, or by consulting a third review author. We planned to perform meta-analyses. The primary efficacy outcome was HFS-specific improvement. The primary safety outcome was the proportion of participants with any adverse event. We found no parallel-group randomised controlled trials comparing BtA and placebo in HFS. We did not find any randomised trials that evaluated the efficacy and safety of botulinum toxin type A in people with hemifacial spasm, so we are unable to draw any conclusions. Observational data show a strong association between BtA treatment and symptom improvement, and a favourable safety profile. While it is unlikely that future placebo-controlled RCTs will evaluate absolute efficacy and safety, they should address relevant questions for both people with HFS (such as long-term effects, quality of life, and other patient-reported outcomes), and clinicians (such as relative effectiveness of different BtA formulations and schemes of treatment) to better guide clinical practice.).

Botulinum toxin type A therapy for cervical dystonia.

This is an update of a Cochrane Review first published in 2005. Cervical dystonia is the most common form of focal dystonia, and is a highly disabling movement disorder, characterised by involuntary, usually painful, head posturing. Currently, botulinum toxin type A (BtA) is considered the first line therapy for this condition. To compare the efficacy, safety, and tolerability of BtA versus placebo, in people with cervical dystonia. We searched Cochrane Movement Disorders' Trials Register, CENTRAL, MEDLINE, Embase, reference lists of articles, and conference proceedings in July 2020. All elements of the search, with no language restrictions, were last run in July 2020. Double-blind, parallel, randomised, placebo-controlled trials (RCTs) of BtA versus placebo in adults with cervical dystonia. Two review authors independently assessed records, selected included studies, extracted data using a paper pro forma, and evaluated the risk of bias. We resolved disagreements by consensus or by consulting a third review author. We performed meta-analyses using a random-effects model, for the comparison of BtA versus placebo, to estimate pooled effects and corresponding 95% confidence intervals (95% CI). We performed preplanned subgroup analyses according to BtA dose used, the BtA formulation used, and the use (or not) of guidance for BtA injections. The primary efficacy outcome was improvement in cervical dystonia-specific impairment. The primary safety outcome was the proportion of participants with any adverse event. We included nine RCTs, with moderate, overall risk of bias, that included 1144 participants with cervical dystonia. Seven studies excluded participants with poorer responses to BtA treatment, therefore, including an enriched population with a higher probability of benefiting from this therapy. Only one trial was independently funded. All RCTs evaluated the effect of a single BtA treatment session, using doses from 150 U to 500 U of onabotulinumtoxinA (Botox), 120 U to 240 U of incobotulinumtoxinA (Xeomin), and 250 U to 1000 U of abobotulinumtoxinA (Dysport). BtA resulted in a moderate to large improvement from the participant's baseline clinical status, assessed by the investigators, with a mean reduction of 8.09 points in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS total score) at week four after injection (95% CI 6.22 to 9.96; I² = 0%) compared to placebo. This corresponded, on average, to a 18.4% improvement from baseline. The mean difference (MD) in TWSTRS pain subscore at week four was 2.11 (95% CI 1.38 to 2.83; I² = 0%) compared to placebo. Overall, both participants and clinicians reported an improvement of subjective clinical status. It was unclear if dropouts due to adverse events differed (risk ratio (RR) 2.51; 95% CI 0.42 to 14.94; I² = 0%) However, BtA treatment increased the risk of experiencing an adverse event (R) 1.23; 95% CI 1.05 to 1.43; I² = 28%). Neck weakness (14%; RR 3.40; 95% CI 1.19 to 9.71; I² = 15%), dysphagia (11%; RR 3.19; 95% CI 1.79 to 5.70; I² = 0%), and diffuse weakness or tiredness (8%; RR 1.80; 95% CI 1.10 to 2.95; I² = 0%) were the most common treatment-related adverse events. Treatment with BtA resulted in a decreased risk of dropouts. We have moderate certainty in the evidence across all of the aforementioned outcomes, with the exception of subjective assessment and tolerability, in which we have high confidence in the evidence. We found no evidence supporting the existence of a clear dose-response relationship between BtA and improvement in cervical dystonia-specific impairment, a destinction between BtA formulations, or a variation with use of EMG-guided injection for efficacy outcomes. Due to clinical heterogeneity, we did not pool health-related quality of life data, duration of clinical effect, or the development of secondary non-responsiveness. We are moderately certain in the evidence that a single BtA treatment session resulted in a clinically relevant reduction of cervical dystonia-specific impairment, and pain, and highly certain that it is well tolerated, compared with placebo. There is moderate-certainty evidence that people treated with BtA are at an increased risk of developing adverse events, most notably, dysphagia, neckweakness and diffuse weakness or tiredness. There are no data from RCTs evaluating the effectiveness and safety of repeated BtA injection cycles. There is no evidence from RCTs to allow us to draw definitive conclusions on the optimal treatment intervals and doses, the usefulness of guidance techniques for injection, the impact on quality of life, or the duration of treatment effect.

Cervical dystonia — improving the effectiveness of botulinum toxin therapy

Cervical dystonia is the most frequent form of focal dystonia. It is characterised by involuntary muscular contractions resulting in abnormal head/neck and shoulder movements and postures, which can be associated with tremor and pain. Local intramuscular injections of botulinum toxin type A (BoNT-A) is the treatment of choice, being both effective and well-tolerated. However, a considerable number (c. 30%) of patients discontinue this treatment. The aim of this review was to analyse the factors possibly responsible for treatment failures of cervical dystonia (CD), with special regard to the new classification known as the 'Col-Cap' concept and non-motor symptoms. Several factors analysed in this review are responsible for effective treatment: proper diagnosis of dystonia and exclusion of pseudodystonias, correct recognition of dystonia pattern and identification of new patterns according to the Col-Cap concept, muscle selection and precise injections under electromyography (EMG) and/or ultrasonography (US) guidance. Furthermore, concomitant diagnosis and treatment of non-motor symptoms such as depression, anxiety, fatigue, sleep problems, phobias and stigmatisation are crucial in obtaining the best overall effect of the treatment. Primary and secondary immunisation and non-responsiveness seem to be marginal problems nowadays due to a low potential of new BoNT-A formulations to produce neutralising antibodies. There is a need for new and relevant scales combining the Col-Cap concept patterns with non-motor symptoms and quality of life. There is also a lack of specific rehabilitation protocols which could enhance BoNT-A treatment results.

Botulinum toxin type A therapy for cervical dystonia.

This is an update of a Cochrane Review first published in 2005. Cervical dystonia is the most common form of focal dystonia and is a highly disabling movement disorder characterised by involuntary, usually painful, head posturing. Currently, botulinum toxin type A (BtA) is considered the first line therapy for this condition. To compare the efficacy, safety, and tolerability of botulinum toxin type A (BtA) versus placebo in people with cervical dystonia. To identify studies for this review we searched Cochrane Movement Disorders' Trials Register, CENTRAL, MEDLINE, Embase, reference lists of articles and conference proceedings. All elements of the search, with no language restrictions, were run in October 2016. Double-blind, parallel, randomised, placebo-controlled trials (RCTs) of BtA versus placebo in adults with cervical dystonia. Two review authors independently assessed records, selected included studies, extracted data using a paper pro forma, and evaluated the risk of bias. We resolved disagreements by consensus or by consulting a third review author. We performed meta-analyses using a random-effects model for the comparison of BtA versus placebo to estimate pooled effects and corresponding 95% confidence intervals (95% CI). In addition, we performed preplanned subgroup analyses according to BtA dose used, the BtA formulation used, and the use or not of guidance for BtA injection. The primary efficacy outcome was improvement in cervical dystonia-specific impairment. The primary safety outcome was the proportion of participants with any adverse event. We included eight RCTs of moderate overall risk of bias, including 1010 participants with cervical dystonia. Six studies excluded participants with poorer responses to BtA treatment, therefore including an enriched population with a higher probability of benefiting from this therapy. Only one trial was independently funded. All RCTs evaluated the effect of a single BtA treatment session, using doses from 150 U to 236 U of onabotulinumtoxinA (Botox), 120 U to 240 U of incobotulinumtoxinA (Xeomin), and 250 U to 1000 U of abobotulinumtoxinA (Dysport).BtA was associated with a moderate-to-large improvement in the participant's baseline clinical status as assessed by investigators, with reduction of 8.06 points in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS total score) at week 4 after injection (95% CI 6.08 to 10.05; I2 = 0%) compared to placebo, corresponding on average to a 18.7% improvement from baseline. The mean difference (MD) in TWSTRS pain subscore at week 4 was 2.11 (95% CI 1.38 to 2.83; I2 = 0%). Overall, both participants and clinicians reported an improvement of subjective clinical status. There were no differences between groups regarding withdrawals due to adverse events. However, BtA treatment was associated with an increased risk of experiencing an adverse event (risk ratio (RR) 1.19; 95% CI 1.03 to 1.36; I2 = 16%). Dysphagia (9%) and diffuse weakness/tiredness (10%) were the most common treatment-related adverse events (dysphagia: RR 3.04; 95% CI 1.68 to 5.50; I2 = 0%; diffuse weakness/tiredness: RR 1.78; 95% CI 1.08 to 2.94; I2 = 0%). Treatment with BtA was associated with a decreased risk of participants withdrawing from trials. We have moderate certainty in the evidence across all of the aforementioned outcomes.We found no evidence supporting the existence of a clear dose-response relationship with BtA, nor a difference between BtA formulations, nor a difference with use of EMG-guided injection.Due to clinical heterogeneity, we did not pool data regarding health-related quality of life, duration of clinical effect, or the development of secondary non-responsiveness. We have moderate certainty in the evidence that a single BtA treatment session is associated with a significant and clinically relevant reduction of cervical dystonia-specific impairment, including severity, disability, and pain, and that it is well tolerated, when compared with placebo. There is also moderate certainty in the evidence that people treated with BtA are at an increased risk of developing adverse events, most notably dysphagia and diffuse weakness. There are no data from RCTs evaluating the effectiveness and safety of repeated BtA injection cycles. There is no evidence from RCTs to allow us to draw definitive conclusions on the optimal treatment intervals and doses, usefulness of guidance techniques for injection, the impact on quality of life, or the duration of treatment effect.

Patient satisfaction with different botulinum toxin type A formulations in the treatment of moderate to severe upper facial rhytids

Background: The clinical characteristics of botulinum toxin type A (BoNTA) depend on the formulation used. Objective: To evaluate whether switching BoNTA formulations affects patient satisfaction. Methods: Forty patients enrolled and all were satisfied or extremely satisfied with Allergan BoNTA (BoNTA–Allergan) treatment in the glabellar±crow's feet±forehead area(s) in the preceding 6 months. Once improvement from this previous treatment had started to diminish, treatment was replicated using Ipsen BoNTA (BoNTA–Ipsen) at a 1:2.5 dose ratio. Results: The incidence of patients rating treatment as effective or very effective in making them look younger, look rested, and look less stressed was significantly higher with BoNTA–Allergan than BoNTA–Ipsen – 83% versus 36%, 90% versus 39%, and 83% versus 33%, respectively – even though evaluations were performed a mean of 20 weeks after BoNTA–Allergan treatment and only 16 weeks after BoNTA–Ipsen treatment. The incidence of patients who were satisfied or extremely satisfied was 100% (BoNTA–Allergan) versus 31% (BoNTA–Ipsen). BoNTA–Allergan was preferred by 69% of patients. Conclusions: Efficacy, satisfaction, and product preference ratings strongly favor the use of BoNTA–Allergan over BoNTA–Ipsen in the treatment of upper facial lines. Many patients who are satisfied with BoNTA–Allergan treatment become less satisfied if they are switched to BoNTA–Ipsen.

Formation of neutralizing antibodies in patients receiving botulinum toxin type a for treatment of poststroke spasticity: A pooled-data analysis of three clinical trials

Objective: The purpose of this study was to investigate the incidence of neutralizing antibody (NAb) formation in patients with poststroke spasticity treated with a specific formulation of botulinum toxin type A (BoNTA). Methods: Data from 3 previous clinical trials of BoNTA in patients with upper and/or lower limb spasticity were pooled and evaluated. Study 1 was a randomized, double-blind, placebo-controlled, multicenter trial of BoNTA in patients aged ≥21 years who had experienced a stroke >6 months before the initiation of the study. Study 2 was an open-label extension of study 1. Study 3 was a randomized, double-blind, multicenter trial of a specific BoNTA formulation in patients aged ≥ 21 years who had experienced a stroke ≥6 weeks before study entry. Patients with a fixed contracture of the studied limb were excluded from participation in studies 1 and 2. Serum samples were obtained from each patient before each BoNTA treatment and at the end of each study. The mouse protection assay (MPA) was used for detection of NAbs to BoNTA in serum. Results: A total of 235 individual patients with post-stroke spasticity were enrolled in the 3 trials, including 126, 111 (all of whom participated in study 1), and 109 in studies 1, 2, and 3, respectively. Study 1 had an equal (50.0%) distribution of male and female patients (63/63). The distribution of male and female patients was 56 (50.5%) and 55 (49.5%), respectively, in study 2, and 55 (50.5%) and 54 (49.5), respectively, in study 3. The mean (SD) ages of patients in studies 1, 2, and 3 were 61.4 (13.8), 61.5 (14.1), and 58.5 (13.9) years, respectively. The MPA was used for detection of NAbs to BoNTA in the serum samples of 191 patients, including 64 from study 1, 111 from study 2 (55 of these patients were placebo recipients and 56 received their first BoNTA injection in study 1), and 72 (a sample was not obtained for 1 patient who had not received an injection) from study 3. The median number of BoNTA treatments received by these patients was 2 (range, 1–4 treatments) over a period lasting from 12 to 42 weeks. The mean dose of BoNTA was 241 U (range, 100–400 U), with a maximum dose of 960 U in any 1 patient. NAbs to BoNTA were detected in the serum sample of 1/191 (0.5%) patient who had participated in studies 1 and 2. Based on muscle-tone scores (3 and 4 for wrist and fingers, respectively) on a 5-point Ashworth Scale (0 = none to 4 = severe), the patient did not appear to exhibit a clinical response to BoNTA at any time during the studies. Conclusion: Formation of NAbs was rare (1/191) in this group of adults with poststroke spasticity from three 12- to 42-week clinical trials who received ≥1 treatment with a specific BoNTA formulation at doses ranging from 100 to 400 U.

PR_045: Migration Associated With Adverse Effect of Botulinum Toxin Type A Distant From Injection Site: A Preliminary Study

Objective: To investigate the incidence of clinical events linked to migration of botulinum toxin type A (BTX-A) from the injection site. Design: Single-center, cohort study. Setting: In- and outpatient rehabilitation center. Participants: Patients exhibiting symptoms of spasticity. Intervention: Patients were injected with BTX-A. Main Outcome Measures: Patients who reported adverse effects distant from the injection site underwent a single-fiber electromyography (SFEMG) examination to investigate neuromuscular transmission (jitter) at the extensor digitorum communis. A patient with severe motor dysfunction underwent a muscle biopsy. Results: A total of 453 BTX-A injection sessions (413 Botox, 40 Dysport) over a 9-month period were administered for the treatment of spasticity. A total of 5 patients, all receiving Dysport (1000−1500U), presented with adverse effects distant from the injection site, including diplopia, fatigue, and diffuse muscle weakness with severe functional impairment. No adverse effects were observed in the Botox group. On average, these adverse effects first appeared 9.5 days postinjection and lasted 12.8 weeks. 4 of these 5 patients demonstrated abnormal jitter in muscles distant from the injection site, as detected by SFEMG, at an average of 30.5 days postinjection. Atrophic fibers were observed in the single biopsy, suggesting moderate denervation without reinnervation in a distant muscle from the injection. Conclusions: In this clinical setting, Dysport-treated patients reported adverse effects consistent with unwanted toxin migration beyond the targeted site. These distant adverse effects were not reported in the Botox-treated patients. Unwanted toxin migration from the original site was confirmed by SFEMG that displayed abnormal muscle jitter. These findings suggest that different BTX-A formulations have distinct clinical and migratory profiles and require further study and analysis.

Botulinum toxin type A therapy for cervical dystonia

Cervical dystonia is characterized by involuntary posturing of the head and frequently is associated with neck pain. Disability and social withdrawal are common. In recent years, Botulinum toxin Type A (BtA) has become the first line therapy. However its true efficacy, in particular the potential effect size, is still unclear. To determine whether botulinum toxin (BtA) is an effective and safe treatment for cervical dystonia. We searched the Cochrane Movement Disorders Group trials register (June 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2003, MEDLINE (1977 to June 2003), EMBASE (1977 to June 2003) and reference lists of articles. We also contacted drug manufacturers and researchers in the field. Randomised studies comparing BtA with placebo in adults with cervical dystonia. Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. We found thirteen high quality eligible studies. They were short term (6 to 16 weeks). Eight trials, enrolling 361 patients, used the BtA formulation Botox(r) and five, enrolling 319 patients, used the BtA formulation Dysport. The dose and technique of administration varied significantly between studies.Meta-analysis showed statistically and clinically significant improvements on objective rating scales: (Peto OR 4.31; 95% confidence interval (CI) 2.68 to 6.94) and subjective rating scales (Peto OR 6.58; 95% CI 4.55 to 9.54); and for pain relief in subjective scales (Peto OR 11.92; 95% CI 6.32 to 22.5). However, for many of the outcomes, we could use data from only a few studies. Only adverse events clearly associated with the mechanism of action of BtA were more frequent in the treatment group. These included neck weakness, dysphagia, dry mouth/sore throat and voice changes/hoarseness. Sub-group and sensitivity analyses showed a clear dose-response relationship for subjective and objective benefit and for frequency and severity of adverse events. Indirect comparisons between trials that used Dysport against placebo and trials that used Botox against placebo showed no significant differences between Dysport and Botox in terms of benefits or adverse events. A single injection cycle of BtA is effective and safe for treating cervical dystonia. Enriched trials (using patients previously treated with BtA), suggest that further injection cycles continue to work for most patients.

Botulinum toxin type A versus anticholinergics for cervical dystonia

Cervical dystonia is the most common form of focal dystonia. It is characterized by involuntary posturing of the head and frequently is associated with neck pain. Disability and social withdrawal are common. Most cases are idiopathic and generally cervical dystonia is a life-long disorder. Botulinum toxin Type A (BtA) is now the first line therapy. Before BtA, anticholinergics were the most widely accepted treatment, so it is important to understand how these two treatments compare. To compare the clinical efficacy and safety of BtA versus anticholinergic drugs in the treatment of cervical dystonia. We searched the Cochrane Movement Disorders Group trials register (June 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2, 2003), MEDLINE 1977 to June 2003), EMBASE (1977 to June 2003) and reference lists of articles. We also contacted manufacturers and researchers in the field. Randomised studies comparing BtA versus any anticholinergic drug for the treatment of cervical dystonia. Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. We found only one trial suitable for inclusion and accordingly no meta-analysis was performed. It compared BtA versus trihexyphenidyl in 66 patients with cervical dystonia. Although this was a relatively small trial with short duration, the results can probably be generalized for the population, since the trial appears to be unbiased and produced clear clinically significant results. The results favoured BtA, and the difference was similar in size to that obtained in a systematic review comparing BtA with placebo. BtA was better tolerated. The available evidence suggests that BtA injections provide more objective and subjective benefit than trihexyphenidyl to patients with cervical dystonia. We could not draw any conclusions about other anticholinergic drugs. Future trials should explore the role of anticholinergic drugs in patients that do not get benefit with BtA.