Patient perspectives on the therapeutic profile of botulinum neurotoxin type A in cervical dystonia.

BACKGROUND: Botulinum neurotoxin type A (BoNT-A) is an effective pharmacological treatment for the management of cervical dystonia (CD) that requires repeated administration at variable intervals. We explored patient perceptions of the impact of CD and the waning of BoNT-A therapeutic effects. METHODS: An internet-based survey was conducted through Carenity, a global online patient community, from May to September 2019. Eligible respondents were adults with CD who had ≥ 2 previous BoNT-A injections. RESULTS: 209 respondents (81% females; mean age of 49.7 years) met the screening criteria. The mean BoNT-A injection frequency was 3.9 injections/year. The mean reported onset of BoNT-A therapeutic effect was 11.7 days and the time to peak effect was 4.5 weeks. Symptom re-emergence between injections was common (88%); the time from injection to symptom re-emergence was 73.6 days (~ 10.5 weeks). Treatment was not reported to completely abolish symptoms, even at peak effect. However, symptom severity was rated (0 = no symptoms; 10 = very strong symptoms) as lowest at the peak of treatment effects (mean scores ~ 3/10), increasing as the effects of treatment start waning (~ 5.5/10) and was strongest one day before the next session (~ 7-8/10). The impact of CD on quality of life followed the same 'rollercoaster' pattern. CONCLUSIONS: This survey highlights the burden of CD symptoms, even in patients undergoing regular treatment. Symptom re-emergence is common and has significant impact on daily activities and quality of life. Greater awareness of the therapeutic profile of BoNT-A treatment should lead to better informed therapeutic discussions and planning.

Cumulative effects of long-term treatment with abobotulinumtoxinA in cervical dystonia: Findings from a prospective, observational study.

OBJECTIVE: Patients with cervical dystonia (CD) require regular injections of botulinum neurotoxin type A (BoNT-A) to maintain treatment effectiveness. In this secondary analysis of a large routine-practice study, we assessed the response to abobotulinumtoxinA over repeated cycles and compared the responses of patients previously naïve to BoNT treatment to those already treated with BoNT-A. METHODS: INTEREST IN CD2 was a prospective, 3-year, observational study following CD patients treated with BoNT-A. Patients were assessed at each injection visit using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and Tsui scale; patient satisfaction with symptom control (previous cycle) was recorded. RESULTS: This analysis included 466 patients treated with abobotulinumtoxinA over 3 years. TWSTRS-Total scores continually decreased; the mean ± SD reduction from baseline to 36 months was -7.4 ± 11.9. BoNT-naïve patients tended to show greater reductions in TWSTRS scores than already treated patients, particularly in the first 6 months. Incremental improvements were also seen in Tsui-tremor scores. Overall levels of patient satisfaction at peak effect (84.1-91.2%) were consistently higher than at the end of cycle (47.2-53.2%). The most frequently reported adverse events were dysphagia (6.8%) and muscular weakness (3.7%). CONCLUSIONS: These data support the long-term effectiveness and safety of abobotulinumtoxinA in a real-world setting.

Impact of abobotulinumtoxinA on the clinical features of cervical dystonia in routine practice.

INTRODUCTION: The efficacy and safety of abobotulinumtoxinA in the management of cervical dystonia has been established in randomized, controlled trials that use a selected trial population. In this meta-analysis of observational data, we evaluated the real-life effectiveness of abobotulinumtoxinA as delivered in routine clinical practice. METHODS: Meta-analysis of patient-level data for adult patients with cervical dystonia treated with abobotulinumtoxinA from three prospective, multicenter, observational studies (NCT01314365, NCT00833196 and NCT01753349). RESULTS: We report data for patients treated with abobotulinumtoxinA over one injection cycle at 181 neurology centers in 35 countries. CD clinical features as assessed by Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total scores (N = 920) significantly reduced by a mean [95%CI] of -12.9 [-13.9, -11.8] points at Week 4 (N = 449) and -3.2 [-3.8, -2.7] points at the end of the injection cycle (N = 890). All three TWSTRS domains (symptom severity, disability and pain) contributed to the overall improvement. Patients were generally content with symptom control at peak effect of the treatment cycle, with 86% reporting overall satisfaction. CONCLUSION: Findings from this meta-analysis of observational studies confirm the effectiveness of abobotulinumtoxinA in routine practice. Despite inclusion of a broader population sample, the magnitude of improvements observed is consistent with that seen in the pivotal, randomized controlled trials.

Correction to: How satisfied are cervical dystonia patients after 3 years of botulinum toxin type A treatment? Results from a prospective, long-term observational study.

The article How satisfied are cervical dystonia patients after 3 years of botulinum toxin type A treatment?

How satisfied are cervical dystonia patients after 3 years of botulinum toxin type A treatment? Results from a prospective, long-term observational study.

BACKGROUND: Patients with cervical dystonia (CD) typically require regular injections of botulinum toxin to maintain symptomatic control. We aimed to document long-term patient satisfaction with CD symptom control in a large cohort of patients treated in routine practice. METHODS: This was a prospective, international, observational study (NCT01753349) following the course of adult CD treated with botulinum neurotoxin type A (BoNT-A) over 3 years. A comprehensive clinical assessment status was performed at each injection visit and subjects reported satisfaction in two ways: satisfaction with symptom control at peak effect and at the end of treatment cycle. RESULTS: Subject satisfaction remained relatively stable from the first to the last injection visit. At 3 years, 89.9% of subjects reported satisfaction with symptom control at peak effect and 55.6% reported satisfaction with symptom control at end of treatment cycle. By contrast, objective ratings of CD severity showed an overall reduction over 3 years. Mean ± SD Toronto Western Spasmodic Rating Scale (TWSTRS) Total scores (clinician assessed at end of treatment cycle) decreased from 31.59 ± 13.04 at baseline to 24.49 ± 12.43 at 3 years (mean ± SD reduction from baseline of - 6.97 ± 11.56 points). Tsui scale scores also showed gradual improvement; the percent of subjects with a tremor component score of 4 reduced from 12.4% at baseline to 8.1% at 3 years. CONCLUSIONS: Despite objective clinical improvements over 3 years, subject satisfaction with symptom control remained relatively constant, indicating that factors other than symptom control also play a role in patient satisfaction.

Spectrum of practice in the routine management of cervical dystonia with abobotulinumtoxinA: findings from three prospective open-label observational studies.

BACKGROUND: Cervical dystonia is a heterogeneous disorder with several possible presentations, for which first-line therapy is often botulinum toxin (BoNT). In routine clinical practice the success of each BoNT injection is dependent on several variables, including individual presentation and injection technique. Large multicenter, observational studies provide important information on individualized administration strategies that cannot be otherwise ascertained from controlled clinical trials. In this meta-analysis of patient level data, we aimed to evaluate the clinical characteristics of patients with cervical dystonia undergoing routine treatment with botulinum toxin, specifically abobotulinumtoxinA. We also aimed to characterize current abobotulinumtoxinA injection techniques and parameters and to explore international differences in patient presentation and treatment. METHODS: This was a meta-analysis of baseline data from three prospective, international, multicenter, observational studies (NCT01314365, NCT00833196 and NCT01753349) of botulinum toxin treatment for the routine management of adult cervical dystonia. RESULTS: Data presented illustrate the significant heterogeneity of CD presentation in routine practice. Most subjects presented with a complex pattern of dystonic movements and the majority had additional components of shoulder elevation, tremor and/or jerk. Dosing was generally in accordance with that recommended in the abobotulinumtoxinA prescribing information, although the range of dosing also indicates that injections are tailored to individual presentation. Sub-group analyses at the country level revealed distinct differences in injection practice. CONCLUSIONS: This meta-analysis is based on the largest dataset of subjects with cervical dystonia studied to date. The heterogeneity revealed in our baseline findings support the need to develop consistent, practical and comprehensive best practice guidelines.

INTEREST IN CD2, a global patient-centred study of long-term cervical dystonia treatment with botulinum toxin.

BACKGROUND: Longitudinal cohort studies provide important information about the clinical effectiveness of an intervention in the routine clinical setting, and are an opportunity to understand how a population presents for treatment and is managed. METHODS: INTEREST IN CD2 (NCT01753349) is a prospective, international, 3-year, longitudinal, observational study following the course of adult idiopathic cervical dystonia (CD) treated with botulinum neurotoxin type A (BoNT-A). The primary objective is to document long-term patient satisfaction with BoNT-A treatment. Here we report baseline data. RESULTS: This analysis includes 1036 subjects (67.4% of subjects were female; mean age was 54.7 years old; mean TWSTRS Total score was 31.7). BoNT-A injections were usually given in line with BoNT-A prescribing information. The most commonly injected muscles were splenius capitis (87.3%), sternocleidomastoid (82.6%), trapezius (64.3%), levator scapulae (40.9%) and semispinalis capitis (26.9%); 35.5% of subjects were injected using a guidance technique. Most subjects (87.8%) had been previously treated with BoNT-A (median interval between last pre-study injection and study baseline was 4 months); of these 84.8% reported satisfaction with BoNT-A treatment at peak effect during their previous treatment cycle and 51.5% remained satisfied at the end of the treatment. Analyses by geographical region revealed heterogeneity in the clinical characteristics and BoNT-A injection practice of CD subjects presenting for routine treatment. CONCLUSIONS: These baseline analyses provide sizeable data regarding the epidemiology and clinical presentation of CD, and demonstrate an international heterogeneity of clinical practice. Future longitudinal analyses of the full 3-year study will explore how these factors impact treatment satisfaction.

Factors influencing secondary non-response to botulinum toxin type A injections in cervical dystonia.

BACKGROUND: The development of secondary non-response (SNR) to botulinum neurotoxin type-A (BoNT-A) is considered a key issue in the management of cervical dystonia (CD). This case-controlled study was performed to systematically identify factors influencing SNR during BoNT-A therapy. METHODS: This was a retrospective, international, non-interventional study of CD patients. Patients with SNR were matched with up to three responder patients (control) on the basis of duration of therapy and number of injection cycles. Factors influencing the development of SNR were screened using a univariate logistic regression model and confirmed using a multivariate conditional logistic regression model. RESULTS: 216 patients were enrolled, and 201 (SNR = 52; responder = 149) were matched and subdivided into blocks (doublets, triplets or quadruplets). At baseline, a significantly higher proportion of SNR patients had received previous or concomitant therapies (p = 0.038) and surgery for CD (p = 0.007) compared with controls. Although disease severity at onset was similar between groups, a significantly higher proportion of SNR patients experienced severe CD at the time of SNR compared with controls at the last documented visit. Multivariate analyses identified five factors that were significantly associated in predicting SNR (odds ratio [OR] > 1 indicated higher chances for being SNR): previous surgical procedure for CD (OR 9.8, p = 0.013), previous BoNT-A related severe adverse event (AE) (OR 5.6 p = 0.027), physical therapy (OR 4.6, p = 0.028), neuroleptic use (OR 3.3, p = 0.019) and average BoNT-A dose (OR 2.7, p = 0.010). CONCLUSIONS: These findings suggest that SNR may not reflect true pharmacological resistance to BoNT-A therapy, but may be related to underlying disease severity.