Search

Andrew Thach,1 Jessie Sutphin,2 Joshua Coulter,2 Colton Leach,2 Eric Pappert,3 Carol Mansfield2 1Health Economics and Outcomes Research, Sunovion Pharmaceuticals Inc., Marlborough, MA, USA; 2Health Preference Assessment, RTI Health Solutions, Research Triangle Park, NC, USA; 3Medical Affairs, Sunovion Pharmaceuticals Inc., Marlborough, MA, USACorrespondence: Andrew ThachHealth Economics and Outcomes Research, Sunovion Pharmaceuticals Inc., 84 Waterford Dr, Marlborough, MA 01752, USATel +1 774-369-7123Email andrew.thach@sunovion.comIntroduction: Several on-demand treatments are available for management of “OFF” episodes in patients with Parkinson’s disease (PD). We evaluated patients’ preferences for features of theoretical on-demand treatment options.Methods: In a discrete choice experiment, US adults with self-reported PD of ≥ 5 years, or < 5 years with “OFF” episodes, taking oral carbidopa/levodopa, selected between pairs of theoretical on-demand treatments that varied by mode of administration (with and without mode-specific adverse events [AEs]), time to FULL “ON,” duration of “ON,” and out-of-pocket cost for a 30-day supply. Data were analyzed with a random parameters logit model; results were used to calculate relative importance of treatment attributes, preference shares, and willingness to pay.Results: Among 300 respondents, 98% had “OFF” episodes. Across the range of attribute levels included in the survey, avoiding $90 cost was most important to respondents, followed by a preferable mode of administration with associated AEs and decreasing time to FULL “ON.” Duration of “ON” was relatively less important. On average, respondents preferred a theoretical dissolvable sublingual film versus other theoretical treatments with alternative modes of administration. Respondents were willing to pay $28–$52 US dollars to switch from least- to more-preferred mode of administration with associated AEs, $58 to reach FULL “ON” in 15 versus 60 min, and $9 to increase duration of FULL “ON” from 1 to 2 h.Conclusion: Respondents with PD valued lower out-of-pocket cost and a sublingual mode of administration with its associated AEs when choosing an on-demand treatment for “OFF” episodes.Keywords: apomorphine sublingual film, discrete choice experiment, “OFF” episode, Parkinson’s disease, patient preference

Additional file 1: Figure S1. Linear regression analyses of relationship between PDQ-39 dimensions and average hours of daily “OFF” time. (a) Mobility, (b) Activities of daily living, (c) Emotional well-being, (d) Stigma, (e) Social support, (f) Cognitions, (g) Communication, and (h) Bodily discomfort. CI confidence interval; PDQ-39 39-Item Parkinson’s Disease Questionnaire.

Background: XCiDaBLE is a large, prospective, observational “naturalistic” study evaluating Xeomin® for Cervical Dystonia or BLEpharospasm in the United States. We report the interim results from the blepharospasm cohort of XCiDaBLE. Methods: Subjects (≥18 years old) with blepharospasm were followed for two treatment cycles of incobotulinumtoxinA and monitored for 4 weeks after injection via interactive voice/web response system (IVRS/IWRS). The investigator‐reported scale includes the Clinical Global Impression Scale‐Severity subscale (CGI‐S). Patient‐reported outcome measures include the Patient Global Impression Scale‐Severity (PGI‐S) and ‐Improvement (PGI‐I) subscales, Jankovic Rating Scale (JRS), SF‐12v2® health survey, and Work Productivity and Activity Impairment questionnaire. Subjects are seen by the investigator at baseline (including the first injection), during the second injection, and at a final study visit (12 weeks after the second injection). Results: One hundred seventy subjects were included in this interim analysis. The majority of subjects were female (77.1%) and white (91.8%), and had previously been treated with botulinum toxins (96.5%). The mean total dose (both eyes) was 71.5 U of incobotulinumtoxinA for the first injection. PGI‐S, PGI‐I, and JRS scores were significantly improved 4 weeks after treatment (all p, Tremor and Other Hyperkinetic Movements, Tremor and Other Hyperkinetic Movements

The objective of this study was to compare efficacy, safety, and duration of botulinum toxin type A (BoNT-A) and type B (BoNT-B) in toxin-naive cervical dystonia (CD) subjects. BoNT-naive CD subjects were randomized to BoNT-A or BoNT-B and evaluated in a double-blind trial at baseline and every 4-weeks following one treatment. The primary measure was the change in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) from baseline to week 4 post-injection. Secondary measures included change in TWSTRS-subscale scores, pain, global impressions, and duration of response and safety assessments. The study was designed as a noninferiority trial of BoNT-B to BoNT-A. 111 subjects were randomized (55 BoNT-A; 56 BoNT-B). Improvement in TWSTRS-total scores 4 weeks after BoNT-B was noninferior to BoNT-A (adjusted means 11.0 (SE 1.2) and 8.8 (SE 1.2), respectively; per-protocol-population (PPP)). The median duration of effect of BoNT-A and BoNT-B was not different (13.1 vs. 13.7 weeks, respectively; P-value = 0.833; PPP). There were no significant differences in the occurrence of injection site pain and dysphagia. Mild dry mouth was more frequent with BoNT-B but there were no differences for moderate/severe dry mouth. In this study, both BoNT-A and B were shown to be effective and safe for the treatment of toxin-naive CD subjects.

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., Tremor and Other Hyperkinetic Movements, Tremor and Other Hyperkinetic Movements

Objective: To evaluate the safety and efficacy of repeated doses of botulinum toxin type B (BoNT-B) in patients with cervical dystonia (CD) previously naive to BoNT. Methods: BoNT-naive CD patients completing a double-blind, comparator (BoNT-A vs. BoNT-B) phase continued in this open-label (OL) extension study. All OL patients received 10,000 U BoNT-B. Investigators could then modify dose by 5000 U increments/decrements during the subsequent 5 sessions (range 5000–25,000 U). Efficacy was assessed via Patient Global Visual Analogue Scale (VAS), and safety by evaluating adverse events (AEs), clinical laboratory data and vital signs. Results: 94 patients (45 and 49 had received BoNT-B and BoNT-A, respectively, during the previous double-blind study) were enrolled. 55 patients (58%) completed 6 OL treatment sessions (TS). Reasons for withdrawal included: AE (n=4); transportation/lost to follow-up (n=11); lack of efficacy (n=9); subject/sponsor decision (n=11); or other (n=4). Mean BoNT-B dose at TS 6 was 15,170 U (range 5000–25,000 U). BoNT-B demonstrated statistically significant benefit at Week 4 in the Patient Global VAS following each TS injection. No drug-related serious AEs were reported. Four subjects experienced 9 AEs leading to withdrawal: only dry mouth in 1 subject and fatigue, anorexia, influenza-like illness, and nausea in another subject were considered study drug-related. Moderate or severe dysphagia and dry mouth occurred in 9.6% and 16.0% of patients, respectively. No clinically significant changes in laboratory values or vital signs occurred. Conclusions: Repeated administration of BoNT-B provided persistent benefit and was well-tolerated in patients with CD previously naive to BoNT treatment. Supported by Eisai Europe Ltd.

Objective : To evaluate the long-term safety and efficacy of repeated doses of botulinum toxin type B (BoNT-B) in patients with cervical dystonia (CD) previously naive to BoNT-B but exposed to BoNT-A. Methods : BoNT-B-naive CD patients previously exposed to BoNT-A were enrolled in this 2-year open-label study. The initial BoNT-B dose was 10,000 U and thereafter Investigators could increase/decrease the dose (maximum 25,000 U). Efficacy was assessed via a Patient Global Visual Analogue Scale (VAS) and a Treatment Assessment Scale (TAS). Safety was assessed by evaluating adverse events (AEs), clinical laboratory data and vital signs. Results : 130 BoNT-B naive patients (67 BoNT-A-resistant and 63 BoNT-A-non resistant) were enrolled. The reasons for withdrawal during the 7 sessions included: AE ( n =7), removal of consent ( n =15), failure to respond ( n =18), protocol violation ( n =1), study discontinuation ( n =5) and other ( n =6). The mean dose of BoNT-B at session 7 was 17,593U (range 10,000–25,000 U). BoNT-B demonstrated a statistically significant benefit at Week 4 in the Patient Global VAS and the TAS following each injection throughout the 2 years. No study drug-related serious AEs were reported. Moderate/severe dysphagia, xerostomia and injection site pain occurred after at least one injection in 7.7%, 23.8% and 3.1% of patients, respectively, for the first 7 treatment sessions (most after injections 1–3). Four treatment-related AEs caused withdrawal. No clinically significant changes in laboratory values or vital signs occurred. Conclusions : Repeated administration of BoNT-B therapy in CD patients who were previously naive to BoNT-B but not BoNT-A was well-tolerated and provided long-term benefit. Supported by Eisai Europe Ltd.