Showing papers by "William G. Ondo published in 2018"
TL;DR: Consensus recommendations based on clinical practice are presented, including when to use oral iron or IV iron, and recommendations on repeated iron treatments.
195 citations
TL;DR: BoNT-A effectively and safely improved sleep bruxism in this placebo-controlled pilot trial and provides Class II evidence that botulinum injections into the masseter and temporalis muscles improve subjective Bruxism and painful symptoms associated with sleep bruXism.
Abstract: Objectives To test the safety and efficacy of onabotulinum toxin-A (BoNT-A) injections into the masseter and temporalis muscles in patients with symptomatic sleep bruxism. Methods Participants 18 to 85 years old with clinically diagnosed sleep bruxism confirmed by polysomnography were enrolled in this randomized, placebo-controlled, 1:1, parallel-design trial with open-label extension. Participants were injected with BoNT-A 200 units (60 into each masseter and 40 into each temporalis) or placebo and were evaluated at 4 to 8 weeks after the initial treatment visit. The primary efficacy endpoint was clinical global impression (CGI), and the secondary efficacy endpoint was a visual analog scale (VAS) of change in bruxism and in pain at 4 to 8 weeks after injection. Exploratory endpoints included modified Montreal Bruxism Questionnaire, Headache Impact Test-6, total Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Self-Rated Anxiety Scale, and polysomnography data, including EMG recordings of the masseter and temporalis muscle bruxing events. Adverse events were recorded. Results Thirty-one participants were recruited and 23 were randomized (19 female, age 47.4 ± 16.9 years). All 13 randomized to BoNT-A and 9 of 10 randomized to placebo completed the study. CGI ( p p Conclusions BoNT-A effectively and safely improved sleep bruxism in this placebo-controlled pilot trial. A large multicenter trial is needed to confirm these encouraging data. ClinicalTrials.gov identifier NTC00908050. Class of evidence This study provides Class II evidence that botulinum injections into the masseter and temporalis muscles improve subjective bruxism and painful symptoms associated with sleep bruxism.
50 citations
01 Jan 2018
TL;DR: Opioid use in selected patients with refractory RLS may be life‐transforming with favorable risk‐benefit ratio, and the basic science and clinical evidence in support of their use are summarized.
Abstract: Restless legs syndrome (RLS) is a distinct disorder, differing from chronic pain in many ways. Refractory RLS is characterized by unresponsiveness to dopamine agonists or alpha-2-delta ligands due to inadequate efficacy, augmentation, or adverse effects. This may result in severely impaired quality of life, profound insomnia, and suicidal depression. Opioid therapy is a mainstay in the management of these patients. This article summarizes the basic science and clinical evidence in support of their use, including the positive result of a large controlled multicenter study of 306 subjects, and outlines an approach to their use in clinical practice. Treatable explanations for RLS refractoriness, such as low iron stores, and other therapeutic options, such as combination therapy, should be considered before prescribing opioids. The agents most commonly used are oxycodone and methadone, but tramadol, codeine, morphine, and hydrocodone can also be considered. Controlled-release medication should be used for evening dosage and short-acting drugs, if needed, during the day. Effective doses are considerably lower than used for chronic pain (oxycodone 10-30 mg daily; methadone 5-20 mg daily) and the risk of opioid use disorder is relatively low. However, sensible precautions should be undertaken, including assessing opioid risk with standard questionnaires, using an opioid contract, using urine drug screens, consulting state prescription drug monitoring programs, and frequent reevaluation of effectiveness and side effects. Opioid use in selected patients with refractory RLS may be life-transforming with favorable risk-benefit ratio.
39 citations
TL;DR: Although VMAT2-inhibitors are now established as first-line treatment for tardive dyskinesia, not all patients respond to, or tolerate them, and better placebo controlled trials are needed before definitive recommendations can be made.
7 citations
Journal Article•
TL;DR: These results confirm the safety outcomes seen in the ARM-TD and AIM-TD parent studies, demonstrating that deutetrabenazine is well tolerated for long-term use in TD patients.
Abstract: Objective: To evaluate the long-term safety and tolerability of deutetrabenazine in patients with tardive dyskinesia (TD) at 2 years. Background: In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine showed clinically significant improvements in Abnormal Involuntary Movement Scale scores compared with placebo, and there were low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine. Design/Methods: Patients who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12 mg/day, titrating up to a maximum total daily dose of 48 mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration period and a long-term maintenance phase. Safety measures included incidence of AEs, serious AEs (SAEs), and AEs leading to withdrawal, dose reduction, or dose suspension. Exposure-adjusted incidence rates (EAIRs; incidence/patient-years) were used to compare AE frequencies for long-term treatment with those for short-term treatment (ARM-TD and AIM-TD). This analysis reports results up to 2 years (Week 106). Results: 343 patients were enrolled (111 patients received placebo in the parent study and 232 received deutetrabenazine). There were 331.4 patient-years of exposure in this analysis. Through Week 106, EAIRs of AEs were comparable to or lower than those observed with short-term deutetrabenazine and placebo, including AEs of interest (akathisia/restlessness [long-term EAIR: 0.02; short-term EAIR range: 0–0.25], anxiety [0.09; 0.13–0.21], depression [0.09; 0.04–0.13], diarrhea [0.06; 0.06–0.34], parkinsonism [0.01; 0–0.08], somnolence/sedation [0.09; 0.06–0.81], and suicidality [0.02; 0–0.13]). The frequency of SAEs (EAIR 0.15) was similar to those observed with short-term placebo (0.33) and deutetrabenazine (range 0.06–0.33) treatment. AEs leading to withdrawal (0.08), dose reduction (0.17), and dose suspension (0.06) were uncommon. Conclusions: These results confirm the safety outcomes seen in the ARM-TD and AIM-TD parent studies, demonstrating that deutetrabenazine is well tolerated for long-term use in TD patients. Study Supported by: This study was funded by Teva Pharmaceutical Industries, Petach Tikva, Israel. Disclosure: Dr. Fernandez has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Prime Education, Inc., International Parkinson and Movement Disorders Society, Carling Communications, Medscape (speaker in CME events), AbbVie, Biogen, GE Health Care, Inventiv, Kyowa Hakko Kirin, Lundbeck, Merz Pharmaceuticals, Voyager, Sunovion, Pfizer. Dr. Fernandez has received personal compensation in an editorial capacity for International Parkinson and Movement Disorders Society for serving as Medical Editor of the MDS Web Site. Dr. Fernandez has received research support from AbbVie, Acadia, Teva, Biotie/Acorda Therapeutics, Civitas, Kyowa/Prostrakan, Michael J. Fox Foundation, Movement Disorders Society, NIH/NINDS, Parkinson Study Group, Rhythm, Synosia. Dr. Stamler has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Auspex Pharmaceuticals. Dr. Davis has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Teva Pharmaceutical Industries. Dr Factor has nothing to disclose. Dr. Hauser has nothing to disclose. Dr. Jimenez-Shahed has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva, St. Jude Medical, Medtronic. Dr. Jimenez-Shahed has received research support from Avid Radiopharmaceuticals, Acadia Pharmaceuticals, St. Jude Medical, Biotie, Michael J. Fox Foundation. Dr. Ondo has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva, Lundbeck, UCB, US WorldMeds, Acadia. Dr. Ondo has received research support from dbeck, Tremor Research Group, Dystonia Coalition, Restless Leg Syndrome Foundation, Acorda. Dr. Jarskog has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche. Dr. Jarskog has received research support from Auspex/Teva, Boehringer Ingelheim, Otsuka, NIH. Dr. Woods has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Boehringer Ingelheim, Nutria Health. Dr. Woods has received research support from Teva, Pfizer. Dr. LeDoux has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Lundbeck, Acadia. Consulting: Teva Neuroscience, US WorldMeds, the Mayo Clinic, Starnes-Davis-Florie, Michael J. Fox Foundation, Benign Essential Blepharospasm Research Foundation, Dorothy/Daniel Gerwin Parkinson’s Research Fund, Auspex, Teva, Acorda, CHD. Dr. LeDoux has received personal compensation in an editorial capacity for Elsevier (for editing ‘Animal Models of Movement Disorders’ and ‘Movement Disorders: Genetics and Models’). Dr. Shprecher has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva, Lundbeck. Dr. Shprecher has received research support from Arizona Alzheimer’s Consortium, Adamas, Teva, Kyowa, MJFF, Neurocrine, NIH. Dr. Anderson has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with North American study Co-Principal Investigator for LEGATO-HD, Global Principal Investigator for AIM-TD, and Global Co-Principal Investigator for ARM-TD. Site Principal Investigator for Pride-HD, First-HD, ARC-HD: Teva. Scientific Advisor, Site Principal I.
2 citations
TL;DR: Deutetrabenazine treatment led to statistically and clinically significant improvements in TD symptoms based on the CGIC result, suggesting that clinicians were able to recognize the benefit in patients treated with deutetrABenazine.
Abstract: IntroductionTardive dyskinesia (TD) is an involuntary movement disorder that is often irreversible, can affect any body region, and can be debilitating. In the ARM-TDand AIM-TD studies, deutetrabenazine treatment demonstrated statistically and clinically significant reductions in Abnormal Involuntary Movement Scale (AIMS) scores at Week 12 compared with placebo (primary endpoint).ObjectiveTo evaluate the efficacy of deutetrabenazine, as measured by the Clinical Global Impression of Change (CGIC) scale, in patients with TD from the pooled ARM-TDand AIM-TD (24 and 36 mg/day doses) data sets, as compared with the pooled placebo cohort.MethodsARM-TD and AIM-TD were 12-week, randomized, double-blind, placebo-controlled studies that evaluated the safety and efficacy of deutetrabenazine for thetreatment of TD. The key secondary endpoint of each study was the proportion of patients “much improved” or “very much improved” (treatment success) at Week 12 on theCGIC.ResultsAt Week 12, the odds of treatment success among patients treated with deutetrabenazine (n=152) was more than double that of patients given placebo (n=107; odds ratio: 2.12; P=0.005). In a categorical analysis of CGIC ratings, patients treated with deutetrabenazine showed greater improvement than patients given placebo (P=0.003). Patients treated with deutetrabenazine also had a significantly better treatment response than those given placebo (least-squares mean CGIC score treatment difference: –0.4; P=0.006).ConclusionsDeutetrabenazine treatment led to statistically and clinically significant improvements in TD symptoms based on the CGIC result, suggesting that clinicians were able to recognize the benefit in patients treated with deutetrabenazine.Presented at: The International Congress of Parkinson’s Disease and Movement Disorders; June 4–8, 2017; Vancouver, British Columbia, Canada.Funding AcknowledgementsThese studies were funded by Teva Pharmaceutical Industries, Petach Tikva, Israel.
1 citations
TL;DR: This research presents a novel and scalable approach to treatments for Parkinson’s Disease and Movement Disorder called “informed consent” that involves real-time decision-making and individualized therapy.