Treating Tardive Dyskinesia: Clinical Challenges and Patient Perspectives

Transcription

1 Treating Tardive Dyskinesia: Clinical Challenges and Patient Perspectives Interim Outcomes Report (as of November 20, 2018) Supported by an educational grant from Neurocrine Biosciences

2 Overview Activity Description: This HD video roundtable discussion includes two leading expert psychiatrists, who participate in a panel discussion of tardive dyskinesia (TD) as a widespread and undertreated condition in psychiatric populations, as well as the importance of evidence-based differential diagnostics, newly approved therapeutics for treatment of the condition, and strategies for both personalized and improved patient care. This activity also includes an interview with a leading neurologist who reviews diagnostic algorithms for TD and shares her perspective on the impact of new drug approvals and strategies for working together with psychiatrists in managing patients with TD. Throughout the activity, testimonials of a patient with tardive dyskinesia are incorporated to bring relevance to the patient perspective, experience and treatment goals. Launch Date: August 31, 2018 Expiration Date: August 31, 2019 Credit: 1.00 AMA PRA Category 1 Credit(s) TM Sponsored by: The Academy for Continued Healthcare Learning (ACHL) Supported by: An educational grant from Neurocrine Biosciences Intended Audience: This activity is intended for psychiatrists, neurologists, and other clinicians involved in the management of patients with TD. Outcomes Methodology: Activity-related changes in clinician knowledge, competence, and practices were evaluated using Level 5 outcomes to determine whether the educational objectives of the activity were achieved. Activity Availability:

3 Activity Screenshots

4 Executive Summary Participation (as of November 20, 2018) 2068 Clinical Participants; 552 Certificates (exceeds guarantee of 1500 participants!) Practicing Type Physicians, 31% Physician Assistant, 18% NP/RNs, 2% Pharmacist, 9% Other HCP Participant Satisfaction Objectivity and balance rated as good/excellent by 98% of learners Learning Objectives 99% of learners strongly agree or agree that all learning objectives were met, with an average rating of 3.43/4.0 Faculty All faculty were highly rated 3.61/4.0

5 Executive Summary (Cont d) 49% indicated participation in the activity will impact their patient outcomes. 54% of participants identified that they will change their practice by increasing evaluation of their patients for physical symptoms and/or manifestations of TD. Changes made from this activity will impact 1,389 to more than 2,711 TD patients each month. Lack of experience, lack of opportunity (patients) and reimbursement/insurance issues were reported as the most common barriers to implementing changes in practice. Following the activity, learners demonstrated increased knowledge of the causes of TD as well as the treatment efficacy of valbenazine/deutetrabenazine in their respective clinical trials.

6 Level 1: Participation Participants Certificates Participation by Specialty Participation by Clinician Type Physician Physician Assistant 2% 9% Nurse Practitioner 6% Nurse Pharmacist 12% Other HCP Family Medicine/General Practice Psychiatry Pain Medicine Internal Medicine Emergency Medicine 16% Surgery Neurology 4% Orthopedics Other 8% 6% 18% 31% 4% 5% 2% 37%

7 Level 2: Learning Objectives Please rate the following objectives to indicate if you are better able to: Evaluate possible clinical indication(s) and patient population(s) that may be at increased risk for tardive dyskinesia (TD) Discuss the role of dopamine antagonists and/or other therapies that may play a role in the pathophysiology of TD Recognize the risks, benefits, and possible complications associated with managing TD in the psychiatric population Describe the importance of differential diagnosis and current evidence-based treatment paradigms for patients at risk for TD Interpret the clinical trial efficacy and safety data of novel and emerging therapies for TD Analysis of Respondents Rating scale: 4=Strongly Agree; 1=Strongly Disagree % of learners strongly agree or agree that all learning objectives were met, with an average rating of N=542

8 Level 2: Faculty & Overall Evaluation Please rate the faculty on the criterion listed Analysis of Respondents The faculty were rated good or excellent by 99% of learners Rating scale: 4=Excellent; 1=Poor Expertise on the subject matter 3.61 Overall Evaluation Analysis of Respondents Rating scale: 4=Excellent; 1=Poor Quality of educational content 3.58 Scientific rigor 3.54 N=541

9 Level 2: Objectivity & Balance Did you perceive any bias? Rating of objectivity & balance 1% 55% 43% 99% 2% Excellent Good Fair Poor Yes No N=542 Activity was perceived as objective, balanced and non-biased.

10 Levels 3-4: Planned Frequency During a consultation, how likely are you to evaluate your patient for the physical symptoms and/or manifestations of tardive dyskinesia? If a patient is suspected of having TD, how likely are you to undertake differential diagnosis of the patient for TD? % 28% Definitely likely Pre (n=665) 38% 32% Very likely Post (n=542) 25% 19% Somewhat likely 15% 8% Not at al likely % 28% Definitely likely Pre (n=665) 41% Very likely Post (n=542) 25% 19% Somewhat likely 7% 5% Not at al likely Following the activity, 73% of learners indicated a high likelihood of evaluating patients for the physical symptoms and/or manifestations of TD vs of learners prior to the activity. Following participation in this activity, 76% of learners are highly likely to undertake a differential diagnosis of their patients for TD compared to 68% of learners prior to the activity.

11 Pretest vs. Posttest Summary Overview of Correct Responses Pre Post Topic % Change Topic 1: Recognizing Causes of TD 76% 51% 9 84% 85% 62% 95% Topic 2: Deutetrabenazine in the AIM- TD Trial 163% 32% 37% Topic 3: Valbenazine in the KINECT-3 Trial for TD 13 Topic 4: TD Patient Case for Treatment 52% Topic 1 Topic 2 Topic 3 Topic 4 Participants demonstrated improved knowledge and competence on four of four pre/posttest questions.

12 Levels 3-5: Pretest vs. Posttest vs. Follow-up Recognizing Causes of TD Pre (n=665) Post (n=550) Follow-up (n=7) 1. The following statements about the development of TD is correct EXCEPT: A. Neuroleptic-induced D2 receptor hypersensitivity in the nigrostriatal pathway is one of the suspected underlying causes B. Patients stop experiencing the pathology after dopamine antagonist therapy is terminated C. D2 receptor hypersensitivity may be at least partially due to a genetic variant D. Dopamine signaling results in the involuntary movements characteristic of the disorder % 57% 29% 24% 12% 13% 14% 4% 3% 3% Following the educational activity, there was a 76% increase in knowledge and awareness of the causes of TD, particularly that patients do not stop experiencing TD after dopamine antagonist therapy is terminated. This recognition is critical for clinicians to properly and accurately assess patients susceptible to TD and, following diagnosis, prescribe treatment. Additional educational reinforcement may be warranted in this topic as participants retention in the follow-up survey slipped 30 days post activity. For the final outcomes report, follow-up questions will solicit additional demographic data from responders in order to isolate target audience performance.

13 Pretest vs. Posttest Response by Specialty 1. The following statements about the development of TD is correct EXCEPT: Pre (n=228) Post (n=185) Pre (n=45) Post (n=37) Pre (n=391) Post (n=327) 89% 66% 84% 91% 18% 4% 8% 3% 8% 4% Psychiatrists 56% 18% 1 11% 15% 3% 3% Neurologists 42% 27% 15% 16% 3% 3% 3% Other HCPs Following the educational activity, there was a marked increase in knowledge and awareness of the causes of TD, particularly that patients do not stop experiencing TD after dopamine antagonist therapy is terminated. Psychiatrists demonstrated a 35% increase, neurologists a 5 increase and other HCPs the highest level at 117%. Such increases in recognition are critical for clinicians to properly and accurately assess patients susceptible to TD and, following diagnosis, prescribe treatment.

14 Levels 3-4: Pretest vs. Posttest Deutetrabenazine in the AIM-TD Trial Pre (n=665) Post (n=550) 2. The double-blind, randomized, phase 3, placebo-controlled AIM-TD trial evaluated the effect of 3 doses of deutetrabenazine (12 mg/day, 24 mg/day, and 36 mg/day) on the change in AIMS score from baseline to week 12. In the AIM-TD trial, which doses of deutetrabenazine were found to statistically reduce the AIMS score, compared with placebo? A. Only the 12 mg/day and 24 mg/day doses of deutetrabenazine statistically reduced the AIMS score, compared with placebo B. Only the 24 mg/day and 36 mg/day doses of deutetrabenazine statistically reduced the AIMS score, compared with placebo C. All 3 doses of deutetrabenazine statistically reduced the AIMS score, compared with placebo D. None of the doses of deutetrabenazine statistically reduced the AIMS score, compared with placebo % 39% 32% 22% 13% 7% 2% 1% Following the educational activity, knowledge and awareness of the effective doses of deutetrabenazine used in the AIM-TD clinical trial to improve patient outcomes increased by a dramatic 163% in participants. Evaluating and understanding the effective doses of deutetrabenazine is important for appropriate and effective clinical utilization of these newly approved agents.

15 Pretest vs. Posttest Response by Specialty 2. The double-blind, randomized, phase 3, placebo-controlled AIM-TD trial evaluated the effect of 3 doses of deutetrabenazine (12 mg/day, 24 mg/day, and 36 mg/day) on the change in AIMS score from baseline to week 12. In the AIM-TD trial, which doses of deutetrabenazine were found to statistically reduce the AIMS score, compared with placebo? Pre (n=228) Post (n=185) Pre (n=45) Post (n=37) Pre (n=389) 9 Post (n=327) 75% 76% 48% 28% 16% 21% 3% 8% 1% 36% 44% 16% 22% 2% 4% 26% 33% 33% 2% 7% 8% 1% Psychiatrists Neurologists Other HCPs Following the educational activity, knowledge and awareness of the effective doses of deutetrabenazine used in the AIM-TD clinical trial to improve patient outcomes increased dramaticly in participants. Psychiatrists demonstrated an impressive 168% increase, neurologists an 111% increase and other HCPs the highest level at 172%. Evaluating and understanding the effective doses of deutetrabenazine is important for appropriate and effective clinical utilization of these newly approved agents.

16 Levels 3-4: Pretest vs. Posttest Valbenazine in the KINECT-3 Trial for TD Pre (n=665) Post (n=550) 3. Recent clinical data from the phase 3 KINECT-3 trial for TD demonstrated the following: A. At week 6 in the intent-to-treat population, treatment with valbenazine at 80 mg/day resulted in a significant reduction in AIMS dyskinesia score compared with placebo B. Differences in AIMS dyskinesia score change from baseline were evident only in the 80 mg/day valbenazine treatment group, but not the 40 mg group, compared with placebo at visits on weeks 2, 4 and 6 in the intentto-treat population C. An equal percentage of participants receiving 80 mg/day valbenazine or placebo had a 5 improvement in their AIMS dyskinesia score at visits on weeks 2, 4 and 6 D. AIMS dyskinesia score improvement at week 6 in the intent-to-treat population was associated with suicidal ideation as an adverse event % 37% 3 21% 8% 5% 12% 2% Following the educational activity, learners demonstrated a dramatic increase of 13 in knowledge and awareness of the primary outcome of the KINECT-3 trial of valbenazine to reduce the AIMS dyskinesia score in trial patients. Understanding the practice-changing outcome of such a pivotal trial is crucial for widespread and effective clinical utilization of valbenazine as a newly approved agent.

17 Pretest vs. Posttest Response by Specialty 3. Recent clinical data from the phase 3 KINECT-3 trial for TD demonstrated the following: Pre (n=228) 87% Post (n=185) Pre (n=45) 87% Post (n=37) Pre (n=391) 84% Post (n=327) 43% 29% 5% 7% 8% 1% 44% 27% 18% 8% 11% 5% 36% 3 22% 1 12% 4% 2% Psychiatrists Neurologists Other HCPs Following the educational activity, learners demonstrated great increases in knowledge and awareness of the primary outcome of the KINECT-3 trial of valbenazine to reduce the AIMS dyskinesia score in trial patients. Psychiatrists demonstrated a 102% increase, neurologists the highest at a 202% increase and other HCPs at 133%. Understanding the practice-changing outcome of such a pivotal trial is crucial for widespread and effective clinical utilization of valbenazine as a newly approved agent.

18 Levels 3-4: Pretest vs. Posttest TD Patient Case for Treatment Pre (n=665) Post (n=550) 4. A 45-year-old male with a diagnosis of schizophrenia and stable psychiatric status has had dopamine receptor blocker induced tardive dyskinesia for 5 years. The treatment with the best combination of effectiveness and tolerability for treating persistent TD in this patient case is: A. Vitamin E B. Valbenazine or deutetrabenazine C. Omega-3 fatty acids D. Amantadine Understanding and the ability to evaluate a TD patient case for treatment suitability with valbenazine or deutetrabenazine increased by 53% following the educational activity. Given the new approvals of these agents, such clinical cases, and reinforced education surrounding them, are crucial for clinicians to identify, diagnose and select patients who would benefit from prescribing these new therapies and to utilize them accordingly % 62% 14% 1 14% 2% 2% 1%

19 Pretest vs. Posttest Response by Specialty 4. A 45-year-old male with a diagnosis of schizophrenia and stable psychiatric status has had dopamine receptor blocker induced tardive dyskinesia for 5 years. The treatment with the best combination of effectiveness and tolerability for treating persistent TD in this patient case is: Pre (n=228) Post (n=185) 98% 83% Pre (n=45) Post (n=37) 97% 78% Pre (n=391) Post (n=327) 94% 48% 9% 4% 1% 4% 1% 11% 4% 7% 3% 14% 18% 1% 3% 2% Psychiatrists Neurologists Other HCPs Understanding and the ability to evaluate a TD patient case for treatment suitability with valbenazine or deutetrabenazine increased modestly among psychiatrists and neurologists, yet robustly among general HCPs following the educational activity. Psychiatrists demonstrated an 18% increase, neurologists a 24% increase and other HCPs the highest level at 96%. Given the new approvals of these agents, such clinical cases and reinforced education surrounding them are crucial for clinicians to identify, diagnose and select patients who would benefit from prescribing these new therapies and to utilize them accordingly.

20 Activity Impact Self-reported activity impact Yes No No change Increase knowledge 65% 32% 3% Increase competence 54% 41% 5% Improve performance 51% 42% 7% Improve patient outcomes 49% 44% 7% 49% of attendees indicated participation in this activity will improve their patients outcomes. N=542; see comments on next slide

21 Activity Impact Self-reported increase in knowledge Able to recognize and understand tardive dyskinesia better Able to update my knowledge on newer evidence based pharmacological interventions for management of TD Awareness of newly available treatment options Better understanding of mechanisms of action Did not know what TD was, risk factors or treatment options as well as patient impact on QOL Extended knowledge in medical efforts Helped me know more about the two recently approved drugs Helped place in perspective differing treatments I am better to understand some of the affects related to TD when compared to psychiatric population and medication I have a better understanding of recognizing TD, risk factors and treatment with new agents Understanding of new class of medications that block packaging of neurotransmitter dopamine in the presynaptic nerve terminal The effective dosages of valbenazine and deutetrabenazine Learned more about 2 new agents and some off-label treatments I had no idea of the emerging treatments Although not a significant part of my practice, i find it incredibly interesting to learn Always great to learn about available medications Better at recognizing TD Collaborative team afford for better outcome for pts Did not know about new FDA approved meds (do not treat many schizophrenic pts) Familiarity with medications to treat TD is greater Gave evidence based information for future use of these meds Good review and extra knowledge I am a nurse so it help me understand and provide proper care and education to the patient I believe that after this activity I am better equipped to recognize, evaluate and treat patients who may unfortunately develop TD This was clinical information of which I was not associated. The entire CME was beneficial Provided information on recent results of clinical trials for the two new TD treatments It emphasizes affective disorders as higher risk for development of TD. I will start using TD med more readily

22 Activity Impact (Cont d) Self-reported increase in competence Aid in choosing alternative therapy for psychiatric treatment Awareness of treatment/evidence based outcomes Better able to assess diff movement disorders Better able to differentiate between TD and other conditions. Learned limitations of AIMS score Reinforced my practice of collaborating with neurologists and primary care providers to promote more effective outcomes I now have confidence in using these two new medications for my patients with tardive dyskinesia I now know to consider valibenazine or deutetrabenazine in patients who have tardive dyskinesia More competent in using antipsychotic meds in kids i see and in responding to td when it occurs Self-reported increase in performance Able to provider better patient education Be familiar with the ses and tx Better able to differentiate between moments of TD verses other movement disorders. Reinforced my practice of assessing TD in patients with history of dopamine receptor blocking agents and the need to add TD as a diagnosis requiring assessment during each clinic visit Help me be aware of TD in psychiatric patients I can possibly help patients with TD better than I used to be able to I feel better equipped to treat patients showing signs of TD, though it still makes me nervous when patients develop this unwanted SE Will screen the patient more carefully More likely to prescribe vmats Allow me to advocate for addition to our formulary Became aware of factors which increase the probability that a patient on dopamine blockers will develop TD Gave me more options to treat TD I can apply this to my clinical practice/pts. Via improved assessment and availability of drugs for TD I have a better understanding of recognizing TD, risk factors and treatment with new agents Importance of doing AIMS reassessment at intervals Increased confidence in using approved med's for TD More confident in the use of diagnostic criteria for tardive dyskinesia Will consider TD more profoundly in patients with abnormal movements; improve patient education prior to treatment Being aware of long term effects of dopamine antagonists if TD manifests Better awareness, earlier diagnosis Better understanding of new FDA drugs and efficacy shown through scientific trials. Concentrate on monitoring for emergent symptoms I am now more intuitive about the etiology and current treatment of TD I will be better to diagnose tardive dyskinesia and use the AIMS test to rate severity Proper combination of lowering the offending drug and adding a medicine to reduce TD Recognition of TD as separate from other movement disorders Screening and implementing appropriate measures

23 Activity Impact (Cont d) Self-reported increase in patient outcomes Anticipate higher level of satisfying outcome for pts Better symptoms control and functionality for pts Because I have been undermanaging this condition Better control of involuntary movements Earlier diagnosis, more effective treatment I currently have a patient with tardive dyskinesia that I plan to start on one of these medications I hope so- more awareness and treatment options are helpful I know the treatment and what dosing decreases sx Improved treatment for patients Reinforced my practice of the necessity to collaborate with other specialists a promote the best outcome for the TD patient More confidence use antipsychotics and manage td Patients will be more likely to remain on an antipsychotic that is benefiting them, now that the severity of TD can be greatly reduced This activity might improve my patient outcomes if I have patients with TD who respond well to valibenazine and deutetrabenazine Will be more sensitive to need for earlier DX and TX Appropriate referrals Better effectiveness and side effect burden Diagnosing TD and early management I commonly treat patient's with dopamine antagonists; therefore, my patients more susceptible to TD. I have a better understanding of recognizing TD, risk factors and treatment with new agents I will be more focused on recognizing even subtle TD and most important steps to take to reduce same or use the two new medications Increased my ability to diagnose TD and differentiate among other movement disorders Increased my understanding of recent clinical trials showing efficacy of the two new FDA approved therapies. Increased my knowledge about risk factors associated with TD, other than hx of dopamine receptor blocking agents. Validated my understanding of the limitations of the AIMS test for diagnostic purposes When I encounter patients on psychotropic meds, I will be more aware what to look for

24 Practice Change: Planned vs. Actual Since completing the activity, in what ways do you plan to change (or have changed) the management of your patients with tardive dyskinesia (TD)? Select all that apply Increase evaluation of my patients for the physical symptoms and/or manifestations of TD 54% 71% Increase referral of my patients suspected of having TD to a movement disorder specialist Greater utilization of FDA approved agents such as valbenazine and deutetrabenazine for treatment of patients with TD 32% 29% 37% Post (n=542) Follow-up (n=7) Other changes This activity validated my current practice; no changes will be made 4% 14% 17% 14% % of learners planned to change their practice immediately following the activity; in measuring the extent to which they implement through a follow-up survey of participants, 86% of respondents reported having changed their practice! Multiple responses allowed; see comments on next slide

25 Planned Practice Changes Self-attested changes to practice as a result of participating in this activity: Try to get approval for tx agents helpful for TD Identify suspicion of TD more consistently Initiate tx more readily Be more aware of TD symptoms Refer these patients to, or obtain in-hospital consultation of a specialist Attempt to get payment for meds More aware of new treatment available for TD Think of other differential diagnosis of TD Advice if seen implementing practical changes Aims testing more frequently. Re evaluate antipsychotics for MDD Assess medication list and neurological diseases Awareness of TD and prescribing options Be able to diagnose TD and refer to appropriate specialty Be more aware of meds that cause TD and observation of patients Better screen of movement disorder. Be on guard for TD on patients taking antipsychotics Careful evaluation plus neurological consulting Closer evaluation using AIMS Consider collaboration with neurologist Educate patient regarding new treatment option for TD Consider using these 2 drugs as opposed to amantadine or vitamin E Discuss with patients the risks and benefits of the newer medications for TD Spend more time on evaluation of abnormal movements to determine if they are due to tardive dyskinesia Inform patient of new treatment options if appropriate More closely watch for signs of TD in patients on dopamine receptor blockers Probably make early referrals to TD specialists Evaluation of tardive dyskinesia If positively td, then refer to the movement disorder specialist. Evaluate td 2. Differential diagnosis of TD Consider TD as a differential diagnosis. Be more vigilant evaluating movement disorders. Increase evaluation of my patients for TD Consider use of valibenazine and deutetrabenazine for patients with TD Consider the new FDA meds Promote this to colleagues Assess for TD and perform differential diagnosis Avoid excessive imaging studies, keep patients informed Be more alert to T.D. Symptoms. Be more aggressive in treating T.D. Spend more time in evaluating the condition and referring to correct help Implement usage of more medications with these potential because before I did not use these medications because of the hesitancy of creating TD. Now I have a better understanding of TD and what can be done if a patient develops this symptom Consider other movement disorders, prescribe these medicines Consider prescribing the two new drugs if covered by insurance Consider requesting from our pharmacy these TD approved medications - will require a non-formulary request Seek resources for patients who may not be able to afford the newer treatments Lower my threshold to prescribing the FDA approved agents for TD More complete history and physical exam to better make a recommendation for referral Perform AIMS test regularly, discuss benefit/risks of antipsychotic meds

26 Patient Care Impact Number of patients affected by these changes each month: >10 46% 11% 2% 2% 39% Changes will impact 1,389 to more than 2,711 TD patients each month. This assumes data in chart above is representative of all healthcare professionals that participated (2068), who indicated they have changed their practice as a result of their participation in this activity (86%). N=542

27 Barriers to Planned Change Cost Patient compliance issues 15% 16% Lack of time to assess/counsel patients 1 Lack of opportunity (patients) Lack of experience 23% 24% Reimbursement/insurance issues 18% Lack of administrative support 12% Lack of consensus or professional guidelines 4% Lack of resources (equipment) 8% Other 3% No barriers 18% 5% 1 15% 25% 3 Participants indicated lack of experience (24%) as most common barrier to implementing changes in their practice, followed by lack of opportunity (23%) and reimbursement/insurance issues (18%). Of those who identified barriers, 79% will attempt to address the perceived barrier(s) in order to affect change. N=542; multiple responses allowed

28 Level 5: Follow-up Survey Confidence How confident are you in utilizing an FDA approved agent such as valbenazine or deutetrabenazine for treatment of your patients with TD? Very confident 15% Follow-up Survey Moderately confident 57% Somewhat confident 14% Not at all confident 14% % of participants responded they were confident or very confident in using valbenazine or deutetrabenazine for treatment of TD patients. Future education that supports and enhances individualized education and reinforced real-world clinical applications would prove essential for maximal utilization in affected patients. N=7

29 Contact Information Richard Keenan VP, Education Development Academy for Continued Healthcare Learning (ACHL) E: P: ext. 215 C: