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Eva: Long-term Treatment of TD With AUSTEDO XR

Photo of “Eva,” looking straight into camera, hair pulled back

Eva, 52 Years

Eva, 52, is a divorced real estate agent

Medical History

  • MDD with poor response to monotherapy

Medication History

  • Selective serotonin reuptake inhibitors (5 years)
  • Atypical antipsychotic drug (4 years)

Current Presentation

  • Involuntary mouth movements when talking to clients, affecting her work

Assessment

  • Performed Abnormal Involuntary Movement Scale (AIMS) exam

Not an actual patient. Image is for illustrative purposes only.

Eva’s AIMS Exam Confirms TD

MOVEMENT RATINGS SCORE
Facial & Oral
Movements		 1.

Muscles of facial expression

 01234
2.

Lips and perioral area

 01234
3.

Jaw

 01234
4.

Tongue

 01234
Extremity
Movements		 5.

Upper (arms, wrists, hands, fingers)

 01234
6.

Lower (legs, knees, ankles, toes)

 01234
Trunk Movements 7.

Neck, shoulders, hips

 01234
Global Judgments 8.

Severity of abnormal movements overall

 01234
9.

Incapacitation due to abnormal movements

 01234
10.

Patient awareness of abnormal movements

 01234
Dental Status 11.

Current problems with teeth/dentures?

 NOYES
12.

Are dentures usually worn?

 NOYES
Total AIMS Score = 10

Diagnosis

  • TD, based on visual assessment with the AIMS and Diagnostic and Statistical Manual of Mental Disorders, 5th ed, Text Revision criteria

Clinical Decision

  • Consider the impact of symptoms on her career
  • VMAT2 inhibitors are recommended for TD that has an impact on the patient
  • Treat with once-daily AUSTEDO XR

Treatment With AUSTEDO® Resulted in Statistically Significant TD Symptom Control in the AIM-TD Trial

In the Addressing Involuntary Movements in Tardive Dyskinesia (AIM-TD) trial

  • Placebo: 1.4-point reduction vs baseline
  • 36 mg/day: 3.3-point reduction vs baseline
  • −1.9-point treatment effect vs placebo (P=0.001)


Patients in the AIM-TD clinical trial received the AUSTEDO BID formulation.

In the AIM-TD study, a 12-week, placebo-controlled, fixed-dose trial, adults with TD, ages 21 to 81 years, were randomized 1:1:1:1 to 12 mg of AUSTEDO, 24 mg of AUSTEDO, 36 mg of AUSTEDO, or placebo. The dose of AUSTEDO was started at 12 mg/day and increased at weekly intervals in 6-mg/day increments to a dose target of 12 mg/day, 24 mg/day, or 36 mg/day. The primary efficacy endpoint was change from baseline to Week 12 in AIMS total score in the 36-mg/day group vs placebo, assessed by blinded central video rating.

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  • In the phase 3 trials for AUSTEDO, the most common adverse events (AEs) were nasopharyngitis and insomnia
  • Of patients taking AUSTEDO:
  • Discontinuation due to AEs occurred in 4% of patients vs 3% of patients on placebo
  • Dose reduction due to AEs was required in 4% of patients vs 2% of patients taking placebo
  • Adverse reactions with AUSTEDO XR are expected to be similar to AUSTEDO BID

The RIM-TD Trial Showed Rapid TD Symptom Control* With Sustained Results Across ~3 Years

Analysis of the Open-Label Rollover Study of Patients From ARM-TD and AIM-TD: Change in AIMS Total Score From Baseline

A purple graph showing the RIM-TD 3-year downward trend of AIMS scores in patients taking AUSTEDO, overlayed by blue dotted lines representing years

Patients in the Reducing Involuntary Movements in Participants With Tardive Dyskinesia (RIM-TD) study received the AUSTEDO BID formulation.


*Symptom control defined as change in total AIMS score observed as early as Week 2 in placebo-controlled studies.

†Mean total daily dose.

Additional Long-term Results

  • 67% of patients had a ≥50% improvement in AIMS score through year 3
  • A majority of patients and physicians reported symptoms as “much improved” or “very much improved” at Week 145 (Patient Global Impression of Change [PGIC] of 63% and Clinical Global Impression of Change [CGIC] of 73%)
  • TD symptom improvement achieved while psychiatric scale scores generally remained stable
  • AEs in the 3-year study were comparable to those in the 12-week clinical trials
  • Mean overall adherence rate was ~90% at 3 years*

Patients in the RIM-TD study received the AUSTEDO BID formulation.


*Overall compliance based on pill counts.

Most Patients in Aim to Reduce Movements in Tardive Dyskinesia (ARM-TD) and RIM-TD Received Doses ≥30 mg/day

Dose Distribution in ARM-TD at Week 5

Bar chart showing dose distribution at Week 5 in ARM-TD

Dose Distribution in RIM-TD at Week 6

Bar chart showing dose distribution at Week 6 in RIM-TD

Patients in the ARM-TD and RIM-TD studies received the AUSTEDO BID formulation.

Flexibility for Effective and Tolerable Control

Flexibility to titrate weekly until effective and tolerable symptom control is reached (48 mg maximum dose)

Graphic showing pictures of the single-dose tablets for every titration of AUSTEDO XR

Additional dosing and administration information:

  • Once-daily AUSTEDO XR may be taken with or without food
  • AUSTEDO XR should be swallowed whole. Tablets should not be chewed, crushed, or broken
  • The maximum recommended daily dose of AUSTEDO XR is 48 mg/day

Most patients were taking between 36 mg/day and 48 mg/day at the end of the long-term study (RIM-TD)*

Icon of blue clipboard with lines on it overlayed by magnifying glass shape, the circle filled with a 5-point star, all against a white background in a blue circle

Patients in the RIM-TD study received the AUSTEDO BID formulation.


*Overall compliance based on pill counts.

Getting Patients Started With the Titration Kit

4-week Titration Kit available through sample and prescription*

of 4-week Patient Titration Kit showing dosing on Weeks 5, 6, and 7

Eligible patients can start at no cost with the 4-week Titration Kit. Exclusions and limitations apply. See details at AUSTEDOCARDFORM.COM.

Image shown is not the actual 4-week Titration Kit. Tablets not shown to actual size.


In the real-world START study of the 4-week Titration Kit†,‡:

  • 90% of the patients adhered to the Titration Kit
  • A majority of patients reached ≥24 mg/day by Week 4
  • Patients and physicians reported:
  • Treatment success consistent with pivotal studies
  • Easy-to-follow titration schedule
  • Overall satisfaction with the Titration Kit

*Prescription should not include refills; provide a separate prescription for maintenance dose.

†The START study was a noninterventional, real-world study assessing 4-week Titration Kit utilization and treatment success in 53 patients with TD and 17 patients with Huntington’s disease chorea, both of similar demographics to the AUSTEDO pivotal studies. ‡Based on PGIC and CGIC.

Case Study: Initiation and Titration

Photo of Eva looking straight into camera, simple background, chain necklace, gray shirt, hair loose at sides of head

Eva

Getting Started on AUSTEDO XR

  • Received a 4-week sample Titration Kit of AUSTEDO XR
  • Received a prescription for 36 mg AUSTEDO XR once daily to use after completion of the sample pack
  • Eva’s provider set expectations regarding treatment over the titration period and the importance of staying on therapy
  • Her provider asked her to call the office in 2 weeks to check in
Eva dose and AIMS score at week 0.
Photo of Eva looking straight into camera, simple background, chain necklace, gray shirt, hair loose at sides of head

Eva

Follow-up Appointment at 4 Weeks

  • After 2 weeks, Eva called the office and reported that she had noticeable improvements in her symptoms
  • At her visit, her AIMS score was reduced to a 7
  • Eva was instructed to finish the 4-week sample Titration Kit and then to begin the prescription for her maintenance dose of 36 mg once daily
  • Eva scheduled a follow-up visit in 4 weeks
Eva dose and AIMS score at week 4.
Photo of Eva looking straight into camera, simple background, chain necklace, gray shirt, hair loose at sides of head

Eva

Follow-up Appointment at 8 Weeks

  • Eva is currently taking 36 mg of AUSTEDO XR once daily
  • Her AIMS score has been reduced to a 6
  • She is happy with her TD symptom control and would like to remain on the current dose
Eva dose and AIMS score at week 8.
Photo of Eva looking straight into camera, simple background, chain necklace, gray shirt, hair loose at sides of head

Eva

Follow-up After 6 Months on AUSTEDO XR

  • 6 months after starting once-daily AUSTEDO XR, Eva’s symptoms, while still present, have improved
  • Eva is now comfortable and familiar with once-daily AUSTEDO XR
  • Together, she and her provider discuss whether to increase her dose to see if her TD symptoms can be reduced further
  • Her provider writes a prescription for 42 mg once daily
  • 4 weeks later, Eva feels her symptoms have improved, and she wants to continue with the increased dose of 42 mg/day
Eva dose and AIMS score at week 26.
Photo of Eva looking straight into camera, simple background, chain necklace, gray shirt, hair loose at sides of head

Eva

Treatment With AUSTEDO XR up to ~3 Years

  • 2 years after starting AUSTEDO XR, Eva’s symptoms have continued to improve, enabling her to speak to her clients with less difficulty
  • With her TD improved, she and her clinician are more focused on the management of her MDD
  • Eva continues to regularly see her psychiatry provider for management of her MDD and to monitor her TD treatment with AUSTEDO XR
  • At 3 years after starting AUSTEDO XR, Eva’s symptoms have continued to improve, her MDD is stable, and she continues to take her antipsychotic medication
Eva dose and AIMS score at year 3.

Not an actual patient. Image is for illustrative purposes only.

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Thank you for completing

Case Studies: Chapter 4 — Dosing and Long-term Treatment

Patient Case: Eva

Orange clipboard with checkmarks next to 3 lines, surrounded by an orange circle.

Summary:

Like Eva, patients taking AUSTEDO XR for long-term treatment of their TD symptoms can expect to see sustained results. In the open-label extension study with the AUSTEDO twice-daily formulation, sustained results were observed through ~3 years and AEs were comparable to those observed in the pivotal 12-week controlled clinical trials.

Chapter 4 References:

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed, Text Revision. Washington, DC: American Psychiatric Association; 2022.

American Psychiatric Association. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia. 3rd ed. Washington, DC:

American Psychiatric Association; 2021.

Anderson KE et al. Lancet Psychiatry. 2017;4(8):595-604.

AUSTEDO XR® (deutetrabenazine) extended-release tablets/AUSTEDO® current Prescribing Information. Parsippany, NJ: Teva Neuroscience, Inc.

Data on file. Teva Neuroscience, Inc. Parsippany, NJ.

Guy W. ECDEU Assessment Manual for Psychopharmacology: Revised. Rockville, MD; 1976:534-537.

Hauser RA et al. Front Neurol. 2022;13:773999.

INDICATIONS AND USAGE

AUSTEDO XR® (deutetrabenazine) extended-release tablets and AUSTEDO® (deutetrabenazine) tablets are indicated in adults for the treatment of chorea associated with Huntington’s disease and for the treatment of tardive dyskinesia.

IMPORTANT SAFETY INFORMATION

Depression and Suicidality in Patients with Huntington’s Disease: AUSTEDO XR® and AUSTEDO® can increase the risk of depression and suicidal thoughts and behavior (suicidality) in patients with Huntington’s disease. Balance the risks of depression and suicidality with the clinical need for treatment of chorea. Closely monitor patients for the emergence or worsening of depression, suicidality, or unusual changes in behavior. Inform patients, their caregivers, and families of the risk of depression and suicidality and instruct them to report behaviors of concern promptly to the treating physician. Exercise caution when treating patients with a history of depression or prior suicide attempts or ideation. AUSTEDO XR and AUSTEDO are contraindicated in patients who are suicidal, and in patients with untreated or inadequately treated depression.

Contraindications: AUSTEDO XR and AUSTEDO are contraindicated in patients with Huntington’s disease who are suicidal, or have untreated or inadequately treated depression. AUSTEDO XR and AUSTEDO are also contraindicated in: patients with hepatic impairment; patients taking reserpine or within 20 days of discontinuing reserpine; patients taking monoamine oxidase inhibitors (MAOIs), or within 14 days of discontinuing MAOI therapy; and patients taking tetrabenazine or valbenazine.

Clinical Worsening and Adverse Events in Patients with Huntington’s Disease: AUSTEDO XR and AUSTEDO may cause a worsening in mood, cognition, rigidity, and functional capacity. Prescribers should periodically re-evaluate the need for AUSTEDO XR or AUSTEDO in their patients by assessing the effect on chorea and possible adverse effects.

QTc Prolongation: AUSTEDO XR and AUSTEDO may prolong the QT interval, but the degree of QT prolongation is not clinically significant when AUSTEDO XR or AUSTEDO is administered within the recommended dosage range. AUSTEDO XR and AUSTEDO should be avoided in patients with congenital long QT syndrome and in patients with a history of cardiac arrhythmias.

Neuroleptic Malignant Syndrome (NMS), a potentially fatal symptom complex reported in association with drugs that reduce dopaminergic transmission, has been observed in patients receiving tetrabenazine. The risk may be increased by concomitant use of dopamine antagonists or antipsychotics. The management of NMS should include immediate discontinuation of AUSTEDO XR and AUSTEDO; intensive symptomatic treatment and medical monitoring; and treatment of any concomitant serious medical problems.

Akathisia, Agitation, and Restlessness: AUSTEDO XR and AUSTEDO may increase the risk of akathisia, agitation, and restlessness. The risk of akathisia may be increased by concomitant use of dopamine antagonists or antipsychotics. If a patient develops akathisia, the AUSTEDO XR or AUSTEDO dose should be reduced; some patients may require discontinuation of therapy.

Parkinsonism: AUSTEDO XR and AUSTEDO may cause parkinsonism in patients with Huntington’s disease or tardive dyskinesia. Parkinsonism has also been observed with other VMAT2 inhibitors. The risk of parkinsonism may be increased by concomitant use of dopamine antagonists or antipsychotics. If a patient develops parkinsonism, the AUSTEDO XR or AUSTEDO dose should be reduced; some patients may require discontinuation of therapy.

Sedation and Somnolence: Sedation is a common dose-limiting adverse reaction of AUSTEDO XR and AUSTEDO. Patients should not perform activities requiring mental alertness, such as operating a motor vehicle or hazardous machinery, until they are on a maintenance dose of AUSTEDO XR or AUSTEDO and know how the drug affects them. Concomitant use of alcohol or other sedating drugs may have additive effects and worsen sedation and somnolence.

Hyperprolactinemia: Tetrabenazine elevates serum prolactin concentrations in humans. If there is a clinical suspicion of symptomatic hyperprolactinemia, appropriate laboratory testing should be done and consideration should be given to discontinuation of AUSTEDO XR and AUSTEDO.

Binding to Melanin-Containing Tissues: Deutetrabenazine or its metabolites bind to melanin-containing tissues and could accumulate in these tissues over time. Prescribers should be aware of the possibility of long-term ophthalmologic effects.

Common Adverse Reactions: The most common adverse reactions for AUSTEDO (>8% and greater than placebo) in a controlled clinical study in patients with Huntington’s disease were somnolence, diarrhea, dry mouth, and fatigue. The most common adverse reactions for AUSTEDO (4% and greater than placebo) in controlled clinical studies in patients with tardive dyskinesia were nasopharyngitis and insomnia. Adverse reactions with AUSTEDO XR extended-release tablets are expected to be similar to AUSTEDO tablets.

Please see accompanying full Prescribing Information, including Boxed Warning.