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In Integrating Novel Therapies and Recent Evidence for Obstructive Sleep Apnea into Plan Algorithms and Management Strategies

Phyllis Zee, MD, PhD Benjamin and Virginia T. Boshes Professor in Neurology Chief of Sleep Medicine Director, Center for Circadian and Sleep Medicine Northwestern University Feinberg School of Medicine

Learning Objectives

• Apply available criteria, risk factors, and clinical indicators for the

timely and accurate diagnosis of obstructive sleep apnea (OSA)

• Evaluate the efficacy and safety data associated with available and

emerging pharmacotherapies for the management of excessive daytime sleepiness (EDS) in patients with OSA

Epidemiology of Obstructive Sleep Apnea

• ~22 Million Americans have

moderate to severe OSA

• Affects ~26% of adults aged

30-70 years

• 13% of men
• 6% of women
• Only 20% with OSA have been

diagnosed OSA Affects 1 in 12 Americans

Peppard PE, Young T, Barnet JH, Palta M, Hagen EW, Hla KM. Am J Epidemiol. 2013;177(9):1006-14 Information for clinicians. SleepApnea.org website. https://www.sleepapnea.org/learn/sleep-apnea-information-clinicians/. Accessed October 2019.

Natural History of OSA

Marin-Oto M, Vicente EE, Marin JM,. Multidisc Resp Med. 2019;14(21).

Susceptibility Pre-symptomatic Clinical Disease

Genetics

• Craniofacial

abnormalities

• Ventilatory control
• Obesity

Epigenetics

• Environment
• Alcohol
• Smoking
• Sedentary lifestyle

Aging

• Menopause
• Hypothyroidism
• Heart failure

Recovery, Disability, Death

Assessment and Diagnosis

Severe snoring Male gender History of apnea Post-menopausal female High hip-to-waist ratio Body habitus

• High BMI (≥30)
• r
• Neck circumference

≥17 in for men; ≥16 in for women

Balk EM, Moorthy D, Obadan NO, et al. Diagnosis and Treatment of Obstructive Sleep Apnea in Adults [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2011 Jul. (Comparative Effectiveness Reviews, No. 32.) Available from: https://www.ncbi.nlm.nih.gov/books/NBK63560/. Accessed November 2019.

Suspect OSA in individuals with these clinical indicators

Other Clinical Symptoms of OSA

Hypertension

(often treatment resistant)

Atrial fibrillation Daytime sleepiness Awakening with choking Apnea or choking reported by sleep partner Morning headaches

Characteristics Also Suggestive of a Significant Risk of OSA

Institute for Clinical Systems Improvement. Diagnosis and treatment of obstructive sleep apnea. 6th ed. Bloomington, Minn.: Institute for Clinical Systems Improvement; June 2008.

In Interventions and OSA Treatment Modalities

Interventions: Lifestyle Modifications

Memon J, Manganaro SN. Obstructive sleep disordered breathing. StatPearls [Internet]: https://www.ncbi.nlm.nih.gov/books/NBK441909/. Updated February 21, 2019. Accessed October 2019.

Avoid caffeine, alcohol, and sedatives 4 to 6 hour before bedtime Maintain regular sleep hours Sleep on side vs. back or stomach Improve sleep hygiene Exercise regularly Smoking cessation

Interventions: Nonpharmacological Treatments

• Treat nasal obstruction
• Use of oral appliances for mild-to-

moderate OSA

• Continuous positive airway pressure

(CPAP) or bilevel positive airway pressure (BiPAP) for moderate-to-severe OSA

• Alternatives for patients who fail other

therapies

• Surgery
• Hypoglossal nerve stimulation

Memon J, Manganaro SN. Obstructive sleep disordered breathing. StatPearls [Internet]: https://www.ncbi.nlm.nih.gov/books/NBK441909/. Updated February 21, 2019. Accessed October 2019. Foldvary-Schaefer N. Sleep Apnea. Cleveland Clinic. https://my.clevelandclinic.org/ccf/media/files/Neurological-Institute/sleep-disorders-center/sleep-apnea.pdf. Accessed October 2019.

Interventions: Oral Appliances

• Patients with mild OSA who are

resistant to CPAP may benefit from an

• ral appliance
• Oral appliances are designed to

support the jaw in a forward position to help maintain an open upper airway

• Tongue-retaining mouthpieces hold

the tongue forward to keep it from collapsing into the airway

Oral appliance therapy. American Academy of Dental Sleep Medicine. https://www.aadsm.org/oral_appliance_therapy.php. Updated August 7, 2015. Accessed October 2019.

Efficacy of Oral Appliances

• Four randomized, controlled studies reported
• ral appliance use improved apnea-hypopnea

index (AHI), arousal index, and oxygen saturation, and reduced snoring

• However, the benefit provided by the

appliance differed substantially among trials

• Patients reported high levels of adherence

with the appliance

• Common complaints associated with use of

an appliance:

• Jaw discomfort in the morning
• Excessive salivation at night
• Dry mouth
• Teeth grinding

Blanco J, Zamarrón C, Abeleira pazos MT, Lamela C, Suarez quintanilla D. Sleep Breath. 2005;9(1):20-5. Mehta A, Qian J, Petocz P, Darendeliler MA, Cistulli PA. Am J Respir Crit Care Med. 2001;163(6):1457-61. Gotsopoulos H, Chen C, Qian J, Cistulli PA. Am J Respir Crit Care Med. 2002;166(5):743-8.

Mean decline in AHI Reduction in hourly arousals Decreased score on the Epworth sleepiness scale (ESS) Improvement oxygen saturation

40-60% 30-50% 23-66% 3-4%

Interventions: Hypoglossal Nerve Stimulation

• Surgically implanted device that

unilaterally stimulates the hypoglossal nerve in synchrony with ventilation

• Hypoglossal nerve stimulation

activates the genioglossus muscle, resulting in a slight forward displacement of the tongue, improving the patency of the airway

• Recommended for adults with AHI

≥15 who failed CPAP and BMI <33

The emerging option of upper airway stimulation therapy. May Clinic website. https://www.mayoclinic.org/medical-professionals/pulmonary-medicine/news/the-emerging-option-of- upper-airway-stimulation-therapy/mac-20431242. Published February 10, 2018. Accessed October 2019.

Upper Airway Stimulation Improved Measures of OSA at 12 Months

• Multicenter, prospective, single-group, cohort

design “STAR” trial

• Implanted an upper airway stimulator in

patients (n=126) with OSA resistant to CPAP

• 83% men
• Mean age: 54.5 years
• Mean BMI: 28.4
• Primary endpoints (at Month 12)
• Apnea-hypopnea index (AHI)
• Oxygen desaturation index (ODI)
• Procedure-related AEs was <2%

*p<0.001 vs. baseline Strollo PJ, Soose RJ, Maurer JT, et al. N Engl J Med. 2014;370(2):139-49.

68% ↓ 70% ↓

32.0 28.9 15.3* 13.9* 5 10 15 20 25 30 35 Apnea-Hypopnea Index Oxygen Desaturation Index Mean Score at 12 Months

Primary Endpoints

Baseline Month 12

Improvements in OSA Measures Observed in the STAR Trial Were Maintained for 36 Months

78% reduction in sleep apnea events per hour 76% reduction in snoring reported by sleep partner 81% reported nightly usage of the device

Woodson BT, Soose RJ, Gillespie MB, et al. Otolaryngol Head Neck Surg. 2016;154(1):181-8. Woodson BT, Strohl KP, Soose RJ, et al. Otolaryngol Head Neck Surg. 2018;159(1):194-202.

• 92% (116/126) of patients in the STAR

trial completed a 36-month follow-up evaluation

• Improvements in objective respiratory

and subjective quality-of-life outcome measures were maintained for 3 years post-enrollment

• Adverse events were uncommon

Interventions: Continuous Positive Airway Pressure (CPAP)

• First-line therapy for moderate to severe apnea
• CPAP involves sending a constant flow of positive

pressure into the upper airways

• Pressure is delivered through a mask or other

device that fits over the nose and/or mouth

• Constant positive pressure keeps airways open

during sleep, eliminating the obstruction that causes obstructive apnea

Redline S. JAMA. 2017;317(4):368-370.

• CPAP is effective, but treatment outcomes of daytime sleepiness,

medical co-morbidities, such as hypertension, heart disease and diabetes are inconsistent.

Weaver TE, Maislin G, Dinges DF, et al. Sleep. 2007;30(6):711-9. Antic NA, Catcheside P, Buchan C, et al. Sleep. 2011;34(1):111-9. Weaver TE, Kribbs NB, Pack AI, et al. Sleep. 1997;20(4):278-83.

32% of patients who use CPAP 6+ hours reported functional impairment. Half of patients do not consistently use CPAP devices at 3 months. Up to one-third

• f OSA patients

report excessive sleepiness despite compliance with CPAP.

Challenges In OSA Treatment

A Meta-Analysis of 11 Trials Suggests the Efficacy of CPAP is Variable

• Meta-analysis of 11 studies of

patients with OSA

• CPAP reduced Epworth

Sleepiness Scale (ESS) score by a mean of 2.94 points vs placebo

• In 6 studies, which included only

patients with severe OSA and ESS scores >11, mean ESS reduction was 4.75

• Mean ESS reduction in patients

with mild OSA was 1.1 points (NS)

Reduction in ESS Score with CPAP Use

Patel SR, White DP, Malhotra A, Stanchina ML, Ayas NT. Arch Intern Med. 2003;163(5):565-71.

Faccenda et al, 2001 Monasterio et al, 2001 Engleman et al, 1999 Redline et al, 1998 Ballester et al, 1999 Engleman et al, 1997 Jenkinson et al, 1999 Barbé, 2001 Montserrat et al, 2001 Henke et al, 2001 Engleman et al, 1998 Combined

• 2

2 4 6

Change in ESS Score

Patients with Residual Excessive Sleepiness Use CPAP Less Than Patients Without RES

Analysis of 1047 patients; n= 912 patients without residual excess sleepiness (RES-) and n=135 patients with residual excess sleepiness (RES+) as assessed by the Epworth Sleepiness Scale score *p<0.001 vs 3–4 and 4–5 h Gasa M, Tamisier R, Launois SH, et al. J Sleep Res. 2013;22(4):389-97.

18.5% 22.3% 15.0% 8.7%* 30.0% 28.6% 22.0% 12.3%* 5 10 15 20 25 30 35 3-4 h 4-5 h 5-6 h > 6 h

Prevalence of Residual Excess Sleepiness (%) CPAP Use (hours/night)

Prevalence of RES in entire cohort (n=1047) Prevalence of RES in the RES+ group (n=135)

Registry Analysis of CPAP Compliance and Residual Excessive Sleepiness (RES)

Excessive Daytime Sleepiness (EDS) in Patients with OSA Can Be Caused by Multiple Factors

In mild-to-moderate sleep apnea, daytime sleepiness may be caused by sleep disorders not impacted by use of CPAP

Periodic limb movement Chronic sleep deprivation Undiagnosed narcolepsy Idiopathic hypersomnolence

Extreme Sleepiness. National Sleep Foundation. https://www.sleepfoundation.org/articles/extreme-sleepiness. Accessed November 2019.

Interventions: Approved Therapies for Treatment of EDS in OSA

Agent Mechanism of Action Approval Date Indication Modafinil

Non-amphetamine stimulant 1998 Improve wakefulness in adults with excessive sleepiness associated with OSA

Armodafinil

R-enantiomer of modafinil; inhibits dopamine reuptake 2007 Improve wakefulness in adults with excessive sleepiness associated with OSA

Solriamfetol

Dopamine/norepinephrine reuptake inhibitor March 2019 Improve wakefulness in adults with excessive daytime sleepiness associated with OSA

PROVIGIL [modafinil package insert]. North Wales, PA: Teva Pharmaceuticals USA, Inc.; 2015; NUVIGIL [armodafinil package insert]. North Wales, PA: Teva Pharmaceuticals USA, Inc.; 2017; Sunosi [solriamfetol package insert]. Palo Alto, CA: Jazz Pharmaceuticals, Inc. 2019; Wakix [pitolisant package insert]. Plymouth Meeting, PA: Harmony Biosciences, LLC.; 2019.

Modafinil + CPAP Reduced Sleepiness in Patients with EDS More Than CPAP Use Alone

14.4 13.2 12.4 14.2 10.1* 9.6* 2 4 6 8 10 12 14 16 Baseline Week 1 Week 4

Reduction in Mean Epworth Sleepiness Scale Score

CPAP + Placebo CPAP + Modafinil

Pack AI, Black JE, Schwartz JR, Matheson JK. Am J Respir Crit Care Med. 2001;164(9):1675-81.

Epworth Sleepiness Scale Score Regular users of CPAP received modafinil (n=77) or placebo (n=80) for 4 weeks. *p<0.001 vs. CPAP + placebo

Modafinil/Armodafinil – Adverse Events

Modafinil (%) (n=934) Placebo (%) (n=567) Headache 34 23 Nausea 11 3 Nervousness 7 3 Rhinitis 7 6 Back Pain 6 5 Diarrhea 6 5 Anxiety 5 1 Dizziness 5 4 Dyspepsia 5 4 Insomnia 5 1 Armodafinil (%) (n=645) Placebo (%) (n=445) Headache 17 9 Nausea 7 3 Dizziness 5 2 Insomnia 5 1 Anxiety 4 1 Diarrhea 4 2 Dry Mouth 4 1 Depression 2 Dyspepsia 2 Fatigue 2 1

PROVIGIL [package insert]. North Wales, PA: Teva Pharmaceuticals USA, Inc.; 2015. NUVIGIL [package insert]. North Wales, PA: Teva Pharmaceuticals USA, Inc.; 2017.

Solriamfetol: A Recently Approved Therapy For EDS

• Selective dopamine and norepinephrine reuptake

inhibitor

• Distinguished from other wake-promoting agents

by its dual reuptake inhibition at dopamine and norepinephrine transporters

• Distinguished from amphetamine stimulants by

its lack of release of monoamines

• Together, these differences may account for its

wake-promoting effects and lack of rebound hypersomnia

• Low abuse potential

Baladi MG, Forster MJ, Gatch MB, et al. J Pharmacol Exp Ther. 2018;366(2):367-376. Bogan RK, Feldman N, Emsellem HA, et al. Sleep Med. 2015;16(9):1102-8. Ruoff C, Swick TJ, Doekel R, et al. Sleep. 2016;39(7):1379-87.

Differentiation of Solriamfetol from Other Wake-Promoting Agents

• Not direct- or indirect-acting dopamine receptor

agonists

• Bind to the dopamine transporter in vitro and

inhibit dopamine reuptake

• Activity associated with increased extracellular

dopamine levels in some brain regions in vivo Modafinil/Armodafinil

• Selectively inhibits reuptake of dopamine and

norepinephrine

• Reduced release of monoamines relative to

amphetamine stimulants Solriamfetol

Baladi MG, Forster MJ, Gatch MB, et al. J Pharmacol Exp Ther. 2018;366(2):367-376.

TONES 2: Effects Observed as Early as Week 1 and Maintained over 12 Weeks

*p<0.05; †p<0.001 vs. placebo 300 mg data not shown

Thorpy MJ, Shapiro C, Mayer G, et al. Ann Neurol. 2019;85(3):359-370.

Improvement in the Epworth Sleepiness Scale Score from Week 1 Through Week 12

(n=59) (n=58) (n=55)

Improvement in Objective Wakefulness from Week 1 Through Week 12

(n=59) (n=58) (n=55)

TONES 3: Maintenance of Wakefulness: Effects Observed Across the Day

*p<0.05

Schweitzer PK, Rosenberg R, Zammit GK, et al. Am J Respir Crit Care Med. 2019;199(11):1421-1431.

Solriamfetol Significantly Increased Sleep Latency

TONES 2 and TONES 3: Adverse Events

Adverse Event Placebo (n=119) Solriamfetol combined (n = 355) Any adverse event, n (%) 57 (47.9) 241 (67.9) Serious adverse event, n (%) 2 (1.7) 3 (0.8) Adverse event leading to discontinuation, n (%) 4 (3.4) 26 (7.3) Most common adverse events, n (%) Headache 10 (8.4) 36 (10.1) Nausea 7 (5.9) 28 (7.9) Decreased appetite 1 (0.8) 27 (7.6) Nasopharyngitis 8 (6.7) 18 (5.1) Dry mouth 2 (1.7) 16 (4.5) Anxiety 25 (7.0)

Schweitzer PK, Rosenberg R, Zammit GK, et al. Am J Respir Crit Care Med. 2019;199(11):1421-1431.

Summary

• CPAP is the first-line medical therapy for patients with more severe

OSA

• Excessive daytime sleepiness remains a problem for many patients

despite adequate treatment of OSA

• Modafinil and armodafinil are FDA-approved for OSA patients with

EDS

• A novel therapy, solriamfetol, has been recently approved to improve

wakefulness in adults with excessive daytime sleepiness associated with OSA

Addressing Barriers to Appropriate OSA Therapy and In Interventions for Optimal Member Access to Care

Jeffrey D. Dunn, PharmD, MBA

(Formerly)

Vice President Clinical Strategy and Programs and Industry Relations Magellan Rx Management

Learning Objectives

• Describe potential cost offsets garnered through appropriate

therapeutic interventions for OSA

• Characterize the available treatment modalities for OSA in terms of
• utcomes and patient adherence

Why is OSA So Underdiagnosed?

Atypical symptoms, particularly in women

Lack of disease awareness among physicians and patients Signature symptoms

• ccur during

sleep

Sleep Apnea: NHLBI sheds light on an underdiagnosed disorder. U.S. Department of Health and Human Services website. https://www.nhlbi.nih.gov/news/2017/sleep-apnea-nhlbi-sheds-light-underdiagnosed-disorder. Accessed October 2019. Fessenden M. Sleep Apnea in Women and Why It’s Underdiagnosed. Advanced Sleep Medicine Services, Inc. website. https://www.sleepdr.com/the-sleep-blog/sleep-apnea-in-women-and-why-its-underdiagnosed/. Accessed October 2019. Braley TJ, Dunietz GL, Chervin RD, Lisabeth LD, Skolarus LE, Burke JF. J Am Geriatr Soc. 2018;66(7):1296-1302.

Barriers to OSA Treatment

Barriers to treatment for EDS in OSA

Frost & Sullivan. Hidden health crisis costing America billions. Underdiagnosing and undertreating obstructive sleep apnea draining healthcare system. Darien, IL: American Academy of Sleep Medicine; 2016. Available at: https://aasm.org/resources/pdf/sleep-apnea-economic-crisis.pdf. Accessed October 2019.

Efficacy & safety concerns

Cost

Patient access Low awareness

Economic and Societal Burden of Undiagnosed OSA

$86.9 Billion $6.5 $26.2 $30.0 Lost Productivity Workplace Accidents Motor Vehicle Accidents Comorbid Disease

Total $149.6 Billion

Frost & Sullivan. Hidden health crisis costing America billions. Underdiagnosing and undertreating obstructive sleep apnea draining healthcare system. Darien, IL: American Academy of Sleep Medicine; 2016. Available at: https://aasm.org/resources/pdf/sleep-apnea-economic-crisis.pdf. Accessed October 2019.

Cost of Undiagnosed OSA by Member

Diagnosed, $2,105 Undiagnosed, $6,366 $0 $1,000 $2,000 $3,000 $4,000 $5,000 $6,000 $7,000 Cost per Person Diagnostic Status

Per Member Cost of OSA by Diagnostic Status

Undiagnosed Diagnosed

Plan members with undiagnosed OSA have

3x

the medical costs of those who have received a diagnosis

Frost & Sullivan. Hidden health crisis costing America billions. Underdiagnosing and undertreating obstructive sleep apnea draining healthcare system. Darien, IL: American Academy of Sleep Medicine; 2016. Available at: https://aasm.org/resources/pdf/sleep-apnea-economic-crisis.pdf. Accessed October 2019.

Importance of Diagnosis

• Reduce consequences associated with excessive

daytime sleepiness including accidents

• Mitigate long-term complications of OSA and

comorbid diseases including

• Depression
• Obesity
• Metabolic syndrome
• Type 2 diabetes
• Cardiovascular disease

Watson NF. J Clin Sleep Med. 2016; 12(8):1075-7.

OSA Treatment Options

CPAP Oral Sleep Appliances CNS Stimulants

Benefits of OSA Treatment

Benefit Notes Symptoms and daily functioning

• Improvement in sleepiness and daily functioning
• Improvement in subjective and objective sleepiness and measures of quality of life,

cognitive function, and depression Motor vehicle accidents

• Reduction in the risk of automobile accidents
• Reduction in accident frequency and concentration faults

Blood pressure, CV disease, pulmonary disease, and stroke

• Reduction in blood pressure
• CV risk reduction
• Reduced hospitalization with CV and pulmonary disease
• Reduced incidence of fatal and non-fatal CV events in patients with severe OSA
• Reduced risk of recurrent atrial fibrillation after successful cardioversion

Blood glucose

• Decrease in insulin sensitivity

Wickwire EM, Albrecht JS, Towe MM, et al. Chest. 2019;155(5):947-961. Management of obstructive sleep apnea in the primary care setting. Intermountain Health website. c. Accessed October 2019.

Both CPAP and Oral Appliances are Effective OSA Therapies

Phillips CL, Grunstein RR, Darendeliler MA, et al. Am J Respir Crit Care Med. 2013;187(8):879-87.

Apnea-Hypopnea Index (events/h)

60.0 0.0 20.0 40.0

Baseline Apnea-Hypopnea Index (events/h)

60.0 0.0 20.0 40.0

CPAP Oral Appliance

All Metrics of Sleep-Disordered Breathing Improved Regardless of Treatments

• Randomized, crossover trial comparing 1

month each of CPAP and oral appliance treatment on cardiovascular and neurobehavioral outcomes

• CPAP was more efficacious than MAD in

reducing AHI

• Sleepiness, driving simulator

performance, and disease-specific quality of life improved on both treatments by similar amounts

• Quality of life was higher with the oral

appliance vs. CPAP

(n=126 patients with moderate-severe OSA)

AHI: Apnea-Hypopnea Index MAD: Mandibular advancement device

Adherence to OSA Therapy is Key to Improving Clinical and Economic Outcomes

• Lack of adherence is a key factor

that compromises the potential benefits of treatment

• Differences in efficacy and

adherence between treatments can influence outcomes

• The potentially greater efficacy of

CPAP may be offset by inferior adherence

Phillips CL, Grunstein RR, Darendeliler MA, et al. Am J Respir Crit Care Med. 2013;187(8):879-87.

5.2 7.0* 2 4 6 8 10 CPAP Oral Appliance Patient Adherence (hours/night) p<0.00001 vs. CPAP

Adherence to the Oral Appliance was Significantly Greater vs. CPAP

(n=126 patients with moderate-severe OSA)

Concerns About the Safety of CNS Stimulants May Impact Adherence to These Agents

• The European Medicines Agency determined the benefits of modafinil-containing

medicines only outweighed their risks when treating patients with narcolepsy

• For all other indications, including EDS due to OSA, the risk for development of skin or

hypersensitivity reactions and neuropsychiatric disorders outweighed the clinical efficacy

• The US Drug Enforcement Agency has rated modafinil and armodafinil as

Schedule IV agents due to their ability to produce psychoactive and euphoric effects

• Although these agents are generally safe, concerns about their safety and/or

abuse may impact adherence leading physicians to consider newly introduced non-CNS stimulants such as solriamfetol for patients with EDS due to OSA

European Medicines Agency recommends restricting the use of modafinil. July 22, 2010. Avialable at: https://www.ema.europa.eu/en/documents/press- release/european-medicines-agency-recommends-restricting-use-modafinil_en.pdf. Accessed October 2019.

Treating OSA Saves Patients and the Health System Money

Frost & Sullivan. Hidden health crisis costing America billions. Underdiagnosing and undertreating obstructive sleep apnea draining healthcare system. Darien, IL: American Academy of Sleep Medicine; 2016. Available at: https://aasm.org/resources/pdf/sleep-apnea-economic-crisis.pdf. Accessed October 2019.

Home Workplace

• Decreased direct medical costs and

co-pays for comorbid conditions

• Hypertension
• Diabetes
• Reduced use of medication to

manage symptoms of OSA

• Alcohol
• Cigarettes
• Sleeping pills
• Reduced cost of auto accidents and

higher insurance premiums

• Fewer workplace absences per

year

• Increases productivity
• Improves employment stability
• Greater number of promotions

and bonuses

• Fewer workplace accidents

Savings Associated With OSA Treatment

• Annual savings for payers and purchasers if every American with OSA was

diagnosed and treated

• Treatment costs would be more than offset by:
• Reduced healthcare utilization
• Improved management of comorbidities
• Increased productivity
• Reduced accident-related costs

$100.1 billion

Frost & Sullivan. Hidden health crisis costing America billions. Underdiagnosing and undertreating obstructive sleep apnea draining healthcare system. Darien, IL: American Academy of Sleep Medicine; 2016. Available at: https://aasm.org/resources/pdf/sleep-apnea-economic-crisis.pdf. Accessed October 2019.

The OSA Benefit Design

Benefit Design for OSA

Formulary positioning Utilization management Benefit design

• Health plans should recognize the complexity of OSA treatment and its benefit
• Benefit design and coverage criteria should reflect recommendations of evidence-

based guidelines

• Provide inclusive coverage with reasonable cost-sharing based on formulary tiering to

avoid adversely impacting adherence to the prescribed therapeutic regimen

Sample OSA Pharmacy Benefit Design

Current guidelines advocating modafinil and armodafinil for EDS in OSA Evaluate newly introduced therapies for EDS based on safety, efficacy and cost Benefit design/coverage criteria:

• Inclusive coverage
• Promote access to agents with

different MOAs to optimize

• utcomes
• Tiering/cost-sharing
• Utilization management

Payer Case Management Services

• Examples of the benefits
• f case management

services

• Coordinate the referral

process

• Ensure patients go to the

appropriate specialists and receive best treatment

• Enhance adherence

Patient

Sleep Specialist Mental Health Professionals Social Worker Primary Care Provider Dietician, Exercise Therapist

Cardiologist, Endocrinologist, & other specialists

Summary

• A lack of disease awareness among physicians and patients leads to the

underdiagnosis of OSA

• Health plan members with undiagnosed OSA are estimated to be three times

higher than those who have received a diagnosis

• Prompt and effective treatment can mitigate the long-term complications of OSA

and minimize the impact comorbid diseases

• Lack of adherence is a key factor that compromises the potential benefits of

treatment

• Concerns about the safety of CNS stimulants may impact adherence to these

agents

• Health plans should recognize the complexity of OSA treatment and its benefit

Multidisciplinary ry Collaborations for Successful Care of Patients with OSA

Edmund Pezalla, MD, MPH Chief Executive Officer Enlightenment Bioconsult, LLC

Overview

• Review the rationale for multidisciplinary collaborations of the successful care of

patients with OSA

OSA Treatment Challenges

• Prevalence may be higher than estimated
• OSA has a multifactorial pathophysiology and is associated with increased

morbidity and mortality

• The efficacy of the current standard of care—CPAP—is limited by low adherence
• Management is often complicated by the presence of multiple comorbidities
• Access to specialized sleep laboratories and specialists is limited

Morbidity and Mortality Weekly Report. October 30, 2009. 58(42);1175-1179. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5842a2.htm. Accessed October 2019; Bartlett DJ, Marshall NS, Williams A, Grunstein RR. Sleep Med. 2008;9(8):857-64; Stepnowsky C. Med Res Archives. 2019;7(7); Peppard PE, Young T, Barnet JH, Palta M, Hagen EW, Hla KM. Am J Epidemiol. 2013;177(9):1006-14.

The Prevalence of Sleep-Related Disorders May Be Higher Than Estimated

Sleep-Related Problems Affect An Estimated 70 Million Americans1

• 1. Morbidity and Mortality Weekly Report. October 30, 2009. 58(42);1175-1179. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5842a2.htm. Accessed October 2019; 2. Bartlett DJ,

Marshall NS, Williams A, Grunstein RR. Sleep Med. 2008;9(8):857-64

Only 50% of Patients Mention Sleep Difficulties During a Primary Care Visit2

OSA is a Common, Yet Under Appreciated Chronic Sleep Disorder

• OSA has a multifactorial

pathophysiology and is associated with increased morbidity and mortality

• Highly prevalent in middle-aged to
• lder adults
• Many patients live with OSA for years

before diagnosis

• Health care costs for OSA patients are

~3x higher vs healthy controls

Stepnowsky C. Med Res Archives. 2019;7(7); Peppard PE, Young T, Barnet JH, Palta M, Hagen EW, Hla KM. Am J Epidemiol. 2013;177(9):1006-14.

Diagnosed 5% Undiagnosed 21% Unaffected 74%

Americans (30-70 y) with OSA

Guidance on the Long-Term Management of OSA is Unclear

• Clinical guidelines exist for initial treatment of

OSA with CPAP

• However guidance on long-term care is lacking
• Unanswered questions include
• Which specialist should initiate the patient’s

diagnostic and therapeutic process?

• Which specialty should be responsible for managing

comorbidities?

• How often, and for how long, should a patient be

followed after diagnosis?

• When should a new sleep study be performed?

Patil SP, Ayappa IA, Caples SM, Kimoff RJ, Patel SR, Harrod CG. J Clin Sleep Med. 2019;15(2):301-334; Patil SP, Ayappa IA, Caples SM, Kimoff RJ, Patel SR, Harrod CG. J Clin Sleep Med. 2019;15(2):335-343; Kushida CA, Nichols DA, Holmes TH, et

• al. Sleep. 2015;38(2):315-26; Marin-Oto M, Vicente EE, Marin JM,. Multidisc Resp Med. 2019;14(21).

OSA Should Be Approached as a Chronic Disease Requiring Long-Term, Multidisciplinary Care

• Rationale for multidisciplinary OSA care:
• A heterogeneous disorder with varying risk

factors, clinical presentation, pathophysiology and comorbidity

• Diagnosis and management can benefit from

a team of providers across a spectrum of specialties

• Need to manage comorbid conditions
• Increasing number of therapeutic options
• Delivery of patient-centered care

Stepnowsky C. Med Res Archives. 2019;7(7)

Features of a Multidisciplinary Sleep Center

• A multidisciplinary sleep center

provides care that is…

• Collaborative
• Coordinated
• Team-based
• Protocol-driven
• Technology-enabled
• Efficient

Traditional vs. Multidisciplinary OSA Care

Sutherland K, Kairaitis K, Yee BJ, Cistulli PA. Multidisc Respir Med. 2018;13:44.

Presentation

• Daytime

sleepiness

• Snoring
• Apnea
• Obesity

Diagnosis

• PSG
• Obtain AHI

Recognition & Diagnosis

Traditional Care Multidisciplinary Care

Risk factors Symptoms Comorbid Conditions Multi- specialty evaluation

Recognition & Diagnosis

Treatment CPAP

Treatment

Patient preference Predictors

• f

response

Adjunctive care Treatment

• f

comorbid conditions

Treatment

PSG: Polysomnography AHI: Apnea-Hypopnea Index

Monitor CPAP adherence and efficacy Reinforce CPAP Try alternative therapy Restart CPAP

Follow Up

Patient-centered outcomes Treatment optimization

Follow Up

In Multidisciplinary Management, Responsibility for Care is Shared by PCPs and Specialists

Conventional Care Multidisciplinary Care Sleep Center PCP Office PCP Office Sleep Center Intake/Screening Evaluation Diagnosis Management

Kushida CA, Nichols DA, Holmes TH, et al. Sleep. 2015;38(2):315-26

→ →

Development, implementation, and follow up of a management plan by PCP and Sleep Physician

↙ ←

Patient with sleep complaint referred to Sleep Center Patient completes sleep questionnaires

↓

Patient evaluated by a Sleep Physician and diagnostic testing ordered

↓

Diagnostic testing interpreted by a Sleep Physician

↓

Patient diagnosed by a Sleep Physician

↓

Treatment and follow up by a Sleep Physician Patient with sleep complaint referred to Sleep Center

↓

Patient screened by a PCP and nurse and referred to Sleep Center

OR

Diagnostic testing by a Sleep Technologist Patient evaluated by a Sleep Physician and diagnostic testing

• rdered as necessary

↓

Testing interpreted by a Sleep Physician

↓

Patient diagnosed by a Sleep Physician

Medical Specialties Participating in a Multidisciplinary Sleep Center

Clinical Challenge(s) Potential Specialty Involvement Refractory to CPAP

• Dentistry
• Oral and maxillofacial surgery
• Otolaryngology
• Sleep medicine

OSA and Insomnia

• Behavioral sleep medicine
• Sleep medicine

Insomnia and Post-Traumatic Stress Disorder

• Behavioral sleep medicine
• Sleep medicine
• Psychiatry

OSA and Craniofacial Anomalies

• Neurology
• Orthodontics
• Otolaryngology
• Plastic surgery
• Pulmonology
• Sleep medicine

OSA and Neuromuscular Disease

• Neurology
• Pulmonology
• Sleep medicine

Shelgikar AV, Durmer JS, Joynt KE, Olson EJ, Riney H, Valentine P. J Clin Sleep Med. 2014;10(6):693-7.

Patients Given More Therapeutic Options in a Multidisciplinary Care Setting

71% 29% No Treatment CPAP Before Multidisciplinary Evaluation After Multidisciplinary Evaluation

OSA patients (n=70) by evaluated for treatment by a multidisciplinary team that included a pulmonologist, otolaryngologist, maxillofacial surgeon and an internal medicine specialist. There was a significant reduction (p<0.001) in the number of patients given no treatment in the multidisciplinary setting vs. usual care.

Carioli D, Romano M, Colobo A, Marra M, Mantero M. Eur Respir J. 2017:3:P41.

31% 18% 12% 10% 10% 7% 4% 3% 3% Mandibular advancement device Maxillomandibular surgery Otolaryngology surgery CPAP Other Positional treatment Bariatric surgery Weight loss No treatment

Multidisciplinary Settings Allow for a More Personalized Approach to Care for Each Patient Multidisciplinary Care Setting

One or More Specific Diagnoses Specific Treatment Recommendations

Implementation of a Multidisciplinary Approach to Sleep Care

Interpretation of test results and diagnosis Discuss results with PCP to determine treatment options PCP and specialists meet with patient and caregivers to discuss treatment Evaluation by subspecialists PCP reviews physical, clinical signs and symptoms and refers to Sleep Clinic Regular monitoring and follow up by PCP

Care Team Members

• Primary care physician
• Otolaryngologist
• Oral surgeon
• Sleep medicine physician
• Orthodontist

Care Team Members (cont’d)

• Dental sleep medicine specialist
• Speech pathologist
• Nutritionist
• Bariatric surgeon

Camacho M, Ryhn MJ, Fukui CS, Bager JM. Cranio. 2017;35(2):129; Pauna HF, Serrano TLI, Moreira APSM, et al. J Otol Rhinol. 2017;6(4).

Integrating Therapy into the Multidisciplinary Care of OSA

Pauna HF, Serrano TLI, Moreira APSM, et al. J Otol Rhinol. 2017;6(4).

Assessment and routine monitoring

Primary Care

• History and physical exam
• Assessment of general health
• Management of comorbidities
• Referral to specialists
• Routine monitoring of

efficacy/safety and adherence to sleep therapy

Specialist Intervention

Sleep medicine specialist CPAP; pharmacologic therapy Dental specialist Oral appliances;

• ral surgery

Nutritionist Weight loss; healthy eating Physical Therapist Exercise; positional therapy

Case Management Services Within the Health Plan May Assist with Appropriate Referrals

• Role of case management

services

• Coordinate the referral process
• Ensures patients receive care

from the appropriate specialist(s)

Patient

Sleep Specialist Mental Health Professionals Social Worker Primary Care Provider Nutritionist, Physical Therapist Otolaryngologist, dental professionals,

• ther specialists

Summary

• OSA is underdiagnosed
• Management is complicated by the presence of multiple comorbidities
• Patients may benefit when their care is managed by a team of providers across a

spectrum of sleep medicine-related specialties

• Patients treated in a multidisciplinary setting are given access to a greater

number of therapeutic options

• Case management services can assist in the referral process to ensure patients

receive care from the appropriate specialists

Jointly provided by This activity is supported by an independent educational grant from Jazz Pharmaceuticals.

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