Live Webcast This activity is supported by an independent - PowerPoint PPT Presentation

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

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 OSA Affects 1 in 12 • ~ 22 Million Americans have Americans 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 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 Recovery, Susceptibility Pre-symptomatic Clinical Disease Disability, Death Epigenetics Aging Genetics • • Environment Menopause • Craniofacial • • Alcohol Hypothyroidism abnormalities • • Smoking Heart failure • Ventilatory control • Sedentary lifestyle • Obesity Marin-Oto M, Vicente EE, Marin JM,. Multidisc Resp Med . 2019;14(21).

Assessment and Diagnosis History of apnea Severe snoring Post-menopausal High hip-to-waist female Suspect OSA in ratio individuals with these clinical Body habitus indicators • High BMI (≥30) or • Neck circumference ≥ 17 in for men; ≥16 in for women Male gender 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.

Other Clinical Symptoms of OSA Characteristics Also Suggestive of a Significant Risk of OSA Apnea or choking Hypertension reported by sleep partner (often treatment resistant) Atrial fibrillation Awakening with Morning headaches Daytime sleepiness choking 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 Improve Smoking Maintain sleep cessation regular hygiene sleep hours Avoid caffeine, Sleep on alcohol, and side vs. sedatives 4 to Exercise back or 6 hour before regularly stomach bedtime 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.

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 oral 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 oral appliance use improved apnea-hypopnea index (AHI), arousal index, and oxygen Mean decline in AHI 40-60% saturation, and reduced snoring • However, the benefit provided by the appliance differed substantially among trials Reduction in hourly arousals 30-50% • Patients reported high levels of adherence with the appliance • Common complaints associated with use of Decreased score on the an appliance: 23-66% Epworth sleepiness scale (ESS) • Jaw discomfort in the morning • Excessive salivation at night • Dry mouth Improvement oxygen • Teeth grinding 3-4% saturation 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.

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 Baseline Primary Endpoints Month 12 design “STAR” trial 35 32.0 • Implanted an upper airway stimulator in 28.9 30 Mean Score at 12 Months patients (n=126) with OSA resistant to CPAP 25 • 83% men 68% ↓ 70% ↓ 20 • Mean age: 54.5 years 15.3* 13.9* • Mean BMI: 28.4 15 • Primary endpoints (at Month 12) 10 • Apnea-hypopnea index (AHI) 5 • Oxygen desaturation index (ODI) 0 • Procedure-related AEs was <2% Apnea-Hypopnea Index Oxygen Desaturation Index *p<0.001 vs. baseline Strollo PJ, Soose RJ, Maurer JT, et al. N Engl J Med. 2014;370(2):139-49.

Improvements in OSA Measures Observed in the STAR Trial Were Maintained for 36 Months • 92% (116/126) of patients in the STAR 78% reduction trial completed a 36-month follow-up in sleep apnea evaluation events per hour • Improvements in objective respiratory and subjective quality-of-life outcome 76% reduction measures were maintained for 3 years in snoring post-enrollment reported by sleep partner • Adverse events were uncommon 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.

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.

Challenges In OSA Treatment • CPAP is effective, but treatment outcomes of daytime sleepiness, medical co-morbidities, such as hypertension, heart disease and diabetes are inconsistent. Up to one-third 32% of patients Half of patients who use CPAP do not of OSA patients 6+ hours consistently report excessive reported use CPAP sleepiness functional devices at 3 despite impairment. months. compliance with CPAP. 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.

A Meta-Analysis of 11 Trials Suggests the Efficacy of CPAP is Variable • Meta-analysis of 11 studies of Reduction in ESS Score with CPAP Use patients with OSA Faccenda et al, 2001 • CPAP reduced Epworth Monasterio et al, 2001 Engleman et al, 1999 Sleepiness Scale (ESS) score by a Redline et al, 1998 Ballester et al, 1999 mean of 2.94 points vs placebo Engleman et al, 1997 Jenkinson et al, 1999 • In 6 studies, which included only Barbé, 2001 patients with severe OSA and ESS Montserrat et al, 2001 Henke et al, 2001 scores >11, mean ESS reduction was Engleman et al, 1998 4.75 Combined • Mean ESS reduction in patients -2 0 2 4 6 with mild OSA was 1.1 points (NS) Change in ESS Score Patel SR, White DP, Malhotra A, Stanchina ML, Ayas NT. Arch Intern Med. 2003;163(5):565-71.