Management of GERD beyond PPIs Qing Zhang, MD PhD Gastroenterology, Virginia Mason Medical Center

Epidemiology - 16 studies of GERD epidemiology • Range of GERD prevalence estimates was 18.1%–27.8% in North America (comparing to 10-20% in 2005 publication) 8.8%–25.9% in Europe 2.5%–7.8% in East Asia (Comparing to 4.5s • Distal contractile index (DCI) 430-5000 mmHgcm-s • Coordinated vigorous contraction increases intrabolus driving pressure

UES relaxation pressure

Distal contractile integral (DCI) (mmHg-s-cm)

Delayed Latency

LES relaxation pressure

HRM: From Motility To Function • Peristalsis contraction and coordination defines whether motor activity is normal • Intra-bolus pressure and pressure gradient define whether motility drives effective function • Concurrent impedance confirms bolus transport

Ambulatory pH monitoring • Wireless – Bravo pH study - Better tolerance, but chest pain common - Allow 48-96hr recording. Prolonged recording can evaluate off/on PPI in a single test. - Unable to assess non-acid reflux

• Catheter based – 24hr single pH, dual pH, pH/impedance - Better designed catheters increase tolerance - Intragastric pH monitoring allow to assess effectiveness of PPI/H2RA - Impedance recording to assess non-acid reflux and swallowing - Impedance recording to exclude “acid reflux event” due to drinking acidic fluid

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Wireless Bravo pH monitoring

Abnormal Bravo pH testing: - 85 episodes of acid reflux

- 6.9% fraction time of pH strain induced reflux events

Mechanisms of GERD – Acid pocket • An area of unbuffered gastric acid that accumulates in the proximal stomach after meals and serves as the reservoir for acid reflux in healthy individuals and gastroesophageal reflux disease (GERD) patients • There are differentiating features between these populations in the size and position of the acid pocket, with GERD patients predisposed to upward migration of the proximal margin onto the esophageal mucosa, particularly when supine. • Alginate / antacid combination (Gaviscon) Kahrilas PJ, et all. The Acid Pocket: A Target for Treatment in Refl ux Disease ? Am J Gastroenterol 2013; 108:1058–1064

Mechanisms of GERD – Ineffective esophageal motility • Poor esophageal contraction affect esophageal clearance, therefore, prolong acid exposure time.

Mechanisms of GERD – Bile reflux • Difficult to distinguish from acid reflux. • Possible contributing factor of refractory GERD • Can be detected by 24hr Bilitec bile reflux testing system. • Bile binding agent, IW 3718, is in phase IIa trial

GERD – Typical Symptoms • Regurgitation – Nocturnal regurgitation associated with higher incidence of Barrett esophagus • Heartburn • Non-cardiac chest pain • Dysphagia

GERD – Atypical Symptoms • Cough • Sore throat/ENT symptoms • Asthma

GERD Treatment – Life style change • Weight loss is recommended for GERD patients who are overweight or have had recent weight gain. • Head of bed elevation and avoidance of meals 2 – 3 h before bedtime should be recommended for patients with nocturnal GERD. • Routine global elimination of food that can trigger reflux (including chocolate, caffeine, alcohol, acidic and / or spicy foods) is not recommended in the treatment of GERD.

Philip O. Katz, et al. Guidelines for the Diagnosis and Management of Gastroesophageal Refl ux Disease. Am J Gastroenterol 2013; 108:308 – 328

GERD Treatment – PPIs • There are no major differences in efficacy between the different PPIs. • PPI therapy should be initiated at once a day dosing, before the first meal of the day. • Non-responders to PPI should be referred for evaluation. • In patients with partial response to PPI therapy, increasing the dose to twice daily therapy or switching to a different PPI may provide additional symptom relief. • Maintenance PPI therapy should be administered for GERD patients who continue to have symptoms after PPI is discontinued, and in patients with complications including erosive esophagitis and Barrett’s esophagus. Philip O. Katz, et al. Guidelines for the Diagnosis and Management of Gastroesophageal Refl ux Disease. Am J Gastroenterol 2013; 108:308 – 328

Risks of PPI use • PPIs are safe in pregnant patients if clinically indicated. • Patients with known osteoporosis can remain on PPI therapy. Concern for hip fractures and osteoporosis should not affect the decision to use PPI long-term except inpatients with other risk factors for hip fracture. • PPI therapy can be a risk factor for Clostridium diffi cile infection, and should be used with care in patients at risk. • Short-term PPI usage may increase the risk of community-acquired pneumonia. The risk does not appear elevated in long-term users. • PPI therapy does not need to be altered in concomitant clopidogrel users as there does not appear to be an increased risk for adverse cardiovascular events. Philip O. Katz, et al. Guidelines for the Diagnosis and Management of Gastroesophageal Refl ux Disease. Am J Gastroenterol 2013; 108:308 – 328

GERD Treatment – • Nissen fundoplication • LINX • LES E-stim • Endoscopic suturing technique (EndoCinch) • Delivers radiofrequency energy to the OGJ (Stretta) • Transoral plication device (EsophyX). Sham-controlled trials of this device are ongoing.

LINX 5yr F/U: Esophageal pH Monitoring

Ganz RA, et al. Magnetic Sphincter Augmentation for Gastroesophageal Reflux at 5 Years: Final Results of a Pilot Study Show Long-Term Acid Reduction and Symptom Improvement. J Laparoendosc Adv Surg Tech A 2015 Oct;25(10):787-92.

LINX 5 year F/U: Summary of Key Outcomes

Ganz RA, et al. Magnetic Sphincter Augmentation for Gastroesophageal Reflux at 5 Years: Final Results of a Pilot Study Show Long-Term Acid Reduction and Symptom Improvement. J Laparoendosc Adv Surg Tech A 2015 Oct;25(10):787-92.

Case 1: 46yo F with “refractory GERD” • 46yo female referred by her local ENT and allergist for GI consultation re: "refractory GERD" in a patient with allergic rhinitis, chronic sinusitis, and asthma. (Extra esophageal symptoms) • Pt states she has had recurrent pneumonias since a child and frequent hoarseness and laryngitis. She has had recurrent sinus infections that were treated with frequent antibiotics. • She denies symptoms of heartburn, regurgitation, frequent belching, nausea, or vomiting. (No typical GERD symptoms) • Trials of PPIs and H2RA did not improve her symptoms. • EGD with esophageal biopsies: (-) EoE

Case 1: 46yo F with “refractory GERD” 24hr esophageal pH/impedance monitoring results:

Fraction Time pH < 4 Total: 1.1% (NL< 5%) Fraction Time pH < 4 Upright :1.9% (NL< 5%) Fraction Time pH < 4 Recumbent: 0% (NL< 5%) Fraction Time pH < 4 Post prandial: 2.3% (< 5%) No. Acid Reflux: 40 (NL