Hold the Wrap! There is so much more to be done!

Transcription

1 Hold the Wrap! There is so much more to be done! (Well, a few things that can be done.) (Well, not all that much, really ) (But Blair has never killed anyone with a PPI!) Nicholas Shaheen, MD, MPH Center for Esophageal Diseases and Swallowing University of North Carolina 1 Objectives Describe the characteristics of people with incomplete response to PPI Review the options for further therapy in patients who are incompletely responsive to PPI Review the data on randomized trials of medical vs. surgical therapy of GERD 2 1

2 Premise #1 It is highly unlikely that Kevin s patient is currently suffering from acid reflux 3 What Can We Expect Epidemiologically? 4 2

3 Do Pts w/ GERD Symptoms Despite PPIs have Abnormal Acid Exposures? 5 Charbel S et al, Am J Gastroenterol 2005;100: Systematic review of symptom response with PPI therapy in EE and ENRD Pooled symptom relief at 4 weeks (%) *** EE (n=705) 36.7 ENRD (n=1854) 0 PPI Placebo ***p<0.001 vs EE 6 Dean et al, Clin Gastroenterol Hepatol 2004; 2: 656 3

4 So it is likely l that t patients t symptomatic despite BID PPI do not have abnormal acid exposures. 7 Premise #2 If Kevin s patient is suffering from acid reflux, it is likely because he is lying to Kevin! 8 4

5 Compliance With Medications Coping With GERD Internet Survey (N = 587) Fairly regularly but sometimes forget 6% Do not take medication 17% As needed 22% Regularly, as directed by their physician 55% 9 But Wait, It is Even Worse BE Non-BE P value Number of patients 10,159 48,965 Medication ownership ratio On PPI at 60 days 4,455 (43.9%) 15,665 (32.0%) < On PPI at 90 days 4,341 (42.7%) 15,071 (30.7%) < On PPI at 120 days 4,229 (41.6%) 14,170 (28.9%) < On PPI at 180 days 4,027 (39.6%) 13,469 (27.5%) < On PPI at 240 days 3,958 (39.0%) 13,287 (27.1%) < On PPI at 270 days 3,907 (38.5%) 12,972 (26.5%) < On PPI at 360 days 3,807 (37.5%) 12,714 (26.0%) < Number of patients with at least one PPI prescription 10 6,765 29,567 El Serag et al. Am J Gastroenterol

6 Premise #3 If Kevin s patient is experiencing acid reflux, and is not lying to Kevin (remember, the pt is a lawyer), he still has several other viable options before undergoing the knife 11 What are the Options for GERD Partially Responsive to PPI? Double same PPI Switch to another PPI How crazy is that? Add on an H2 blocker qhs Add Baclofen Lose weight 12 6

7 Twice daily PPI therapy for esophageal syndrome patients with an inadequate symptom response to once daily PPI therapy 13 Kahrilas PJ, Shaheen NJ, Vaezi MF. Gastroenterology 2008; 135: What Do You Get from Switching PPI? RCT of pts with Esomeprazole Lansoprazole 40 mg once 30 mg twice residual sympts on daily (n = 138) daily (n = 144) Lanso 30 QD Pts randomized to BID Lanso vs QD Eso Symptom improvement, % (n) P value Heartburn 83.3 (115) 83.3 (120) 1.00 Acid regurgitation 76.8 (106) 72.9 (105).58 Epigastric pain 67.4 (93) 61.1 (88) Fass R et al. Clin Gastroenterol & Hepatol

8 H2 Receptor Antagonists Improve Nocturnal Acid Breakthrough? Effect on Nocturnal Acid Breakthrough Effect on Intragastric ph 15 Xue S et al. Aliment Pharmacol Ther 2001;15: Then This Came Along % with any NAB 16 Fackler WK et al. Gastroenterology 2002;122:

9 GABA B receptor agonist Inhibits TLESRs 9 Healthy controls, 9 GERD, p-prandial 39% SE s Dizziness Nausea Vomiting Baclofen 17 Vela M et al. Aliment Pharmacol Ther 2003;17: Effect of Baclofen on Esophageal Acid Exposure Placebo-controlled trial, 16 controls and 28 ENRD patients GERD Time ph <4, % * P < Baseline 0 Baclofen Controls 5 Baseline Placebo Time ph <4, % 2 1 * P < Baseline Baclofen 0 Baseline Placebo 18 Ciccaglione AF, et al. Gut. 2003:52:

10 What is the effect of weight gain on GERD symptoms? Mu ultivariate Odds Ratio for Reflux Symptoms P <.001 for trend < Body Mass Index 19 Jacobson BC et al. NEJM, 2006;354: What Can You Get From Weight Loss? Prospective cohort study a weight loss program Exercise program, dietary advice, behavioral therapy 37% of pts had GERD at baseline by RDQ 20 Singh M et al. Obesity

11 Putative Advantages of Surgical Anti-Reflux Procedures They are more effective at controlling acid reflux than medications They are durable They are safe They prevent esophageal cancer 21 An RCT of Medical vs. Surgical Therapy: the LOTUS Trial Figure Legend: LARS indicates laparoscopic antireflux surgery. 22 JAMA. 2011;305(19): doi: /jama

12 How Durable is an ARS? 23 Spechler SJ et al, JAMA 2001;285: So an Anti-Reflux Surgery is Certainly not Forever 24 12

13 Like Any Surgery, There are Risks and Side Effects Bleeding Infection Perforation Gas-Bloat Persistent Dysphagia Diarrhea 25 How About Surgery for Extra- Esophageal Symptoms? 26 Wright RC and Rhodes KP, Am J Surg 2003;185:

14 Esophageal Symptom Generation Chemo-stimulation Acid mediated Reflux Mechano-stimulation Volume mediated Heartburn Regurgitation Chest pain Cough 27 Kahrilas PJ So Who Are Today s PPI Partial Responders? Acid-mediated disease Likely a small proportion Mechanostimulation/non-acidic Perhaps mediated by high numbers of gaseous or mixed reflux events Hypersensitivity Normal overall reflux numbers and content, but more likely to be symptomatic Positive symptom index on MII-pH testing Functional Heartburn Non-reflux mediated diseases 14

15 29 So Who Are Today s PPI Partial Responders? Acid-mediated disease Likely a small proportion Mechanostimulation/non-acidic Perhaps mediated by high numbers of gaseous or mixed reflux events Hypersensitivity Normal overall reflux numbers and content, but more likely to be symptomatic Positive symptom index on MII-pH testing Functional Heartburn Non-reflux mediated diseases Suggested Algorithm for GERD Partially Responsive to PPI 30 Dellon ES & Shaheen NJ. Gastroenterology

16 Conclusions Because of the efficacy of acid inhibition with PPI in healing erosive esophagitis, symptom control has become the main battleground in GERD A substantial proportion of GERD sufferers are not happy with their symptom control Most subjects reporting ongoing symptoms do not have pathologic acid exposures Current choices for add-on or substitute therapy exist, but are suboptimal Surgery often does not provide durable relief A better understanding of the pathophysiology of residual symptoms would aid in development of Rx 31 16