Managing Opioid-Induced Constipation

THURSDAY NOVEMBER 14 7:00 am –11:15 am 12:30 pm –1:00 pm 2:00 pm –5:00 pm

FRIDAY NOVEMBER 15 7:00 am –11:30 am 1:45 pm –5:00 pm

SATURDAY NOVEMBER 16 7:00 am –12:45 pm 1:45 pm –5:00 pm

This activity is jointly provided by Global Education Group and Integritas Communications.

This activity is supported by an educational grant from AstraZeneca.

CME/MEDICAL COMMUNICATIONS INQUIRIES info@integritasgrp.com integritasgrp.com

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FACULTY

Jeffrey A. Gudin, MD Attending Physician Englewood Hospital and Medical Center, New Jersey Clinical Associate Professor, Anesthesiology and Perioperative Medicine, Rutgers New Jersey Medical School Board Certified in Pain Management, Anesthesiology, Palliative Care and Addiction Medicine Englewood, New Jersey Dr Jeffrey Gudin earned his medical degree from Albany Medical College in Albany, New York. Following a transitional internship in surgery, medicine, and anesthesiology at St. Barnabas Medical Center in Livingston, New Jersey, he completed his residency in anesthesiology at the Yale University School of Medicine and his fellowship at the Yale Center for Pain Management in New Haven, Connecticut. While in New Haven, Dr Gudin also trained in addiction medicine and directed a substance abuse treatment center. Prior to his current role, Dr Gudin was Director of Pain Management and Palliative Care at Englewood Hospital and Medical Center for 19 years. He is a Clinical Associate Professor of Anesthesiology and Perioperative Medicine at the Rutgers New Jersey Medical School in Newark. He remains active in teaching and research, and has lectured internationally on a variety of topics in pain management, palliative care, and addiction medicine.

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TARGET AUDIENCE The educational design of this activity addresses the needs of physiatrists, pain specialists, and other clinicians involved in the identification and multidisciplinary management of patients with opioid-induced constipation.

STATEMENT OF NEED/PROGRAM OVERVIEW Constipation, the most common side effect of chronic opioid therapy, is a constellation of symptoms that include infrequent or incomplete bowel movements, abdominal pain or bloating, and the need to strain when having a bowel movement.1,2 In addition to constipation-related discomfort, opioid-induced constipation (OIC) produces significant health and quality-of-life burdens.3,4 Poorly managed OIC can lead patients to reduce or skip opioid doses, thereby decreasing adherence, increasing pain-related biopsychosocial complications, diminishing functional gains, and compromising overall outcomes.4-6 During this live Interactive Professor™ session, the prerecorded threedimensional representation of the expert faculty will present practical approaches to multimodal management of OIC. Presenting faculty will discuss initiation and escalation of appropriate therapies, including pharmacologic treatment modalities that have been specifically approved for OIC by the US Food and Drug Administration (FDA).7,8 This session will review the most recent evidence-based guidelines for management of OIC,9 as well as effective patient communication strategies for discussing opioid-related bowel issues and available treatment options. Through an interactive casebased presentation, participants will gain experience in a hands-on approach to bowel assessment, management strategies, and implementation of individualized treatment plans for patients with OIC. Additionally, attendees will gain access to our online Clinical Resource Center for OIC.

REFERENCES 1. Coyne KS, LoCasale RJ, Datto CJ, Sexton CC, Yeomans K, Tack J. Opioid-induced constipation in patients with chronic noncancer pain in the USA, Canada, Germany, and the UK: descriptive analysis of baseline patient-reported outcomes and retrospective chart review. Clinicoecon Outcomes Res. 2014;6:269-281.

2. Camillieri M, Drossman DA, Becker G, Webster LR, Davies AN, Mawe GM. Emerging treatments in neurogastroenterology: a multidisciplinary working group consensus statement on opioid-induced constipation. Neurogastroenterol Motil. 2014;26(10):1386-1395.

3. LoCasale RJ, Datto C, Wilson H, Yeomans K, Coyne KS. The burden of opioid-induced constipation: discordance between patient and health care provider reports. J Manag Care Spec Pharm.

2016;22(3):236-245.

4. Andresen V, Banerji V, Hall G, Lass A, Emmanuel AV. The patient burden of opioid-induced constipation: new insights from a large, multinational survey in five European countries. United European Gastroenterol J. 2018;6(8):1254-1266.

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5. Harris JD. Management of expected and unexpected opioid-related side effects. Clin J Pain.

2008;24(suppl 10):S8-S13.

6. Gupta SH, Patel H, Scopel J, Mody RR. Impact of constipation on opioid therapy management among longterm opioid users, based on a patient survey. J Opioid Manag. 2015;11(4):325-338.

7. Chey WD, Webster L, Sostek M, Lappalainen J, Barker PN, Tack J. Naloxegol for opioid-induced constipation in patients with noncancer pain. N Engl J Med. 2014;370(25):2387-2396.

8. Argoff CE, Brennan MJ, Camilleri M, et al. Consensus recommendations on initiating prescription therapies for opioid-induced constipation. Pain Med. 2015;16(12):2324-2337.

9. Crockett SD, Greer KB, Heidelbaugh JJ, Falck-Ytter Y, Hanson BJ, Sultan S; American Gastroenterological Association Institute Clinical Guidelines Committee. American Gastroenterological Association Institute guideline on the medical management of opioid-induced constipation.

Gastroenterology. 2019;156(1):218-226.

EDUCATIONAL OBJECTIVES After completing this activity, the participant should be better able to: • Describe the clinical profiles and prescribing recommendations for FDAapproved treatment options for OIC • Discuss recent updates to national evidence-based guidelines on the management of OIC • Tailor bowel regimens for patients with opioid-treated chronic pain who do not respond adequately to traditional laxative therapy

PROGRAM AGENDA 0 minutes–3 minutes:

Preactivity Assessment

4 minutes–8 minutes: 9 minutes–14 minutes: 15 minutes–27 minutes: 28 minutes–30 minutes:

Why Are We Here? Hidden Burdens of OIC New Recommendations in OIC Management Case-Based Updates on OIC Management Postactivity Assessment

PHYSICIAN ACCREDITATION STATEMENT This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Global Education Group (Global) and Integritas Communications. Global is accredited by the ACCME to provide continuing medical education for physicians.

This CME/CE activity complies with all requirements of the federal Physician Payment Sunshine Act. If a reportable event is associated with this activity, the accredited provider managing the program will provide the appropriate physician data to the Open Payments database.

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PHYSICIAN CREDIT DESIGNATION Global designates this live activity for a maximum of 0.5 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

ABIM MOC RECOGNITION STATEMENT Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 0.5 medical knowledge MOC points in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

GLOBAL CONTACT INFORMATION For information about the accreditation of this program, please contact Global at 303-395-1782 or cme@globaleducationgroup.com.

INSTRUCTIONS TO RECEIVE CREDIT In order to receive credit for this activity, the participant must attend the session and complete the program evaluation.

FEE INFORMATION AND REFUND/ CANCELLATION POLICY There is no fee for this educational activity.

DISCLOSURE OF CONFLICTS OF INTEREST Global requires instructors, planners, managers and other individuals, and their spouse/life partner, who are in a position to control the content of this activity to disclose any real or apparent conflict of interest they may have as related to the content of this activity. All identified conflicts of interest are thoroughly vetted by Global for fair balance, scientific objectivity of studies mentioned in the materials or used as the basis for content, and appropriateness of patient care recommendations.

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The faculty reported the following financial relationships or relationships to products or devices they or their spouse/life partner have with commercial interests related to the content of this CME activity: Jeffrey A. Gudin, MD Consultant/Independent Contractor: AcelRx Pharmaceuticals, Inc., BioDelivery Sciences International, Inc., Daiichi-Sankyo, Inc., GlaxoSmithKline, Mallinckrodt, Nektar Therapeutics, Purdue Pharma L.P., Quest, Salix Pharmaceuticals, Scilex Pharmaceuticals, Inc., Semnur Pharmaceuticals. Speakers Bureau: BioDelivery Sciences International, Inc., Daiichi-Sankyo, Inc., Scilex Pharmaceuticals, Inc. The planners and managers reported the following financial relationships or relationships to products or devices they or their spouse/life partner have with commercial interests related to the content of this CME activity: Lindsay Borvansky Andrea Funk Liddy Knight Ashley Cann Stacey Ullman, MHS Rose O’Connor, PhD, CHCP

Nothing to disclose Nothing to disclose Nothing to disclose Nothing to disclose Nothing to disclose Nothing to disclose

DISCLOSURE OF UNLABELED USE This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. Global and Integritas Communications do not recommend the use of any agent outside of the labeled indication(s).

The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of any organization associated with this activity. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.

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DISCLAIMER Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed in this activity should not be used by clinicians without evaluation of patient conditions and possible contraindications on dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.

MANAGING OPIOID-INDUCED CONSTIPATION Translating Guidelines Into Patient Care

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GUIDELINES NCCN Clinical Practice Guidelines in Oncology: Adult Cancer Pain.

National Comprehensive Cancer Network » https://www.ncbi.nlm.nih.gov/pubmed/31390582

American Gastroenterological Association Institute guideline on the medical management of opioid-induced constipation.

Crockett SD, Greer KB, Heidelbaugh JJ, Falck-Ytter Y, Hanson BJ, Sultan S; for the American Gastroenterological Association Institute Clinical Guidelines Committee. Gastroenterology.

2019;156(1):218-226. » https://www.gastrojournal.org/article/S0016-5085(18)34782-6/pdf

PATIENT RESOURCES Opioid Induced Constipation Conversation Guide American Chronic Pain Association This patient tool can be completed prior to the visit with the health care provider to guide a meaningful conversation about bowel habits and constipation symptoms. » https://www.theacpa.org/wp-content/uploads/2017/08/ACPA-Opioid Constipation Chart-V4.pdf

CLINICAL ASSESSMENT TOOLS Bowel Function Index The Bowel Function Index provides a numerical score for the prior 7 days, based on ease of defecation, feeling of incomplete evacuation, and personal judgment of constipation; it should not be self-administered. » https://www.exchangecme.com/resourcePDF/chronicpain/BFI2019.pdf

Bristol Stool Chart Bladder and Bowel Foundation This visual scale is used to help patients characterize their stool. It classifies the most commonly passed stool forms into 7 types. » https://www.bladderandbowel.org/wp-content/uploads/2017/05/BBC002 Bristol-Stool-ChartJan-2016.pdf

Patient Assessment of Constipation Symptoms (PAC-SYM) The PAC-SYM is a 12-item questionnaire of patient-reported symptoms during the 2 prior weeks, with 3 subscales tracking bowel movements, rectal symptoms, and abdominal symptoms.

Psychometric validation of a constipation symptom assessment questionnaire.

Frank L, Kleinman L, Farup C, Taylor L, Miner P Jr. Scand J Gastroenterol. 1999;34(9):870-877. » https://eprovide.mapi-trust.org/instruments/patient-assessment-of-constipation-symptoms

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SUGGESTED READINGS OIC Overview Insights into the role of opioid receptors in the GI tract: experimental evidence and therapeutic relevance.

Galligan JJ, Sternini C. Handb Exp Pharmacol. 2017;239:363-378. » https://link.springer.com/chapter/10.1007%2F164 2016 116

Impact of constipation on opioid therapy management among long-term opioid users, based on a patient survey.

Gupta S, Patel H, Scopel J, Mody RR. J Opioid Manag. 2015;11(4):325-338. » https://www.wmpllc.org/ojs/index.php/jom/article/view/188

Management of OIC Naloxegol for opioid-induced constipation in patients with noncancer pain.

Chey WD, Webster L, Sostek M, Lappalainen J, Barker PN, Tack J. N Engl J Med. 2014;370(25):2387-2396. » http://www.nejm.org/doi/pdf/10.1056/NEJMoa1310246

A randomized, placebo-controlled trial of lubiprostone for opioid-induced constipation in chronic noncancer pain.

Jamal MM, Adams AB, Jansen JP, Webster LR. Am J Gastroenterol. 2015;110(5):725-732. » https://insights.ovid.com/crossref?an=00000434-201505000-00020

Randomized phase III and extension studies of naldemedine in patients with opioid-induced constipation and cancer.

Katakami N, Haruda T, Murata T, et al. J Clin Oncol. 2017;35(34):3859-3866. » https://ascopubs.org/doi/full/10.1200/JCO.2017.73.0853?url ver=Z39.88-2003&rfr id=ori%3Arid%3Acrossref.org&rfr dat=cr pub%3Dpubmed

Efficacy of treatments for opioid-induced constipation: a systematic review and meta-analysis.

Nee J, Zakari M, Sugarman MA, et al. Clin Gastroenterol Hepatol. 2018;16(10):1569-1584.e2. » https://www.cghjournal.org/article/S1542-3565(18)30087-9/fulltext

Randomized, double-blind trial of oral methylnaltrexone for the treatment of opioid-induced constipation in patients with chronic noncancer pain.

Rauck R, Slatkin NE, Stambler N, Harper JR, Israel RJ. Pain Pract. 2017;17(6):820-828. » https://onlinelibrary.wiley.com/doi/full/10.1111/papr.12535

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Randomised clinical trial: the long-term safety and tolerability of naloxegol in patients with pain and opioid-induced constipation.

Webster L, Chey WD, Tack J, Lappalainen J, Diva U, Sostek M. Aliment Pharmacol Ther.

2014;40(7):771-779. » https://onlinelibrary.wiley.com/doi/full/10.1111/apt.12899

Long-term safety and efficacy of subcutaneous methylnaltrexone in patients with opioid-induced constipation and chronic noncancer pain: a phase 3, open-label trial.

Webster LR, Michna E, Khan A, Israel RJ, Harper JR. Pain Med. 2017;18(8):1496-1504. » https://academic.oup.com/painmedicine/article/18/8/1496/4049466

Long-term use of naldemedine in the treatment of opioid-induced constipation in patients with chronic noncancer pain: a randomized, double-blind, placebo-controlled phase 3 study.

Webster LR, Nalamachu S, Morlion B, et al. Pain. 2018;159(5):987-994. » https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916485/

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