improving the diagnosis and management of opioid … constipation to optimize outcomes of patients...

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Improving the Diagnosis and Management of Opioid-induced Constipation to Optimize Outcomes of Patients with Chronic Pain

Sponsored by Integrity Continuing Education, Inc.

Supported by an educational grant from Salix Pharmaceuticals, Inc.

2

Faculty Affiliation

Peter Pryzbylkowski, MDAttending Physician

Pain MedicineRelievus Pain ManagementHammonton, New Jersey

3

Faculty Disclosures

▪ Speakers Bureau: Astra Zeneca, Daiichi Sankyo

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▪ Describe the prevalence of opioid-induced constipation (OIC) and its effect on patient health, quality of life (QOL), and adequacy of pain management

▪ Identify clinical barriers to accurate assessment and diagnosis of OIC

▪ Describe the recommended assessment of patients with OIC and indications for initiation of treatment

▪ Compare the relative efficacy and safety of currently available therapies for OIC

Learning Objectives

5

Everyday Burden of Chronic Pain Among Adults in the United States

Nahin, et al. J Pain. 2015;16(8):769–780.

2012 National Health Interview Survey

2.1%

4.5% 4.6%

0.0%

1.0%

2.0%

3.0%

4.0%

5.0%

A little pain A little to a lot of pain A lot of pain

Ad

ult

s re

po

rtin

g p

ain

o

ccu

rrin

g ev

ery

day

(%

)

6

Prescription Opioid Analgesic Use in the US

Dart RC, et al. NEJM. 2015;372:241-248.

Prescriptions Dispensed for Opioid Analgesics

No

. of

Pre

scri

pti

on

s D

isp

en

sed 67,000,000

61,000,000

54,000,000

48,000,000

42,000,000

0

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Effects of Opioid Action

*Studies suggest 𝛿 and 𝜅 receptors may make a small but potentially clinically significant contribution ORL-1, opioid receptor-like-1, GI, gastrointestinal.

Rumman A, et al. Exp Rev Qual Life Canc Care. 2016;1(1):25-35.Kumar L, et al. Gastroenterol Res Pract. 2014;2014:141737.

Central(𝜇,𝛿,𝜅, & ORL-1

receptors)

Possible alteration of autonomic activity May reduce GI propulsion

Enteric(𝜇 receptors*)

Reduced bowel tone and contractility Prolonged transit time

Increased frequency and strength of circular muscle contractions

Increased nonpropulsive contractions and enhanced fluid absorption

Reduced longitudinal muscle propulsive contractions

Exacerbates trend to harder, drier stools

Increased anal sphincter tone and decreased reflex relaxation in response to rectal distension

Contributes to difficulty in rectal evacuation

8

Opioid-induced Bowel Dysfunction

Opioid-induced bowel dysfunction

Constipation NBSDelayed gastric

emptyingVomitingNausea GERD

GERD, gastroesophageal reflux disease; NBS, normal bowel sounds.

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Frequency of Constipation with Oral Opioid Treatment

Note: Each symbol represents one study, and size of the symbol reflects the size of the trial, according to the scale at the right.RCTs, randomized control trials.Kalso, et al. Pain. 2004;112:372–380; Camilleri et al. Am J Gastroenterol 2011;106:835–842.

• Constipation is the most common GI complaint associated with opioid treatment

• Meta-analysis of 8 RCTs (N=1,114) found that 41% of patients suffered from OIC after 8 weeks of therapy

0 20 40 60 80 100Constipation (%) with placebo

100

80

60

40

20

0

Constipation (%) with opioid

400

200

0

10

Consequences of OIC

Early OIC

• Impaired QOL• Poor adherence• Medical complications

Later OIC

• Development of opioid-induced bowel dysfunction• Poor adherence or discontinuation

Long-term Implications

• Unnecessary or inadequate pain management• Increased surgical events, ED visits, and hospitalizations

ED, emergency department.Adapted from: Wick JY. 2016. Retrieved from http://www.pharmacytimes.com/publications/issue/2016/july2016/ opioids-and-constipation; Bell TJ, et al. Pain Med. 2009;10(1):35-42; Looström H, et al. Arch Oral Biol. 2011;56(4): 395-400; Pappagallo M.Am J Surg. 2001;182:11S-18S; Gupta S, et al. J Opioid Manag. 2015;11(4):325-338.

http://www.pharmacytimes.com/publications/issue/2016/july2016/opioids-and-constipation

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Patient-reported Impact of OIC on QOL

Patients Reporting Measure (%)

Rauck RL, et al. Pain Practice. 2016.

38

43

45

46

49

84

Impaired work performance

Limits ability to leave house

Limits social interaction

Limits sexual intimacy

Inability to perform daily activities

Impacts dietary choices

12

Patient-reported Impact of OIC on Mental Health

49

49

30

41

32

90

Embarrassment

Depression

Low-self esteem

Social isolation

Anger

Frustration/irritability

Patients Reporting Presence of Measure (%)


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Constipation Is Associated with Increased Healthcare Utilization in Patients Undergoing Opioid Therapy

*Non-cancer patients receiving opioid therapy

Adapted from Olufade et al. Am Health Drug Benefits. 2017;10(2):79-86.

Healthcare utilization

(all-cause) Patients with

constipation, N (%)Patients w/o

constipation, N (%)P

value

Inpatient admission 785 (28.9) 368 (13.5) <.001

ED visits 1612 (59.4) 1279 (47.1) <.001

Outpatient office visits 2579 (95.0) 2476 (91.2) <.001

Other outpatient services 2634 (97.0) 2541 (93.6) <.001

Pharmacy claims 2716 (100.0) 2716 (100.0)

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Constipation Is Associated with Increased Healthcare Costs in Patients Undergoing Opioid Therapy

*Non-cancer patients receiving opioid therapy

Adapted from Olufade et al. Am Health Drug Benefits. 2017;10(2):79-86.

$ (Mean, 95% CI)

Healthcare costs (all-cause)Patients with constipation

Patients w/o constipation

Pvalue

Inpatient admission46,817

(33,982-59,652)33,884

(27,999-39,769).186

ED visits703

(653-754)429

(395-464)<.001

Outpatient office visits843

(812-875)605

(584-626)<.001

Other outpatient services 8534

(7931-9136)4457

(4118-4796)<.001

Pharmacy claims 4622

(4343-4900)3627

(3377-3877)<.001

Total 28,234

(24,307-32,160)13,709

(12,618-14,801)<.001

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Recognition and Diagnosis of OIC

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▪ Duration of opioid treatment

▪ Older age

▪ Female sex

▪ Additional factors

– Higher education levels

– Concomitant aspirin use

– Nonsmoker status

▪ Incidence appears unaffected by the opioid route of

administration (oral or transdermal)

Risk Factors for OIC

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Case Study #1: Identification and Diagnosis

▪ Jane, 50-year-old woman

▪ Chronic back pain due to an injury sustained in a vehicle accident 5 years ago

▪ History of mild depression

▪ Inadequate pain management despite NSAID therapy

▪ Initiated on opioid therapy 3 months ago

▪ Currently reports the following symptoms

– Straining

– Incomplete evacuation

– Hard dry stools every 3-4 days

NSAID, nonsteroidal anti-inflammatory drug.

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▪ What type of assessment tools/measures would you apply in evaluating Jane?

▪ How would you determine whether Jane’s constipation is caused exclusively by her opioid treatment or reflects the impact of the treatment along with other constipating factors?

▪ What other conditions would you consider in the differential diagnosis?

Case Study #1: Discussion

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A change when initiating opioid therapy from baseline bowel habits characterized by any of the following:

Definition of OIC

Reduced bowel

movement frequency

Development or worsening of straining to

pass bowel movements

Sense of incomplete

rectal evacuation

Harder stool consistency

Camilleri M, et al. Neurogastroenterol Motil. 2014;26(10):1386-1395.

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Bristol Stool Form Scale

Available at: http://bowelcontrol.nih.gov/Bristol_Stool_Form_Scale_508.pdf

Type Description Image

1 Separate hard lumps, like nuts

2 Sausage-shaped but lumpy

3 Like a sausage or snake but with cracks on its surface

4 Like a sausage or snake, smooth and soft

5 Soft blobs with clear-cut edges

6 Fluffy pieces with ragged edges, a mushy stool

7 Watery, no solid pieces

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Assessment Tools and Outcome Measures

*Could theoretically be collected by an investigator as well as by the patient (eg, defecation frequency; †Reports coming directly from patients about how they feel or function in relation to a health condition and its therapy without interpretation by healthcare professionals or anyone else.;‡Patient-reported outcome measures that directly relate to the patient’s distress and the impact on their daily activities or QOL and are most obviously caused by OIC.

Neurogastroenterol Motil. 2014 October ; 26(10): 1386–1395.

Objective Measures*

• Bowel movement frequency/change in bowel movement frequency

• Time to laxation

• Laxation within 4 hours

• Gastrointestinal (or short bowel) transit time

• Bristol Stool Form scale

Patient-Reported Outcomes†

• Bowel Function Index

• Patient Assessment of Constipation –Symptoms

• Global Clinical Impression of Change

Patient-Reported Burden‡

• Constipation distress

• Patient Assessment of Constipation – QOL

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Bowel Function Index (BFI)

Argoff CE, et al. Pain Medicine. 2015;16(12):2324-2337.

1. Ease of defecation (NAS) during the last 7 days according to patient assessment:

0 = easy / no difficulty100 = severe difficulty

2. Feeling of incomplete bowel evacuation (NAS) during the last 7 days according to patient assessment:

0 = not at all100 = very strong

3. Personal judgement of patient (NAS) regarding constipation during the last 7 days:

0 = not at all100 = very strong

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Patient Assessment of Constipation Symptoms (PAC-SYM)

Slappendel R, et al. Eur J Pain. 2006;10(3):209-217.

Domain Item

Abdominal

• Discomfort in your stomach

• Pain in your stomach

• Bloating in your stomach

• Stomach cramps

Rectal

• Painful bowel movements

• Rectal burning during or after bowel movement

• Rectal bleeding or tearing during or after bowel movement

Stool

• Incomplete bowel movements, like you did not “finish”• Bowel movements that were too hard• Bowel movements that were too small• Straining or squeezing to try to pass a bowel movement• Feeling like you had to pass a bowel movement but could not

(“false alarm”)

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Differential Diagnosis of Constipation

Category Cause

Functional Diet, motility disturbance, sedentary

StructuralAnorectal fissures, hemorrhoids, diverticulitis, mass lesions with obstruction

MetabolicDiabetes, hyperparathyroidism, hypercalcemia, hypokalemia, hypothyroidism, uremia, pregnancy

Neurogenic Stroke, MS, spinal cord injury, brain injury

Psychogenic Anxiety, depression, somatization

DrugsOpioids, anticholinergics, antidepressants, calcium channel blockers, psychotropics, diuretics, levodopa

MS, multiple sclerosis.Arce, et al. Am Fam Physician. 2002;65(11):2283-90.

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Barriers to the Diagnosis of OIC

• Lack of disease awareness

• Failure to ask about constipation

• Screening based on Rome criteria may be inadequate

• Absence of universal diagnostic criteria

• Absence of a standard treatment protocol

• Reluctance to disclose symptoms to clinicians

Clinician-Related Barriers Patient-RelatedBarriers

Nelson, et al. Ther Adv Chronic Dis. 2016;7(2) :121-134.

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Treatment of OIC

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▪ Having established that Jane’s symptoms are primarily due to opioid therapy, what type of initial treatment would you recommend to address her symptoms of constipation?

▪ At what point would you initiate Jane on some form of prescription therapy?


31Webster LR. Pain Med. 2015;16 Suppl 1:S16-21.

Treatment Type Examples Comments

Stool softeners • Docusate

• Ease passage of stool

• May be prescribed in combination

with a laxative

Laxatives

Osmotic

agents

• Polyethylene glycol

solution

• Retain water in the gut• May be mixed with electrolytes to

avoid dehydration

Stimulants• Senna

• Bisacodyl• Increase intestinal motility

Bulk • Not recommended for OIC

Over-the-Counter Treatment Options

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Criteria for Initiating Prescription Treatment of OIC

Argoff CE, et al. Pain Medicine. 2015;16(12):2324-2337.Ueberall et al. J Int Med Res. 2011;39(1):41-50.

Prescription treatments should be considered for patients with a BFI score ≥30 and inadequate response to first-line intervention

Re

lati

ve C

um

ula

tive

Fr

eq

ue

ncy

(%

)

0 10 20 30 40 50 60 70 80 90 100BFI Score

100

90

80

70

60

50

40

30

20

10

0

ReferencePopulation

OICPopulation

7.9%

28.8

95.0%

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Prescription Treatments for OIC

*Indicated to accelerate time to upper and lower GI recovery following partial large or small bowel resection surgery with primary anastomosis

PGE1, prostaglandin E1; PEG, Polyethylene Glycol; BBB, blood-brain barrier.

Agent Mechanism of Action

Lubiprostone• Bicyclic fatty acid derived from PGE1• Increases fluid secretion in the GI tract

Naloxone/ oxycodone

• Naloxone is local (GI) µ-opioid antagonist• Differential bioavailability between naloxone and oxycodone

allows for central effects with diminished peripheral effects

Naloxegol• Polyethylene glycol derivative of naloxone• PEG moiety reduces ability to pass BBB

Methylnaltrexone• Quaternary N-methyl derivative of naltrexone• Decreased lipid solubility reduces ability to cross the BBB

Naldemedine• Naltrexone derivative• Additional side chain confers increased molecular weight and

polar surface area, reducing ability to cross the BBB

Alvimopan* • Competitively binds to GI tract mu-opioid receptors

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Effect of Lubiprostone Treatment on SBM: 12-Week Response Rates

*P<.05; †Overall responders were defined as reporting at least a moderate response (≥1 SBM from baseline frequency) as well as a full response (≥3 SBMs/wk) for ≥9 of 12 wks.

BID, twice daily; SBM, spontaneous bowel movement.

Jamal MM, et al. Am J Gastroenterol 2015; 110:725-732.

Pe

rce

nta

ge o

f SB

MR

esp

on

der

s

0 2 4 6 8 10 12Treatment Week

70

60

50

40

30

20

10

0

Lubiprostone 24 µg BID

Placebo BID

Overall†

P=.030

27.1

18.9

**

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Treatment with Lubiprostone Improves Symptoms of OIC

*Straining, for stool consistency; †stool consistency, for straining; ‡abdominal bloating, for abdominal discomfort; and §abdominal discomfort , for abdominal bloating.

Jamal MM, et al. Am J Gastroenterol 2015; 110:725–732.

Straining

Ove

rall

Me

an C

han

ge

fro

m B

ase

line

0

−0.5

−1.0

−1.5

−2.0

−2.5

Stool Consistency

ConstipationSeverity

AbdominalBloating

AbdominalDiscomfort

Placebo BID

Lubiprostone 24 µg BID

P=.004

P=.004*

P<.001

P<.001†

P=.010P=.155

P=.155‡

P=.063

P=.127§

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Most Common Treatment-related AEs (>1%) with Lubiprostone

Spierings ELH, et al. Pain Pract. 2015;16:985-993.

Adverse Event (AE) Preferred TermLubiprostone 24 µg BID

(N = 439) n (%)

At least 1 treatment-related AE 108 (24.6)

Nausea 22 (5.0)

Diarrhea 20 (4.6)

Headache 7 (1.6)

Vomiting 6 (1.4)

Abdominal pain lower 5 (1.1)

Flatulence 5 (1.1)

Muscle spasms 5 (1.1)

Back pain 5 (1.1)

Anemia 5 (1.1)

37

Naloxone Treatment in Combination with Oxycodone (OXN)

*Paired t-test: OXN2001 P=.0002; OXN9001 P<.0001; and Total P<.0001.

Koopmans, et al. Curr Med Res Opin 2014; 30:2389-2396.

Combination treatment with a fixed 2:1 ratio of prolonged-release oxycodone/naloxone improved bowel function and reduced the use of laxatives in patients with OIC.

OXN2001• Patients with cancer-related

pain randomized to OXN PR for 4 weeks

OXN9001• Patients with non-cancer-

related pain randomized to OXN PR for 12 weeks.

Screening Start of End ofTreatment Point Treatment

Me

an B

FI S

core

100

90

80

70

60

50

40

30

20

10

0

OXN2001

OXN9001

Total

*

38

Safety of Naloxone and Oxycodone

Sandner-Kiesling A, et al. Int J Clin Prac. 2010;64(6):763-774.

Adverse EventOxycodone PR/Naloxone PR

(N=238) n (%)

Any AE 211 (81.8)

GI disorders 94 (36.4)

Constipation 40 (15.5)

Diarrhea 18 (7.0)

General disorders and administration site conditions 28 (10.9)

Infections and infestations 104 (40.3)

Musculoskeletal and connective tissue disorders 104 (40.3)

Arthralgia 23 (8.9)

Back pain 35 (13.6)

Osteoarthritis 16 (6.2)

Nervous system disorders 58 (22.5)

Headache 18 (7.0)

Psychiatric disorders 31 (12.0)

Respiratory, thoracic and mediastinal disorders 34 (13.2)

Skin and subcutaneous tissue disorders 41 (15.9)

39

Response to Treatment with Naloxegol

ITT, intention-to-treat.

Chey, et al. NEJM. 2014; 370:2387-2396.

29.4 29.3

40.8

34.9

44.439.7

0

10

20

30

40

50

Study 04 Study 05

Pat

ien

ts (

%)

Placebo Naloxegol, 12. 5 mg Naloxegol, 25 mg

Response Rates in the ITT Population

**

*

Relative Risk (95% CI) 1.38 (1.06-1.80) 1.51 (1.17-1.95) 1.19 (0.91-1.55) 1.35 (1.05-1.74)

P Value 0.02 0.001 0.20 0.02

No. Needed to Treat 8.8 6.7 17.8 9.7

N=214 N=213 N=214 N=232 N=232 N=232

40

Response to Naloxegol in Patients with an Inadequate Response to Laxatives

LIR, laxative inadequate response.

Chey, et al. NEJM. 2014; 370:2387-2396.

28.8 31.4

42.6 42.448.7 46.8

0

10

20

30

40

50

60

Study 04 Study 05

Pat

ien

ts (

%)

Placebo Naloxegol, 12. 5 mg Naloxegol, 25 mg

Response Rates in the LIR Population

** *

Relative Risk (95% CI) 1.48 (1.04-2.11) 1.69 (1.21-2.37) 1.35 (0.97-1.88) 1.49 (1.08-2.06)

P Value .03 .002 .07 .01

No. Needed to Treat 7.2 5.0 9.1 6.5

N=118 N=115 N=117 N=121 N=125 N=124

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Safety of Treatment with Naloxegol

aPercentage data based on the number of patients in each treatment group and category; bOccurring during the treatment period; cOnly includes events that included permanent discontinuation of IP.IP, investigation product; LIR, laxative-inadequate responder.

Tack, et al. United Eur Gastroenterol J. 2015, Vol. 3(5) 471–480.

Any Event, n (%)b

Patients, n (%)a

Placebo(n = 238)

Naloxegol 12.5 mg(n = 237)

Naloxegol 25 mg(n = 241)

Any AE 119 (50.0) 120 (50.6) 152 (63.1)

Serious AE 13 (5.5) 7 (3.0) 8 (3.3)

AE leading to discontinuation of IPc 11 (4.6) 8 (3.4) 24 (10.0)

Death 0 0 0

Treatment-emergent AEs (≥3% in any treatment group)

Abdominal pain 13 (5.5) 18 (7.6) 38 (15.8)

Diarrhea 12 (5.0) 16 (6.8) 25 (10.4)

Fall 8 (3.4) 6 (2.5) 2 (0.8)

Nausea 7 (2.9) 15 (6.3) 20 (8.3)

Vomiting 5 (2.1) 6 (2.5) 9 (3.7)

Back pain 5 (2.1) 5 (2.1) 9 (3.7)

Headache 4 (1.7) 8 (3.4) 10 (4.1)

Flatulence 4 (1.7) 5 (2.1) 15 (6.2)

Upper abdominal pain 4 (1.7) 1 (0.4) 8 (3.3)

Hyperhidrosis 0 1 (0.4) 10 (4.1)

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Efficacy of Methylnaltrexone

RFBM, rescue-free bowel movement; MNTX, methylnaltrexone; OLE, open-label extension.

Viscusi, et al. Reg Anesth Pain Med 2016;41: 93–98.

9.7

45.9

0

10

20

30

40

50

60

70

80

PlaceboTreatmentDuring RCT

(n=134)

MNTXTreatmentDuring OLE

(n=134)

Pat

ien

ts W

ith

RFB

M W

ith

in

4 H

ou

rs o

f D

ose

(%

)

9.0

34.5

0

10

20

30

40

50

60

70

80

PlaceboTreatmentDuring RCT

(n=134)

MNTXTreatmentDuring OLE

(n=134)

Infe

ctio

ns

Re

sult

ing

in R

FBM

Wit

hin

4 H

ou

rs o

f D

ose

(%

)

43

Efficacy of Oral Methylnaltrexone for OIC in Patients with Chronic Noncancer Pain

Dosing days resulting in RFBMs within 4hours of dosing (%) Responders during ≥ 9 of 12weeks (%)

*P<.05; **P = .03; †P = .005; ‡P = .02

Adapted from: Rauck et al. Pain Practice. 2017;17:820–828.

Do

sin

g d

ays

that

re

sult

ed

in R

FBM

sw

ith

in 4

h (

%)

0 1 2 3 4 5 6 7 8 9 10 11 12Time (wk)

35

30

25

20

15

10

* *

** *

* **

*

*** *

**

*

* *

*

Methylnaltrexone 150 mgMethylnaltrexone 450 mg

Methylnaltrexone 300 mgPlacebo

QD Period PRN Period

40.5

29.9

0

10

20

30

40

50

60

70

80

90

100

MNTX 450 mg(n = 200)

Placebo(n = 201)

Ove

rall

resp

on

de

rs (

%)

‡

44

Safety of Methylnaltrexone Treatment

▪ Meta-analysis of 7 studies found that patients treated with MNTX experienced the following:

▪ Incidence of MNTX-related serious AEs was 0.2%

RR 95% CI N I2

Abdominal pain 2.38 1.75-3.23 1,412 60%

Nausea 1.27 0.90-1.78 1,412 12%

Diarrhea 1.45 0.94-2.24 1,258 45%

RR, respiratory rate.

Siemens W, et al. Therapeutics and Clinical Risk Management. 2016;12:401-412.

45

Treatment with Naldemedine for OIC Is Associated with a Higher Response Rate vs Placebo

Hale et al. Lancet Gastroenterol Hepatol 2017;2:555–64.

COMPOSE-1

100

90

80

70

60

50

40

30

20

10

0

Pat

ien

ts (

%)

COMPOSE-2

47.6%n=273

52.5%n=276

34.6%n=272

33.6%n=274

Difference: 13.0% (4.8–21.3)

P=.0020

Difference: 18.9% (10.8–27.0)

P<.0001

Naldemedine

Placebo

46

Agent Mechanism of ActionClinical Phase

AxelopranPeripheral µ-opioid receptor antagonist

(PAMORA)

II

Alvimopan III

Linaclotide Guanylyl cyclase C receptor agonist II

TRV-130µ-opioid agonist (stabilizes G-protein receptor

conformations, prevents β-arrestin-2 activation)III

Prucalopride Selective, high-affinity 5HT4 receptor agonist III

Emerging Agents for OIC Treatment

47

The Impact of OIC on Long-term Pain Management

48

▪ John, 67-year-old man, presents for annual visit

▪ Initiated on opioid therapy for chronic pain associated with severe osteoarthritis beginning one year ago

▪ Symptoms of pain were improved during the first several months

▪ Patient reports the following over the past three months:

– Significantly diminished capacity for walking, stooping, and lifting/carrying objects

– Difficulty performing basic household chores

Case Study #2: Poor Adherence to Opioid Treatment

49

▪ What are the possible underlying reasons for the inadequacy of John’s level of pain control?

▪ What do you suspect is the most likely explanation?


50

Medication Nonadherence Among Patients Taking Opioid Medication

• 57% of patients reported having taken less opioid medication than prescribed or discontinuing medication due to side effects.

• Among these individuals, 90% reported OIC as the primary reason.

90.0

22.3

26.4

20.5

Constipation

Sedation

Nausea andvomiting

Other


51

OIC Interference with Pain Management

19.4

31.7

44.1

4.8

0

10

20

30

40

50

Pain adequatelymanaged

Pain mostlymanaged

Pain moderatelymanaged

Pain not at allmanaged

Pat

ien

ts R

ep

ort

ing

(%)

LoCasale RJ, et al. J Manag Care Spec Pharm. 2016;22(3):236-245.

52

Patient vs HCP Perceptions of OIC Interference with Pain Management

HCP, healthcare provider. LoCasale RJ, et al. J Manag Care Spec Pharm. 2016;22(3):236-245.

Comparison between patient and HCP responses revealed a discordance between their perceptions of how much OIC interfered with adequate pain management.

4.8 3.9

43.9 40.8

31.6 41.7

19.813.6

0

10

20

30

40

50

60

70

80

90

100

Baseline (n=415) Week 24 (n=103)

Pat

ien

ts (

%)

Complete interference Moderate interference

Little interference No interference

Patient Report: How Much Does Constipation Interfere with Ability to Control Pain

1.7 1.0

25.5 26.2

46.3 50.5

26.5 22.3

0

10

20

30

40

50

60

70

80

90

100

Baseline (n=415) Week 24 (n=103)

HC

Ps

(%)

Not at all managed Moderately managed

Mostly managed Adequately managed

HCP Report: How Much Does OIC Interfere with This Patient’s Adequate Pain Management

53

▪ Upon further questioning, John admits that he often reduces his dose of opioid medication due to the side effects he has been experiencing. He reports that he has been particularly bothered by bouts of constipation, which have increased in frequency since he first began taking opioids.

▪ What approach would you take to addressing John’s lack of adherence to his prescribed regimen?


54

Agreement of Patient- and HCP-Reported OIC Symptoms


The proportion of HCPs who had observed or discussed each OIC symptom reported by patients as being of moderate or greater severity ranged from 1% to 41%.

1.3

4.1

6.0

7.3

9.2

11.3

13.5

14.3

15.8

20.6

27.0

28.5

37.0

40.7

0 5 10 15 20 25 30 35 40 45

Vomiting

GERD

Nausea

Rectal burning/bleeding or tearing duration or after BM

Headache or migraine

Feeling that had to pass but couldn't

Flatulence

Abdominal discomfort

BMs too small

Abdominal bloating

Painful BMs

Incomplete BMs

Straining/squeezing to try to pass

BMs too hard

OIC Symptoms HCP Has Observed or Discussed with Patient, n (%)

OIC

Sym

pto

ms

Re

po

rte

d a

s ≥

Mo

de

rate

by

Pat

ien

t n = 190

n = 173

n = 133

n = 126

n = 96

n = 74

n = 67

n = 63

n = 53

n = 43

n = 34

n = 28

n = 19

n = 6

55

Improving Adherence to Opioid Therapy

▪ A good patient-doctor relationship

▪ Defined treatment objectives

▪ Tools for disease prognosis

▪ Simple treatment regimens

▪ Identification of high risk for AEs or drug abuse

▪ AE management

▪ Monitoring treatment success

▪ Antidepressant management

▪ Community support

▪ Education for patients and caregivers

Graziottin, et al. Pain Practice. 201;574-581.

56

Physician-Patient Communication

Among those who felt uncomfortable talking about OIC with their HCP, reasons cited included“previously discussed in an earlier visit” (32%) and “I feel embarrassed” (68%).

71

90

49

80

29

10

51

20

Has your doctor discussed the side effectsof your pain medication when prescribing?

If yes, was OIC one of these?

Has your doctor discussed the subject ofOIC in follow up visits?

Do you feel comfortable talking about OICwith your HCP?

Yes No

Patients (%)


57

Assessing History of Constipation and Opioid Use: Asking the Right Questions

▪ Over the past 2 weeks, how many BMs were spontaneous?

▪ Ideally, how often would you like to have BMs?

▪ Since starting opioid medication, have you been experiencing constipation or worsening of current constipation?

▪ How long after did you begin experiencing constipation?

▪ In past 7 days, did you change how you used your opioid medication(s) so that you could have BMs?


58

▪ OIC is a frequent side effect of opioid treatment that negatively impacts patient QOL and can lead to poor adherence and inadequate pain management

▪ If left untreated, OIC may lead to the development of severe bowel dysfunction, increased surgical events, ED visits, and hospitalizations

▪ In addition to nonpharmacologic treatments and OTC laxatives, prescription medications are available that have shown good efficacy for the improvement of OIC symptoms with minimal side effects

▪ Patients receiving opioids should be routinely assessed for signs of constipation and risk for poor opioid adherence with the overall goal of minimizing OIC impact while ensuring adequate pain control

Summary

59

Questions and Answers

60

Thank You!

61

Chronic Pain Among Adults in the US

Available at: http://www.gallup.com/poll/154169/chronic-pain-rates-shoot-until-americans-reach-late-50s.aspx

62

Impact of Persistence and Bothersomeness of Pain on Health Status and Disability

Health status Disability

Nahin, et al. J Pain. 2015;16(8):769–780.

63

Differential µ-opioid Receptor Tolerance in the GI Tract

Nelson, et al. Ther Adv Chronic Dis. 2016;7(2) :121-134.

64

Impact on Workplace Productivity

Survey QuestionHours

(mean ± SD)

How many hours did you miss from work because of problems associated with your constipation?

6.2 (13.9)

How many hours did you miss from work because of any other reason?

1.6 (5.3)

How many hours did you actually work? 36.3 (13.7)

Coyne KS, et al. Clinicoecon Outcomes Res. 2014;6:269-281.

65

Lifestyle Modification for the Treatment of OIC

Chokhavatia, et al. Drugs Aging. 2016;33:557–574.

Intervention Mechanism of Action Potential Limitations in Elderly Patients

Dietary

• Increases stool weight/hydration

• Decreases colonic transit time

• Effectiveness of increased dietary fiber in OIC not established

• Poor response to dietary fiber ≥30 g/day in patients with slow-transit constipation and dyssynergic defecation

• Reluctance to increase fluid intake due to perceived risk of being incontinent

• May be ineffective in patients with chewing/swallowing disorders

• Failed to reduce laxative use or improve constipation in acute care setting

Physical Activity• Stimulates colonic activity

after exercise• Chronic pain may limit patient’s ability to engage in

physical activity

66

Effect of Naloxegol Treatment on Pain and Daily Opioid Use

Webster, et al. AAPM Annual Meeting Abstracts. 2016;219.

improving the diagnosis and management of opioid … constipation to optimize outcomes of patients...

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