Osteoarthritis: Improving Clinical Performance in Managing ...s3.amazonaws.com/zanran_storage/ · Osteoarthritis: Improving Clinical Performance in Managing Pain and Mobility 2 INFORMATION

Osteoarthritis: Improving Clinical Performance in Managing Pain and Mobility

A Free, One-Hour CME/AAFP WEBCAST Activity Based Off of a Live Symposium Held During the GAFP 2010 Annual Scientific Assembly and Exhibition

www.cmeoutfitters.com/CM524(free account activation and log-in required)

FACULTY: Byron L. Cryer, MD

University of Texas Southwestern Medical SchoolDallas, TX

Gary Ruoff, MDWestside Family Medical Center

Michigan State University-KalamazooKalamazoo, MI

This continuing education activity is provided by

CME Outfitters, LLC, gratefully acknowledges an educational grant from AstraZeneca Pharmaceuticals in support of this CE activity and an unrestricted educational grant from Mallinckrodt, a Covidien company.

MMV-028-122210-90

SYLLABUS AND COURSE GUIDERelease Date: December 22, 2010 Credit Expiration Date: December 22, 2011

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INFORMATION FOR PARTICIPANTSStatement of NeedA progressive, osteodegenerative condition, osteoarthritis (OA) is a major cause of skeletal pain and chronic disability. The pain of OA often makes the mechanics of mobility (e.g., walking and climbing stairs) difficult or virtually impossible, thus impairing quality of life in patients. Further, it is the most common reason for adult hip and knee replacement.

There are a variety of pharmacological and nonpharmacological treatment modalities for OA, yet no modality is universally effective. This unmet need is underscored by results of a treatment satisfaction survey in which 73% of 2,000 primary care physicians and 63% of 30,000 patients reported inadequate pain relief with current treatment regimens.1

Many patients’ pain can be controlled with acetaminophen, but if pain persists, oral NSAIDs (in the form of a traditional agent or a COX-2 inhibitor) may be a necessary next step in managing joint pain. It is well recognized that traditional NSAIDs and COX-2 inhibitors are associated with gastrointestinal (GI) side effects and can lead to life-threatening complications. Evidence-based guidelines recommend coadministration of NSAIDs with a proton pump inhibitor (PPI) or misoprostol, yet few who are at risk for upper GI complications receive preventive, gastroprotective agents.2

This webcast presents expert faculty who will address both pharmacological and nonpharmacological treatment options that integrate strategies to minimize risk and improve outcomes for patients with OA.1 Crichton B, Green M. GP and patient perspectives on treatment with non-steroidal anti-inflammatory drugs for the treatment of pain in osteoarthritis. Curr Med Res Opin 2002;18:92-96. 2 Goldstein JL, Howard KB, Walton SM, McLaughlin TP, Kruzikas DT. Impact of adherence to concomitant gastroprotective therapy on nonsteroidal-related gastroduodenal ulcer

complications. Clin Gastroenterol Hepatol 2006;4:1337-1345.

Activity GoalTo improve physician competence in the awareness and application of validated guidelines in the management of osteoarthritis.

Learning ObjectivesAt the end of this CE activity, participants should be able to:

• Develop multimodal OA pain treatment strategies that are based on best-available clinical evidence and individualized to the patient.

• Document evidence that you assessed for gastrointestinal and cardiovascular risk factors in patients with OA pain in whom you are considering prescribing an NSAID.

• In patients taking an NSAID to control OA pain, recommend GI protective strategies to appropriate candidates.

Target AudienceFamily practice physicians, primary care physicians, and other healthcare professionals with an interest in managing patients with osteoarthritis.

Financial SupportCME Outfi tters, LLC, gratefully acknowledges an educational grant from AstraZeneca Pharmaceuticals in support of this CE activity and an unrestricted educational grant from Mallinckrodt, a Covidien company.

CREDIT INFORMATIONCME Credit (Physicians)CME Outfitters, LLC is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

CME Outfitters, LLC designates this enduring material for a maximum of 1.0 AMA PRA Category 1 Credit™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Note to Physician Assistants: AAPA accepts Category I credit from AOACCME, Prescribed credit from AAFP, and AMA Category I CME credit for the PRA from organizations accredited by ACCME.


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AAFP Credit (Family Physicians)This activity, Osteoarthritis: Improving Clinical Performance in Managing Pain and Mobility, has been reviewed and is acceptable for up to 1 Prescribed credit(s) by the American Academy of Family Physicians. AAFP accreditation begins December 15, 2010. Term of approval is for one year(s) from this date, with option for yearly renewal.

AMA/AAFP Equivalency: AAFP Prescribed credit is accepted by the American Medical Association as equivalent to AMA PRA Category 1 Credit™ toward the AMA Physician’s Recognition Award. When applying for the AMA PRA, Prescribed credit earned must be reported as Prescribed, not as Category 1.

All other clinicians will either receive a CME Attendance Certificate or may choose any of the types of CE credit being offered.

CREDIT REQUIREMENTSSuccessful completion of this CE activity includes participating in the live or recorded activity, reviewing the course materials, and following the instructions below within 30 days of completion of the activity:

To complete your credit request form, activity evaluation, and post-test online, and print your certificate or statement of credit immediately (70% pass rate required), please visit www.cmeoutfitters.com/test (requires free account activation).

There is no fee for participation in this activity. The estimated time for completion is 60 minutes.Questions? Please call 877.CME.PROS.

FACULTY BIOS & DISCLOSURESByron L. Cryer, MDDr. Cryer is the John C. Vanatta Professor of Medicine in the Department of Internal Medicine, Division of Digestive and Liver Diseases and an Associate Dean at the University of Texas Southwestern Medical Center. Dr. Cryer is certified in Internal Medicine with a subspecialty in Gastroenterology. His clinical interests are in general gastroenterology, specifically, acid-peptic diseases of the upper gastrointestinal tract.

Dr. Cryer is a graduate of Harvard University in Cambridge, Massachusetts. He received his medical degree in 1986 from Baylor College of Medicine in Houston, Texas, where he also completed his internal medicine residency training. Dr. Cryer completed his gastroenterology fellowship training at the University of Texas Southwestern Medical Center in 1992.

Dr. Cryer is a member of the American Gastroenterological Association and former Associate Chair of the Esophagus, Stomach, and Duodenum section of the American Gastroenterological Association. Dr. Cryer’s primary research has been in the pathogenesis of peptic ulcer disease. His research focus has been clinically oriented in that he has exclusively studied the pathophysiology of these processes in humans. Dr. Cryer’s recent investigations have explored the mechanism of gastrointestinal toxicity of nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, clopidogrel within the stomach and duodenum, mechanisms of other drug induced injury within the upper GI tract and Helicobacter pylori.

Gary Ruoff, MD Dr. Ruoff earned his medical degree from the Stritch School of Medicine, Loyola University, Chicago, Illinois, and presently serves as Director of Clinical Research at the Westside Family Medical Center in Kalamazoo, Michigan. He is also Clinical Professor of Family Practice at Michigan State University College of Medicine in East Lansing. Dr. Ruoff’s main research interest is pain therapy and management, including headache and acute and chronic pain arising from the musculoskeletal and neurogenic systems. Dr. Ruoff is actively involved in teaching students, residents and physicians, and serves on several advisory boards for pain and pain therapy. He has authored over 80 articles, abstracts and monographs, and received numerous awards for his research work.


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Disclosure DeclarationIt is the policy of CME Outfitters, LLC, to ensure independence, balance, objectivity, and scientific rigor and integrity in all its CE activities. Faculty must disclose to the participants any significant relationships with commercial companies whose products or devices may be mentioned in faculty presentations, or with the commercial supporter of this CE activity. CME Outfitters, LLC, has evaluated, identified, and attempted to resolve any potential conflicts of interest through a rigorous content validation procedure, use of evidence-based data/ research, and a multidisciplinary peer review process. The following information is for participant information only. It is not assumed that these relationships will have a negative impact on the presentations.

Dr. Cryer has disclosed that he receives research/grants from PLx Pharma. He serves as a consultant to AstraZeneca Pharmaceuticals LP, Horizon Therapeutics, Inc., NicOx, Inc., Pfizer Inc., PLx Pharma, and Sucampo Pharmaceuticals, Inc.

Dr. Ruoff has no disclosures to report.

Jeffrey Helfand, DO, MS (peer/content reviewer) has no disclosures to report.

Unlabeled Use DisclosureFaculty of this CME activity may include discussions of products or devices that are not currently labeled for use by the FDA. The faculty have been informed of their responsibility to disclose to the audience if they will be discussing off-label or investigational uses (any uses not approved by the FDA) of products or devices.

CME Outfitters, LLC, the faculty, AstraZeneca Pharmaceuticals, and Mallinckrodt, a Covidien company, do not endorse the use of any product outside of the FDA labeled indications. Medical professionals should not utilize the procedures, products, or diagnosis techniques discussed during this activity without evaluation of their patient for contraindications or dangers of use.

Activity SlidesThe slides that are presented in this activity are available for download and printout at the CME Outfitters website:www.cmeoutfitters.com. Activity slides may also be obtained via fax or email by calling 877.CME.PROS.


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Abbreviation List

BMI Body mass index

COX-2 Cyclooxygenase-II

Coxib Cyclooxygenase inhibitor

CV Cardiovascular

EULAR European League Against Rheumatism

GI Gastrointestinal

GPA Gastroprotective agent

H2RA Histamine2-receptor antagonist

MSM Methylsulfonylmethane

MUCOSA Misoprostol Ulcer Complications Outcomes Safety Assessment

NO-NSAID Nitric oxide-donating non-steroidal anti-inflammatory drug

NSAID Non-steroidal anti-inflammatory drug

OA Osteoarthritis

PC-NSAID Phosphatidylcholine-associated non-steroidal anti-inflammatory drug

PPI Proton-pump inhibitor

PUBs Perforations, ulcers and bleeds

RCT Randomized, controlled trial

ROM Range of motion

SAMe S-adenosylmethionine

TENS Transcutaneous electrical nerve stimulation

TID Three times daily

UGI Upper gastrointestinal

UK United Kingdom

US United States

VAS Visual Analogue Scale

VIGOR Vioxx Gastrointestinal Outcomes Research


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Multi-Modal Treatment Strategies

for Patients with Osteoarthritis Gary Ruoff, MD

Westside Family Medical Center Michigan State University-Kalamazoo

Gary Ruoff, MD Disclosures

Research/Grants: None

Speakers Bureau: None

Consultant: None

Stockholder: None

Other Financial Interest: None

Advisory Board: None

Pathophysiology of OA Most commonly affects hands and weight-bearing joints Involves all joint tissue – cartilage, bone, synovium, ligaments, muscle Process is both biochemical and biomechanical Emerging evidence suggests symptoms and disease progression related to inflammation

Atlman R, Ruoff G, et al. J Family Practice 2009;58:1-9.

Osteoarthritis: Improving Clinical Performance in Managing Pain

and Mobility Byron L. Cryer, MD

Gary Ruoff, MD


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10. When OA is Suspected, Accurately Identify the Affected Joint

Comprehensive examination should include:1

Joint pain on manipulation Muscle strength and ligament stability Body weight and BMI Postural alignment during standing and walking

Typically, x-rays provide little information for initial diagnosis

40% of patients with radiographic evidence of OA are asymptomatic2

1. Atlman RD, Ruoff G, et al. J Family Practice 2009;58:1-9. 2. Altman RD. Semin Arthritis Rheum 1991;20:40-47.

9. Select Therapy-Based Pain Characteristics

Weight-bearing joint Weight reduction Exercise Lifestyle modification Medication

Non-weight-bearing joint Medication Splints Heat

8. Do Therapy Trials in a Systematic Fashion

Start with acetaminophen Use NSAIDs at the lowest possible dose for shortest possible duration Choose NSAID based on safety profile Topical NSAIDs (diclofenac gel) and capsaicin can be effective adjuncts Intra-articular injections with corticosteroids can be used in patients with moderate to severe pain not responding to oral analgesics/anti-inflammatory agents

Zhang W, et al. Osteoarthritis Cartilage 2008;16:137-162.

Treatment Goals for OA Reduction of joint pain and stiffness

Maintain and improve joint mobility

Reduce physical disability and handicap

Improve health-related quality of life

Limit progression of joint damage

Educate patients about the nature of the disorder and long-term management



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6. Patient Education Important Aspect of Long-Term Strategy

Lifestyle modification

Pain management

Side effects Take medication as prescribed Take with food – full meal Co-administration with PPI

5. Use of Weak Opioids Can Be Considered for Refractory Pain

Evidence that opioids have demonstrated efficacy in OA pain

18 placebo-controlled RCTs with 3,244 patients showed a moderate effect size for reduction in pain intensity

13-18 weeks Pooled effect sizes for opioids vs. placebo were -0.79 and -0.31 respectively Long-term safety in OA not determined

Avouac J, et al. Osteoarthritis Cartilage 2007;15:957-965.

4. What If Oral Medications Don’t Manage Pain?

Intra-articular corticosteroid injections

Intra-articular injections of hyaluronic acid

Knee/hip replacement

Joint fusion

Transcutaneous electrical nerve stimulation (TENS)


7. Don’t Forget About Non-Pharmacological Options

Weight reduction Range of motion exercises Muscle strengthening Heat Aquatic therapy Physical therapy Orthotics Walking aids



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Differences in Pain Intensity Measured on Visual Analogue Scale (VAS) Between Experimental

Interventions and Placebo Over Time

-5 -4 -3 -2 -1 0 1 2 3 4 5

0 3 6 9 12 15 18 21 24

Chondroitin Glucosamine Combination

Diff

eren

ce in

mea

ns o

n 10

cm

VA

S

Sup

plem

ent

supe

rior

Clin

ical

eq

uiva

lenc

e P

lace

bo

supe

rior

Months

Wandel S, et al. Br Med J 2010;341:bmj.c4675.

No. of 10 7 6 4 3 3 3 3 5 trials No. of 3786 2009 2828 1353 1046 1046 1046 1046 1558 patients

2. When Prescribing NSAIDs, Perform a GI and CV Risk Assessment

NSAIDs can cause serious GI complications such as peptic ulcer, perforations, and bleeds (PUBS)1

Risk increases with age, concurrent use of other medications, and probably duration of use

EULAR advises: COX-2 and NSAIDs are contraindicated in patients with ischemic heart disease or stroke2

Caution in patients with risk factors for heart disease – hypertension, hyperlipidemia, diabetes, smoking2

1. Tramer MR, et al. Pain 2000;85:169-182. 2. Zhang W, et al. Osteoarthritis Cartilage 2008;16:137-162.

1. Always Carefully Consider Implementing a Gastroprotection Strategy in Patients with OA on NSAIDs

Use of misoprostol or a proton pump inhibitor (PPI) for gastroprotection is recommended


3. Know What Medications/Supplements Your Patients May Be Reading About

Drug-drug interactions related to: Nutritional supplements

Glucosamine Chondroitin

Alternative/herbal medicines SAMe (S-adenosylmethionine) MSM (methylsulfonylmethane)

Flavocoxid Marketed as a medical food for the management of OA

Atlman R, Ruoff G, et al. J Family Practice 2009;58:1-9.


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Byron L. Cryer, MD Disclosures

Research/Grants: PLx Pharma Speakers Bureau: None Consultant: AstraZeneca Pharmaceuticals LP; Horizon Therapeutics, Inc.; NicOx, Inc.; Pfizer Inc.; PLx Pharma; Sucampo Pharmaceuticals, Inc. Stockholder: None Other Financial Interest: None Advisory Board: None

Incidence and Prevalence of NSAID-Associated GI Complications

More than 60 million Americans are NSAID users1

1% to 2% of users have clinically significant upper GI events

Endoscopic studies indicate that gastric or duodenal ulcers develop in approximately 15% to 30% of patients using NSAIDs2

Estimates of mortality vary widely from 3,200 to higher than 16,500 deaths per year in the United States1

1. Cryer B. Am J Gastroenterol 2005;100:1694-1695. 2. Laine L. Gastroenterology 2001;120:594-606.

.

Dyspepsia occurs in 25% to 50% of patients

with or without complications

Complications 1% to 2%

Ulcers 15% to

30%

No Lesion 70% to 85%

Gastrointestinal Side Effects Induced by Nonselective NSAIDs

Graham DY, et al. Ann Intern Med 1993;119:257-262. Langman MJ, et al. Lancet 1994;343:1075-1078. Larkai EN, et al. J Clin Gastroenterol 1989;11:158-162. Silverstein FE, et al. Ann Intern Med 1995;123:241-249.

Assessing Risk When Making Treatment Choices for Patients

with Osteoarthritis Byron L. Cryer, MD

University of Texas Southwestern Medical School

Dallas VA Medical Center


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NSAIDs

1990 2005 Cause of Peptic Ulcers

53% 20-30%

47% 70-80% H. pylori

Peptic Ulcer Disease and NSAIDs

Ramsoekh D, et al. Clin Gastroenterol Hepatol 2005;3:859-864.

The major cause of peptic ulcer disease in Amsterdam has changed from H. pylori to NSAIDs

Risk Factors for Serious GI Adverse Events with NSAIDs

1. García-Rodriguez LA. Lancet 1994;343:769-772. 2. Shorr RI. Arch Intern Med 1993;153:1665-1670. 3. Piper JM, et al. Ann Intern Med 1991;114:735-740. 4. Gutthann SP, et al. Epidemiology 1997;8:18-24.

Anticoag/NSAID Use

1 5 10 15

4.4 (2.0-9.7)3

12.7 (6.3-25.7)2

2.9 (2.2-3.8)4

5.8 (4.0-8.6)4

5.6 (4.6-6.9)1

3.1 (2.5-3.7)1

1.6 (1.4-2.0)1

13.5 (10.3-17.7)1

Corticosteroid Use

Low-Dose NSAID

High-Dose NSAID

Age 70-80

Age 60-69

Age 50-59

Prior Bleed

Relative Risk

Risk for GI Complications Begins at an Earlier Age in Men

Adapted from Lanas A, et al. Am J Gastroenterol 2005;100:1685-1693.

0.7 0.5 0.5 0.4

1 1.5

1.8 2.5

3 3.5

4.6 4.5

5 6.9

7.7 7.8

5.6 5

0 1 2 3 4 5 6 7 8 9

35-39

45-49

55-59

65-69

75-79

> 84 80-84

70-74

60-64

50-54

40-44

30-34 25-29 20-24 15-19 10-14

5-9 0-4

Age

(Yea

rs)

Patients with GI Complications (%)

Females Males

*

* Male patients had an onset of GI complications at an earlier age than women

0.6 0.5 0.5 0.3 0.3 0.4 0.5

1 1.3

1.8 2.2

3.1 4.5

6 5.8

7.4

0.6 0.8

1 2 3 4 5 6 7 8 9

Mortality Associated with NSAID/Aspirin Use

Lanas A, et al. Am J Gastroenterol 2005;100:1685-1693.

Mor

talit

y R

ate

per M

illio

n P

eopl

e

US UK Spain 0

50 100 150 200 250 300 350 400 450 500

153

253

443


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The Risk of NSAID-Associated Upper GI Complications is Constant Over Time

1. Silverstein FE, et al. Ann Intern Med 1995;123:241-249. 2. Bombardier C, et al. N Engl J Med 2000;343:1520-1528.

0 30 60 90 120 150 180 Pro

babi

lity

of U

GI C

ompl

icat

ion

MUCOSA Trial1

NSAIDs (N = 4,439)

Cum

ulat

ive

Inci

denc

e (%

)

4.0

2.5

5.0 4.5

3.5 3.0

2.0 1.5 1.0 0.5

0

VIGOR Trial2

Naproxen (N = 4,029) 0.012

0

0.003

0.006

0.009

0 2 4 6 8 10 12 Months of Follow-Up Days on Study

Rel

ativ

e R

isk

GI Safety Profiles of Available Agents Relative Risk: Current Use vs. Nonuse

* Statistical significance was not reported García-Rodríguez LA, et al. Epidemiology 2001;12:570-576. Hernández-Díaz S, et al. Arch Intern Med 2000;160:2093-2099. de Abajo FJ, et al. BMC Clin Pharmacol 2001;1:1.

2.7 3.4

3.8 4.0 4.1 4.6 4.6

6.3

1.1 1.3

2.2

3.6

1.9

3.4 3.3

4.6

2.2

1 1

2

3

4

5

6

7 NSAID risk varies Aspirin and ibuprofen have higher risk than non-NSAIDs*

Aspirin > Ibuprofen > Acetaminophen

Reducing the Risk

1

5.1 3.7 4.1

5.7

1

3

5

7

9

11

Nonuse 1-30 31-90 91-180 181-365

Days of NSAID Use

Rel

ativ

e R

isk

Increased risk appears at start of therapy and is maintained during use

High Risk of Upper GI Bleeding Is Maintained During NSAID Use

Hernández-Díaz S, et al. Arch Intern Med 2000;160:2093-2099.


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Options for Patients with GI Risk Who Need NSAIDs

NSAID plus gastroprotective agent Misoprostol PPI Histamine2-receptor antagonist (H2RA) — high dose

COX-2 inhibitor Non-NSAID pharmacologic therapy

Acetaminophen Tramadol Narcotics

Zhang W, et al. Osteoarthritis Cartilage 2008:16:137-162.

Relative GI Safety of Different Anti-Inflammatory Therapies: Overview

Therapy All nonselective NSAIDs Different formulations of nonselective NSAIDs Different routes of NSAID administration Gastroprotection co-therapy NSAIDs that specifically inhibit COX-2

Safety Profile Increased risk of serious GI events No reduction in serious GI toxicity No reduction in serious GI toxicity Reduction in serious GI toxicity but compliance issues Reduction in serious GI toxicity but possible increase in cardiovascular adverse effects

Gastroprotection Strategies

Use lowest effective NSAID dose

Misoprostol

Proton pump inhibitors

H2-receptor antagonists (high dose)

Zhang W, et al. Osteoarthritis Cartilage 2008:16:137-162.

Reducing the Risk of GI Complications with NSAIDs

Identify risk factors

Use of gastroprotective drugs

Safer NSAIDs


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Unmet Medical Needs in Improving GI Safety of OA

Treatments Problems with Adherence

Adherence to Evidence-Based Guidelines for Safe Prescription of NSAIDs in High-Risk* Patients

27.2

39.7 41.8

0

10

20

30

40

50

1 Risk Factor 2 Risk Factors 3 Risk Factors

N = 303,787 veterans prescribed NSAIDs in 2002 * Included age 65 years, concurrent corticosteroid or anticoagulant use, history of peptic ulcer, and high average daily dose of NSAIDs Abraham NS, et al. Gastroenterology. 2005;129:1171-1178.

Adh

eren

ce (%

)

2 GI Risk Factors 1 GI Risk Factor

86.6%

10.8% 2.5% 0.1%

81.2%

14.7% 4% 0.2%

COX-2 inhibitor alone NSAID + GPA

COX-2 inhibitor + GPA No gastroprotection

Utilization of Gastroprotective Strategies Among New NSAID Users

GPA = gastroprotective agent Sturkenboom MC, et al. Rheumatology 2003;42(Suppl 3):iii23-iii31.

0.17 (0.11-0.24) Misoprostol 800 μg

H2RA (standard dose)

0.42 (0.28-0.67)

0.73 (0.50-1.09)

0.40 (0.32-0.51)

0.50 0.25 1.0 0.75 1.25

Favors Co-Therapy

0.0

Misoprostol 400 μg PPI

Prevention of NSAID-Induced Ulcers Systematic Review of 41 RCTs

Rostom A, et al. Cochrane Database Systematic Review 2002;4.

H2RA (double dose) 0.44 (0.26-0.74)

Relative Risk vs. Placebo (95% Confidence Interval)

Favors Placebo

Intervention


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Potential New “Safer NSAIDs” Being Studied

Combination products PPI H2RA

NO-NSAIDs

PC-NSAIDs

Pro-drugs (e.g., naproxen)

Lipoxygenase/COX inhibitors

Recent Guidelines The Heart Is More Important

than the Stomach

Chan FKL, et al. Am J Gastroenterol 2008;103:2908-2918.

Nonadherence Is Associated with Decreased Relative Effectiveness

Goldstein JL, et al. Clin Gastroenterol Hepatol 2006;4:1337-1345.

Annualized rates of upper GI events per patient-year

R2 = 0.3088

0.0

0.1

0.2

0.3

0.4

0 20 40 60 80 100 Adherence (%)


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Summary PPIs, high-dose H2RA, misoprostol, and COX-2 selective inhibitors decrease upper GI ulcers due to traditional, nonselective NSAIDs (RCT evidence) Fixed-dose combination therapy may increase patient compliance with GI risk reduction strategies Patients with the highest GI risk may require more than one risk-reducing strategy such as COX-2 selective inhibitor plus a PPI Clinicians must balance GI and CV issues when choosing NSAID therapy

RCT = randomized controlled trial

Patient Case Vignette 61-year-old Obese Woman with Right

Knee Pain

Patient History 61-year-old obese woman presents to family physician with right knee pain

Weight: 225 lbs Height: 5’6” BMI: 34 kg/m2

Right knee pain has lasted 2 months, but has intensified over past 2 weeks necessitating the visit

Chan FKL, et al. Am J Gastroenterol 2008;103:2908-2918.

A patient requires regular NSAID treatment

Assessment of CV risk

High

Naproxen is preferred

Assessment of GI risk

High*

Avoid NSAIDs Naproxen + PPI/

misoprostol if NSAID is necessary

Average

Naproxen if not on aspirin

Naproxen + PPI/misoprostol if on

aspirin

Average

Any NSAIDs

Assessment of GI risk

High*

Nonselective NSAID + PPI/misoprostol

or Coxib + PPI/misoprostol**

Average

Nonselective NSAID alone*


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Treatment Plan Diagnosis: OA of the right knee History of ulcer at 25 years old so initiate acetaminophen 500 mg/day TID Recommend non-pharmacological interventions

Weight reduction Heat Exercise

Follow-Up Visit 3 Months Later

No change in weight or BMI

No improvement with acetaminophen

Continued decreased flexion and extension of right knee

Pain mostly unchanged, measured at 8 of 10

Clinical Considerations

GI history If prescribe NSAID, should you also prescribe a proton pump inhibitor (PPI)? Educate patient about importance of taking NSAID with food

Needed weight loss Counsel patient that little as 10 lb reduction in weight can improve pain scores

Physical Examination Range of motion (ROM) exam

Assess for ROM at hip and knees Decreased internal and external rotation of the hip Reduced flexion and extension Slight swelling of right knee No evidence of joint swelling in hands or feet Self-reported pain 9 out of 10


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Follow-Up Visit 3 Months Later

Weight reduced 15 lbs to 210 lbs

BMI reduced to 32 kg/m2

ROM remains limited

Pain score reduced to 6 of 10

What Next?


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Bibliography

Strategies for Treatment Selection in Patients with OA – Gary Ruoff, MD

Altman RD. Classification of disease: osteoarthritis. Semin Arthritis Rheum 1991;20(Suppl 2):40-47.

Atlman R, Kuritzky L, Ruoff G. Improving long-term management of osteoarthritis: strategies for primary care physicians. J Family Practice 2009;58(Suppl):S17-S24.

Avouac J, Gossec L, Dougados M. Efficacy and safety of opioids for osteoarthritis: a meta-analysis of randomized controlled trials. Osteoarthritis Cartilage 2007;15:957-965.

Tramer MR, Moore RA, Reynolds DJ, McQuay HJ. Quantitative estimation of rare adverse events which follow a biological progression: a new model applied to chronic NSAID sue. Pain 2000;85:169-182.

Wandel S, Juni P, Tendal B, et al. Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis. BMJ 2010;341:c4675.

Zhang W, Moskowitz RW, Nuki G, et al. OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage 2008;16:137-162.


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Bibliography

Assessing Risk When Making Treatment Choices for Patients with Osteoarthritis – Byron L. Cryer, MD

Abraham NS, El-Serag HB, Johnson ML, et al. National adherence to evidence-based guidelines for the prescription of nonsteroidal anti-inflammatory drugs. Gastroenterology 2005;129:1171-1178.

Bombardier C, Laine L, Reicin A, et al.; VIGOR Study Group. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med 2000;343:1520-1528.

Chan FK, Abraham NS, Scheiman JM, Laine L; First International Working Party on Gastrointestinal and Cardiovascular Effects of Nonsteroidal Anti-inflammatory Drugs and Anti-platelet Agents. Management of patients on nonsteroidal anti-inflammatory drugs: a clinical practice recommendation from the First International Working Party on Gastrointestinal and Cardiovascular Effects of Nonsteroidal Anti-inflammatory Drugs and Anti-platelet Agents. Am J Gastroenterol 2008;103:2908-2918.

Cryer B. NSAID-associated deaths: the rise and fall of NSAID-associated GI mortality. Am J Gastroenterol 2005;100:1694-1695.

de Abajo FJ, García Rodríguez LA. Risk of upper gastrointestinal bleeding and perforation associated with low-dose aspirin as plain and enteric-coated formulations. BMC Clin Pharmacol 2001;1:1.

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