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.
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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
Osteoarthritis: Improving Clinical Performance in Managing Pain and Mobility
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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
Zhang W, et al. Osteoarthritis Cartilage 2008;16:137-162.
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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)
Zhang W, et al. Osteoarthritis Cartilage 2008;16:137-162.
7. Don’t Forget About Non-Pharmacological Options
Weight reduction Range of motion exercises Muscle strengthening Heat Aquatic therapy Physical therapy Orthotics Walking aids
Zhang W, et al. Osteoarthritis Cartilage 2008;16:137-162.
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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
Zhang W, et al. Osteoarthritis Cartilage 2008;16:137-162.
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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www.cmeoutfitters.com
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
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