NSAIDs, Rheumatoid Arthritis, & Osteoarthritis: A Case Approach Bobo Tanner MD Rheumatology &...
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Transcript of NSAIDs, Rheumatoid Arthritis, & Osteoarthritis: A Case Approach Bobo Tanner MD Rheumatology &...
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NSAIDs, Rheumatoid Arthritis, & Osteoarthritis:
A Case Approach
Bobo Tanner MD
Rheumatology & Allergy
Monday Feb 19, 2007 VMS IV
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AGENDA
• Differentiate RA & OA
• Therapeutic Choices
• Case based examples
• Treat Early & Monitor
• Monitor for Benefit & Side Effects
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Case 165-year-old man: knee pain that began
insidiously about a year ago. No other rheumatic symptoms.
PMHx: PUD, ischemic heart dz, sulfa allergy
• What further questions should you ask?
• What are the pertinent physical findings?
• Which diagnostic studies are appropriate?
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Inflammatory vs. Mechanical RA
History & PE• AM stiffness >1 hr.• Symmetrical swelling,
tenderness: wrists, MCPs, PIPs
Labs• 45-85% +RF, +CCP Ab
ESR,C-RP, Hct
X-rays• JSN • erosions
OAHistory & PE• Worse pain w/activity• DIPs, 1st CMC,
wt.bearing jts.Labs• Medication monitoring CBC,BMP,UA
X-rays• Osteophytes, asymmetry,
sclerosis
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Therapeutic Options
RANSAIDsCorticosteroidsDMARDsBiologic DMARDsAlso:Joint InjectionsPT/OTSurgery SLESteroidsAnti-malarialImmunosuppressive
OAAnalgesics
NSAIDs
Also:
Joint injections
PT/OT
Surgery
Nutritional supplements
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Case 1: Radiographic Features• Asymmetric joint
space narrowing
• Marginal osteophytes
• Subchondral cysts
• Bony sclerosis
• Malalignment
• NAILS THE DIAGNOSIS
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OA: Risk Factors• Why did this patient develop
osteoarthritis?
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OA: Risk Factors (cont’d)• Age: 75% of persons over age 70 have OA
• Female sex
• Obesity
• Hereditary
• Trauma
• Neuromuscular dysfunction
• Metabolic disorders
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Case 1: Cause of Knee OA
• On further questioning, patient recalls a serious knee injury during high school football
• Therefore, posttraumatic OA is most likely diagnosis
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Pharmacologic Management of OA
• NSAIDs
• Non-opioid analgesics
• Topical agents
• Opioid analgesics
• Intra-articular agents
• Unconventional therapies
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NSAIDs
• Inhibit prostaglandin synthesis & other• Account for ½ the Rx in the elderly• If no response to one may respond to
another• Lower doses may be effective• Do not retard disease progression
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NSAIDs (cont’d)
• Side effects: GI, renal, cardiac, edema
• Severe side effects <5%, but large numbers of users
• Gastroprotection increases expense
• Antiplatelet effects may be hazardous
• GI tolerance much better with COX-2
• C-V events overshadow COX-2
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Non-opioid Analgesic Therapy• Acetaminophen
• Pain relief comparable to NSAIDs, less toxicity
• Beware of toxicity from use of multiple acetaminophen-containing products
• Maximum safe dose = 4 grams/day• Lifetime dose & toxicity?
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* P<.05
Bradley, et al. N Engl J Med. 1991;325:87–91.
Ibuprofen vs Acetaminophen for
Knee OA—Equivalent Benefit
0 0.2 0.4 0.6 0.8
HAQ Pain
Walking Pain
Rest Pain*
50 Ft Walk
HAQ Disability
Change in Score
2400 Ibuprofen1200 IbuprofenAcetaminophen
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Celecoxcib vs Acetaminophen for Hip & Knee OA—Pincus data
PACES trial
Patient preferences:
• 53% celecoxib (200mg) vs
24% acetaminophen(4 gm) PACES-a (p<0.001)
• 37% acetaminophen v
28% placebo in PACES-a (p = 0.340)
Ann Rheum Dis. 2004 Aug;63(8):931-9
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OA: Nutritional Supplements
• Polysulfated glycosaminoglycans—nutriceuticals • Glucosamine +/- chondroitin sulfate:
Symptomatic benefit, no known side effects, long-term controlled trials pending
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Knee Injection
• Knee fully extended
• Junction upper third and lower two thirds of the patella
• Insert needle under patella and aim superiorly
© ACR
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OA: Intra-articular Therapy• Intra-articular
steroids• Pain relief • Up to q 3 mo• Risks: infection,
worsening diabetes, or CHF
• Joint lavage• Symptomatic benefit
demonstrated
• Hyaluronate injections*• Synvisc ® , Hylgan®• Symptomatic relief • Improved function• $$$$$$$• Series of injections, fail
steroids first?• No evidence of long-
term benefit• Knees, other?
* Altman, et al. J Rheumatol. 1998;25:2203.
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Strengthening Exercise for OA• Decreases pain and increases function• Physical training rather than passive therapy• General program for muscle strengthening
• Warm-up with ROM stretching• Step 1: Lift the body part against gravity, begin
with 6 to 10 repetitions• Step 2: Progressively increase resistance with
free weights or elastic bands• Cool-down with ROM stretching
Rogind, et al. Arch Phys Med Rehabil. 1998;79:1421–1427.Jette, et al. Am J Public Health. 1999;89:66–72.
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Surgical Therapy for OA• Arthroscopy
• May reveal unsuspected focal abnormalities
• Results in tidal lavage• Expensive, complications possible
• Osteotomy: May delay need for TKR for 2 to 3 years
• Total joint replacement: for severe pain and function significantly limited
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Case 2: Rheumatoid Arthritis• 53-year-old woman with 6 months history
of RA sx
• Morning stiffness = 30 minutes
• Synovitis: 1+ swelling of MCP, PIP, wrist, and MTP joints
• Normal joint alignment
• Rheumatoid factor positive, anti-CCP +
• No erosions seen on x-rays
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Rheumatoid Arthritis: Treat Early &Prevent Damage & Dysfunction
• Ulnar deviation of R hand
• MCP & PIP swelling
• synovitis of left wrist
• Joint space narrowing & erosions on x-ray
• Synovial thickening feels like a firm sponge
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Case 2 (cont’d)• Assessment
• Rheumatoid Arthritis• No sign of damage
• Treatment• NSAID, steroid, DMARD • Education + ROM, conditioning, and
strengthening exercises
Which DMARD would you choose?
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Rheumatoid Arthritis: Drug Treatment Options
• NSAIDs – Symptomatic relief, improved function– No change in disease progression
• Low-dose prednisone (10 mg qd) – If used long term, consider prophylactic treatment for
osteoporosis
• Intra-articular steroids – Useful for flares
Paget. Primer on Rheum Dis. 11th edition. 1997:168.
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Rheumatoid Arthritis: • Disease modifying drugs (DMARDs)
– Hydroxychloroquine (Plaquenil®)• Modest effect, low toxicity
– Sulfasalazine• Moderate effect, monitor like MTX
– Methotrexate• Most effective single DMARD• Good benefit-to-risk ratio
– Leflunomide (Arava®)• Effect & side effects similar to MTX
• Combinations
Alarcon. Rheum Dis Clin North Am. 1998;24:489–499.Paget. Primer on Rheum Dis. 11th edition. 1997:168.
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Rheumatoid Arthritis: Monitoring Treatment With DMARDs
• These drugs need frequent monitoring
• Blood, liver, lung, kidney,skin are frequent sites of adverse effects
• √ CBC,LFTs, creatinine, urine
• Lab intervals: 4 to 12 weeks commonly
• Most patients need to be seen 3 to 6 times a year
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Biologic DMARDs
Anti-TNF – Etanercept (Enbrel®) 50mg SQ weekly– Infliximab (Remicade®) IV q 8 weeks– Adalimumab (Humira®) 40mg SQ QOW– Rapid onset, effective in refractory patients with
and w/o MTX, halts bone erosions– Screen for Tb, infections, expensive
Also– Anakinra (Kineret®), daily SQ, inj. anti-IL-1– Abatacept (Orencia®), IV monthly , T cell 2nd sig.– Rituximab ( Rituxan®) IV x 2, TNF failure, B cells
Fleischmann. Rheum Dis Clin North Am. 2006;32(1):21-28.
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Early Intervention Is Effective in RAEarly Intervention Is Effective in RA
• Several studies collectively provide clear evidence that delayed use of DMARD therapy in RA may adversely affect clinical and radiographic outcomes
• Treatment should be initiated within months of the diagnosis, not years
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Short Delay of Therapy Affected Joint Damage
Lard LR, et al.Lard LR, et al. Am J Med. Am J Med. 2001;111:446-451 2001;111:446-451..
Time (months)Time (months)
00
22
44
66
88
1010
1212
1414
00 66 1212 1818 2424
Early Treatment = median 15 daysEarly Treatment = median 15 days
Delayed Treatment = median 123 daysDelayed Treatment = median 123 days
JointJoint
DamageDamage
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Percentage improvement
Percentage deterioration
Ritchie articular index
Morning stiffness
Radiological score
VAS = 10 cm visual analogue scale.VAS = 10 cm visual analogue scale.
HemoglobinPain VAS
Grip strength
Sedimentation rate
75
50
25
0
–25
–50
–75
Mulherin D, et al. Br J Rheumatol. 1996;35:1263-1268.
Clinical Parameters Don’t Correlate with Bone Damage
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Case 2
• Which DMARD would you choose?
• Monitor :
Clinically
Labs
X-rays
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Case 3• 68-year-old woman, 3-years of RA ,
squeezed into your schedule as a new patient
• 4 weeks of increasing fatigue, dizziness, dyspnea, and anorexia
• Joint pain and stiffness: mild & unchanged
• Meds: flare up 4 mos. ago ,switched to naproxen and prednisone
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Case 3 (cont’d)• Past history: Peptic ulcer 10 years ago,
mild hypertension
• Exam: thin, pale apathetic woman with Temp 98.4ºF, BP 110/65, pulse 110 bpm
• Symmetrical 1+ synovitis of the wrist, MCP, PIP, and MTP joints
• Heart, lungs, and abdomen: unremarkable
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Case 3 (cont’d)• The doctor is falling behind in the schedule
• What system must you inquire more about today?A. Cardiovascular
B. Neuropsychological
C. Endocrine
D. Gastrointestinal
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Case 3 (cont’d)
• Clues of impending disaster• High risk for NSAID gastropathy• Presentation suggestive of blood loss
• Pale, dizzy, weak• Tachycardia, low blood pressure
• No evidence of flare in RA to explain recent symptoms of increased fatigue
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Case 3 (cont’d)
• NSAID gastropathy is sneaky and can be fatal
Don’t Miss It
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Singh. Am J Med. 1998;105(suppl B):31S–38S.
NSAID Gastropathy• Gastric ulcers are more common than
duodenal ulcers
• No reliable warning signs
• 80% of occur without prior symptoms
• Ulcers in RA 2.5- 5.5 times more than general population
• 107,000 hospitalized & 16,000 deaths annually due to NSAID-GI complications
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NSAID Gastropathy: Key Points
Know the risk factors• The best way to treat it is to prevent it
• Avoid it: Use acetaminophen, salsalate,
(or ? selective COX-2 inhibitor)• Counteract it: PPI or prostaglandin analogue
• Antacids and H2 blockers are not the answer• May mask symptoms but do not prevent
serious events
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Singh. Am J Med. 1998;105(suppl B):31S–38S.
GI Risk Factors : NSAID Ulcers
• Older age• Prior history of peptic ulcer or GI symptoms with
NSAIDs• Concomitant use of prednisone• NSAID dose• Disability level: The sicker the patient the higher
the risk
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Balancing NSAID Efficacy and Safety
• Is NSAID therapy indicated?
• Can low dose relieve symptoms?
• Risk of complications ?
• Consider NSAID therapy with reduced GI toxicity or combination Rx with GI med
• Antiinflammatory activity
• Analgesia
• GI toxicity• Renal toxicity• Platelet effects
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Selective COX-2 Medications
• VIOXX® :withdrawn from market 9/30/04
• Celebrex®
• Bextra® withdrawn 2005
also associated with cardiovascular dz, hypertension, edema and sulfa & skin rxns
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COX-2 Selective NSAIDs• A replacement for non-selective NSAIDs?
• Pain relief equivalent to older NSAIDs• Less GI toxicity (rofecoxcib)• No effect on platelet aggregation or bleeding
time• Cost similar to generic NSAIDs plus proton
pump inhibitor or misoprostol• Side effects: Cardio-Vascular,BP,edema
Medical Letter. 1999;41:11–12.
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COX-2 : CV events (rofecoxcib)
3.75 3.75
7.5
15
0
2
4
6
8
10
12
14
16
Events/ 1000 pts.
<18 months >18 months
VIOXX Polyp Trial
placebo
VIOXX
Time in studyWSJ 10/1/04
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Case 4• 52-year-old man with destructive RA
• Rx NSAID & low-dose prednisone
• MTX & Remicade( anti-TNF) started 4 months ago
• 3-week history of fever, dry cough, and increasing shortness of breath
• Exam: Low-grade fever, fine rales in both lungs,• Labs: normal CBC ,LFTs, low alb• Chest xray: bilat.interstitial infiltrates
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Case 4 (cont’d)
• What should be done?
A. Culture, treat with antibiotic for bacterial pneumonia
B. Place PPD, sputum for AFB
C. Give steroids for hypersensitivity pneumonitis and stop methotrexate
D. Give a high-dose steroids and increase methotrexate for rheumatoid lung
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DMARDs & Biologics Have a Dark Side
Don’t Miss It
Methotrexate may cause serious problems
LungLiverBone marrow
Anti-TNF (Remicade, Enbrel, Humira) assoc. with TB reactivation and other infections
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Case 5• A pre-op physical has been ordered for a
routine cholecystectomy on a 43-year-old woman with RA since age 20
• PMH: bilateral THR ,left TKR
• Meds: NSAID, 5 mg/d prednisone, MTX• General physical exam normal• MS exam, extensive deformities, mild synovitis• In addition to routine tests, what test should be ordered
before surgery?
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Don’t Miss It
Subluxation of C1 on C2
RA can cause asymptomatic instability of the neckManipulation under anesthesia can cause spinal cord injury
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Clues for C1-C2 Subluxation• Long-standing rheumatoid arthritis or JRA• May have NO symptoms• C2-C3 radicular pain in the neck and occiput• Spinal cord compression
• Quadriparesis or paraparesis• Sphincter dysfunction • Sensory deficits• TIAs secondary to compromise of the vertebral arteries
Anderson. Primer on Rheum Dis. 11th edition. 1997:161.
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Summary
• Distinguish Inflammatory Disease (RA) from mechanical (OA)
• Treat RA early
• Know the medication side effects
• Know the complications of the disease
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One Last Word:Unconventional Therapies
• Keep in touch with current information. The unconventional may become conventional• www.quackwatch.com• ACR Website
(www.rheumatology.org)• Arthritis Foundation Website
(www.arthritis.org)