OA Part 2 Flashcards
Overview of Pharmacologic
Treatment
Oral Medications
● Acetaminophen
● NSAIDS & COX-2 Inhibitors
● Glucosamine & Chondroitin
● Opioid analgesics
● Antidepressants
● Natural Health Products
- Topical Therapies
● Topical NSAIDs
● Capsaicin and other topical
rubefacients - Intra-articular Injections
● Corticosteroids
● Viscosupplementation /
Hyaluronic Acid
Acetaminophen
- Often first line drug therapy for OA
- Adequate Trial
● Trial drug 2-3 wks at doses not exceeding 4g/day.
● Consider limiting to ≤ 3250mg/day in older adults
● Dose regularly around-the-clock, not PRN. - Well tolerated & “safe” drug
- Liver Toxicity
● Numerous reports of liver damage & death
● Can be avoided by:
● Following dosing recommendations
● Avoid other preparations containing acetaminophen
● Avoiding use in hepatic dysfunction
● Limiting dose (2-3 g/day) & duration in chronic alcohol users
and others at increased risk
the evidence for improvement tends to be fairly small. But You can see here that that patients who looking at disability in particular, if they’re receiving it for less than two weeks, there’s really, the evidence suggests no benefit. Where the benefit exists if patients are taking it for greater than two weeks to less than three months. So again, patients who are using acetaminophen, a fair trial of it would be to take it for at least two weeks, but preferably for perhaps a month. So two to three weeks would be would be ideal to see if they’re going to benefit from it or not.
Less effective than NSAIDs
Acetaminophen - Evidence
Associated with small improvements in pain and
disability in patients with knee or hip OA
● SR of 10 RCTs (vs placebo) 🡪 3,541 patients
● ↓ pain at ≤ 2 weeks (WMD -3.3, 95% CI -5.8 to -0.8)
● ↓ pain from > 2 weeks to ≤ 3 months (WMD -3.7, 95% CI -5.5 to -1.9)
● ↓ disability from > 2 weeks to ≤ 3 months (WMD -2.9, 95% CI -4.9 to
-0.9)
● ↔ disability at ≤ 2 weeks
● Similar safety profile
Appears more effective than placebo for knee or hip OA pain;
effect size may be small. Less effective than NSAIDs
● SR of 15 RCTs (APAP vs placebo or NSAID) 🡪 5,986 patients
● Median trial duration 6 weeks
● APAP vs placebo 🡪 pain improvement of ~ 4/100; NNTs 4-16
● APAP vs NSAIDs 🡪 NSAIDs more effective for pain improvement,
functional status. Adverse GI event more likely with NSAID (NNH 17)
May slightly improve pain and physical function in patients
with hip or knee OA
● SR of 10 RCTs (vs placebo) 🡪 3,541 patients
● ↓ pain at 3-12 weeks (WMD -3.23, 95% CI -1.02 to -5.43), may not be
clinically important
● ↓ disability at 3-12 weeks (WMD -2.92, 95% CI -0.95 to -4.89), may not be
clinically important
● Abnormal liver function at 24 weeks
● RR 3.79 (95% CI 1.94-7.39); NNH 8-59
● Clinical importance uncertain
NSAIDs
- Alternative options for initial management or
add-on therapy - Lowest effective dose, continued for as
short as possible - Adverse effects (oral)
● Gastrointestinal
● Addition of PPIs or misoprostol ↓ occurrence of these
● Cardiovascular
● All NSAIDs ↑ CV risk except naproxen, which appears closer to
neutral
● Renal
● CNS
Special populations (CI/caution)
● Severe CKD, cirrhosis, GI ulcer, HF, CVD, HTN, asthma,
pregnant
NSAIDs (oral) - Evidence
Associated with improvement in pain, function,
stiffness at 3 months in knee OA
● SR of 137 RCTs 🡪 33,243
● Naproxen, ibuprofen, diclofenac all better than APAP for
pain
● Naproxen, ibuprofen, diclofenac, celecoxib all better than
APAP for function
● Naproxen, ibuprofen, diclofenac, celecoxib all better than
APAP for stiffness
● Nonselective NSAIDs had more GI AEs/withdrawals than
placebo or APAP
● CV AEs reported in < 50% of trials
NSAIDs (oral) - Considerations
- Gastroprotection
● If no risk factors: non-selective NSAID
● If 1-2 GI risk factors: celecoxib; or
non-selective NSAID + PPI or misoprostol
● If > 2 risk factors (or recent history of complicated ulcer):
celecoxib + PPI or misoprostol - CV risk
● Low risk: non-selective NSAID or celecoxib
● High risk: naproxen
● Concomitant ASA cardioprotection required: naproxen
recall risk factors
Topical NSAIDs
- Another first-line option
- Systematic reviews have found them to be effective &
safe in both acute & chronic pain (e.g., OA) - Adverse Effects
● Current data suggest minimal GI or CV adverse effects
● Rash, burning, itching - Frequently used in practice
- ACR 2019 recommends considering topical before
oral NSAIDs
Topical NSAIDs have been shown to be beneficial in the setting of osteoarthritis. And actually they’re considered recommended in the ACR guidelines to be considered before oral NSAIDS because of, of course, the lower risk associated with them. So there is more data around short-term effectiveness. And they’re actually, if you notice on ACR guidelines, there was no recommendation for hip osteoarthritis. So the concern is that the drug may not be able to penetrate because the hip is a much deeper joint and there’s concern that the drug may not be able to penetrate in there as well. So it could still be tried.
Topical Analgesics
Methyl Salicylate, Trolamine Salicylate,
Capsaicin, Menthol (Rubefacient)
* Available OTC
* Counterirritants & analgesics
* Alternative to systemic agents
* May be used as adjunct therapy
* May improve pain and joint stiffness
* Salicylate toxicity with overuse
* Burning sensation with Capsaicin & Menthol
* ACR 2019: conditional recommendation for capsaicin
in knee OA; conditional recommendation against for
hand OA
capsaicin actually might be beneficial in the hand, but it’s conditionally recommended against in the hand because of the risk of accidentally touching your eye and you don’t wanna touch it with capitation. So that’s the main reason why they actually conditionally recommend against it.
Duloxetine
- SNRI
- Evidence
● Appears to reduce pain and may also improve
function/disability
● NNH 6-12
● No significant differences in risk of serious adverse
effects - Avoid with other serotonergic agents or if CrCl < 30
- ACR 2019: conditionally recommended (knee, hip, and/or
hand OA)
Tramadol
- Hybrid Mechanism: mu receptors, 5HT & NE reuptake inhibition
- Similar adverse effect profile as other weak opioids
● More gastric upset, seizures, increased risk of suicide
● ? lower abuse potential - Drug interactions with antidepressants
- Costly
- Evidence
● Syst. Rev. of 22 RCTs (n=6496), treatment for 3 months
● Pain improvement (WMD 4/100, 95% CI 3-5; may not be clinically important)
● Function improvement (difference may not be clinically important)
● ↑ risk serious adverse events (RR 1.78, 95% CI 1.11-2.84) NNH 28-478 - ACR 2019: conditionally recommended
hat there may be improvement in pain and some of these patients, but the difference may not be clinically important in the studies. And there is, of course, risk of adverse effects with it.
Opioids
- “Not ideal agents for maintenance, but may be necessary”
● Patients who can’t take NSAIDs, all other options have failed,
non-candidates for surgery - Acetaminophen & Codeine (Tylenol #3 or #4)
● “Weak Opioid” - Strong Opioids
● E.g., morphine, hydromorphone, oxycodone
● Long-acting products usually offer better pain control - Potential for dependence & abuse with chronic use
● Patient selection & risk stratification (Opioid Risk Tool)
● Informed consent & opioid treatment agreements
● Indications for discontinuation of therapy - ACR 2019: conditionally recommended against, with
recognition that they may be used under certain circumstances
Glucosamine & Chondroitin
- Endogenous cartilage-maintaining substances
- Proposed mechanisms of action:
● Stimulate production of cartilage
● Prevent inflammatory cartilage destruction
● Maintain joint fluid viscosity - Onset of pain relief 1-3 wks
- Adverse effects
● Nausea, dyspepsia, diarrhea, allergies with shellfish sources - ACR 2019:
● Glucosamine strongly recommended against (knee, hip, and/or hand
OA)
● Chondroitin strongly recommended against for knee and/or hip OA,
but conditionally recommended for hand OA
Evidence Summary
* “Multiple meta analyses indicate glucosamine does not reliably improve
pain or function in OA. Any suggestion of benefit is at high risk of bias
associated with low quality studies, industry funding, and selective
reporting/publication.”
, there’s different salts, glucosamine hydrochloride and glucosamine sulfate. So it’s the sulfate that has more evidence of benefit than the hydrochloride. So if they’re going to use when I would steer them towards tha
Natural Health Products
- SAMe (S-adenosyl-L-methionine)
● Unclear efficacy
● May not improve pain in knee/hip OA
● May improve functional limitation vs. placebo
● May cause diarrhea, but relatively safe
● May increase serotonin levels - Avocado/Soybean Unsaponifiables (i.e. ASU)
● Appear to reduce pain and NSAID use in patients with knee/hip OA
● Systematic review of 4 PC, DB RCTs - MSM (Methylsulfonylmethane)
● May slightly improve pain & physical function - Vitamin D
● “Supplementation for 2 years did not reduce knee pain or cartilage
volume loss in patients with symptomatic knee OA”
Other Natural Health Products
- Antioxidants
● Do not appear effective for OA
● Systematic review of 9 RCT (Vit A, C, E, selenium, or combination) - Boswellia serrata extract
● Associated with improvement in knee pain, flexion and walking distance
over 8 weeks. - Ginger
● Not clearly superior to placebo
A useful resource for these products:
● www.albertarheumatology.com/natural-health-products/
Intra-Articular Therapy
Corticosteroid
- Triamcinolone 10-20 mg or methylprednisolone 20-40 mg
- Indicated with acute pain & inflammation
- 3-4 times per year maximum (and no more frequently than q3month)
- Repeated injections may damage cartilage
- Adverse effects: Risk of infection, post injection flare
- Pain relief
● Starts at 24-72 hrs
● Peaks: 7-10 days
● Can last 4-8 weeks
● Should minimize activity and stress on joint
for several days after injection - ACR 2019: strongly recommends (knee/hip);
conditionally (hand)
So you can’t really do this any more than three to four times a year and no more frequently than every three months. The challenges with that, that tends to wear off after four to eight weeks. So it tends to be when patients get this injection. It works for a little bit, but it tends to not quite make it to three months before you can have another injection. After they’ve had the injection, they should, patients should be educated to minimize activity and stress on the joint for several days after the injection.
