taking the pain out of osteoarthritis pain management
TRANSCRIPT
Dr. Mike Allan and Betsy Thomas
Taking the Pain Out of Osteoarthritis Pain Management
Methods
• Umbrella review of systematic reviews of RCTs
• Start with 1757 studies
• 235 studies included
• meta-analysis was infrequently reported so we ended up analyzing RCTs.
Can Fam Physician 2020;66(3)
Interventions
• Acetaminophen
• Oral NSAIDs
• Topical NSAIDs
• Serotonin and norepinephrine reuptake inhibitors (SNRI)
• Tricyclic antidepressants (TCAs)
• Cannabinoids
• Exercise
• Counselling
• Platelet-rich plasma (PRP)
• Viscosupplementation
• Glucosamine
• Chondroitin
• Intra-articular corticosteroids
• Rubefacients
• Opioids
Pain Outcomes: Change in Scale
• On a 0-10 point scale: Baseline ~6/10. - Placebo reduces Pain: ~1.4- Treatment: ~2.0
Placebo
Treatment
BMJ. 2013 May 3;346:f2690
How do these numbers work?
2.5 7.55 10
7.54.5 6
40%
60%
Placebo
Treatment
Clinically Meaningful Change
Who gets 30% better
4
Move 1.4
Move 2.0
0
Responder Outcomes
• Focus was RCTs that included responder outcomes for pain
• Pain prioritized over function because:• Function is rarely reported while pain is almost always reported
• Pain often the presenting issue in primary care offices
• Chose dichotomous outcomes versus Standard Mean Difference
• Created a hierarchy of responder outcomes which included (but not limited to):• OMERACT-OARSI response
• % improvement on a pain scale that is closest to 30% improvement
• Change of at least 1 on a 10- or 11- point VAS
BMJ open. 2019 Sep 24;9(9):e030060..
Meta-Analysis
• Completed for each intervention overall• i.e. Proportion of patients who achieved meaningful pain improvement
compared to placebo/control
• Subgroup analysis completed (where possible):• Size of trial (<150 patients vs > 150 patients)
• Funding (industry or clearly publicly funded)
• Duration (≤4 weeks, >4 to <12 weeks and ≥12 weeks)
RCTs we found and Limitations
Intervention RCTs Found
RCTs withResponder
Of Those with a Responder Analysis: Meet all Criteria>150 Patients >8 weeks Publicly Funded
Exercise 237 11 (5%) 5 10 11 5 (2%)
Steroid Injections 32 7 (22%) 1 7 3 0
Duloxetine 6 6 (100%) 6 6 0 0
Oral NSAIDs 115 43 (37%) 42 23 1 1 (1%)
Glucosamine 31 9 (29%) 4 7 3 3 (10%)
Topical NSAID 30 22 (73%) 15 8 0 0
Chondroitin 19 9 (47%) 4 9 1 1 (5%)
Viscosupplementation 166 31 (19%) 17 26 1 1 (1%)
Opioids (Oral) 32 15 (47%) 12 9 0 0
Acetaminophen 10 2 (20%) 2 1 0 0
Total 649 155 (24%) 108 106 20 11 (2%)
And now the results….
• In order of efficacy…..drum roll please….
Exercise
• 11 RCTs (1367 pts) followed 6-104 wks
• Results• Attained meaningful pain relief: 47% vs 21%, NNT=4• Most common type of exercise was physiotherapy-guided exercise programs
• Note: Benefit seen regardless of size or length of trial
Clinical Pearls:
Does not matter what type of exercise –just get moving!
Intra-articular Corticosteroids
• 7 RCTs (706 patients), 4 to 24 weeks
• Results:• Attained meaningful pain relief: 50% vs 31%, NNT=6
• Concerns:• Studies ≥12 weeks: no difference from placebo
• Industry funded trial was NSS
Clinical Pearls:
• Choice of steroid does not matter (eg.methylprednisolone, triamcinolone)
• Risk of joint infection rare – 1 in >14,0001
• Unclear if erodes cartilage
1. Tools for Practice #135 March 2015
SNRIs (Duloxetine)
• 6 RCTs (2060 patients), 10 to 18 weeks
• Results:• Attained meaningful pain relief: 64% vs 43%, NNT=5
• Most common dose was 60-120mg qd
• Concerns:• All industry funded trials
Clinical Pearls:
• Doses studied were mostly 60-120mg qd1
• Adverse events1: overall (NNH 6), withdrawal (NNH 17), GI (NNH 4)
• Cost: ~$110 for 90d supply (60mg) –covered on most plans
1. TFP Duloxetine and OA. In Press.
Oral NSAIDs• 43 RCTs (27,657 patients), 4 to 104 weeks
• Results• Attained meaningful pain relief 57% vs 39%, NNT=6
• Note: Both COX-2 inhibitors and traditional NSAIDs effective
• Concerns• One publicly funded trial showed smaller benefit
Clinical Pearls:
• COX-2 inhibitors and traditional NSAIDs, except naproxen, may increase the risk of major vascular events and death. 1
• naproxen or low- dose ibuprofen possibly preferred for patients at risk of CV disease1.
Tools for Practice #101 Jan 2018.
Glucosamine
• 9 RCTs (1643 patients), 4 to 156 weeks
• Results: • Attained meaningful pain relief: 47% vs 37%, NNT=11
• Concerns• Publicly funded trials found
no benefit vs placebo
Glucosamine (Allocation Concealment)
Osteoarthritis Cartilage. 2010; 18(4):476-99. Cochrane 2005; (2):CD002946.
Topical NSAIDs• 22 RCTs (7265 patients), 1 to 12 weeks
• Results• Attained meaningful pain relief: 61% vs 47%, NNT=8
• Concerns:• All industry funded trials
• Effect size smaller with larger (≥150 patients) and longer (≥12 weeks) trials, but still statistically significant
Clinical Pearls:
• Lack evidence to recommend one formulation over another (gels/creams)1
• Withdrawals for adverse effects similar toplacebo1
Tools for Practice #40 February 2015
Viscosupplementation(hyaluronic acid)
• 31 RCTs (6254 patients), 2 to 160 weeks
• Results: • Attained meaningful pain relief: 53% vs 44%, NNT=11
• Concerns:• One publicly funded RCT: no benefit
• Effect size lower in larger (≥150 patients) trials, but still statistically significant
Neurology® 2015;84:794–802. JAMA. 2008 Mar 5;299(9):1016-7.
Viscosupplementation(hyaluronic acid)
Other Research
Viscosupplementation(hyaluronic acid)
• So why do we see some difference in Practice?????
Bannuru RR, Schmid CH, Kent DM, et al. Ann Intern Med. 2015; 162:46-54.Neurology® 2015;84:794–802. JAMA. 2008 Mar 5;299(9):1016-7.
Expensive MattersParkinsons: Motor Symptom score change, All Stat diff,Levodopa 14, expensive placebo 8, cheap placebo 4Pain: High cost = better mean pain↓ ~12mm
85% high cost got better vs 61% discounted
Placebo Matters but Injections Matter More!Remember that Placebo effect is 1.4 out of 10 and ~40% will report meaningful improvementIntra-articular placebo vs oral placebo: Effect size 0.29 (0.04-0.54). Some better still.
Chondroitin
• 9 RCTs (2477 patients), 12 to 48 weeks
• Results:• Attained meaningful pain relief: 57% vs 45%, NNT=9
• Concerns• Publicly funded trials did not show a benefit vs placebo
Chondroitin
High Quality
Low Quality
Others also found that the certainty of benefit for Chondroitin was Low
Opioids
• 15 RCTs (6266 pts), 1.5 - 24 weeks
• Results• Attained meaningful pain relief: 47% vs 43%, NNT=32
• Concerns:• All industry funded trials
Do
Opioids
• Good to 4 weeks but not beyond
• Opioids do not work more than placebo for “Chronic Pain” in Osteoarthritis
Acetaminophen
• 2 RCTs (991 patients), 6-24 weeks
• Results: • No difference between acetaminophen and placebo
• Concerns• All industry funded trials
Clinical Pearls:
• No difference in overall AE or serious AE• Increases the risk of elevated liver
enzymes (>1.5x normal)1, NNH=21, 7% vs 2%
1. Tools for Practice #171 September 2016
Other Interventions
• Rubefacients: 1 RCT found (113 patients) • Capsaicin 0.025% no difference from placebo at 4, 8 or 12 weeks
• No responder analysis found for:
Tricyclic Antidepressants
Platelet-rich Plasma Injections
Cannabinoids Counselling
Summarizing the InterventionsTreatment Type RCTs Intervention Control NNT Time Frame
(Weeks)Evidence Certainty
Rate Ratio
Exercise 11 47% 21% 4 6 - 104 Low 2.4 (1.8-3.1)
Steroid Injections 8 50% 31% 6 4 - 24 Very Low 1.7 (1.2-2.6)
Duloxetine 6 64% 43% 5 10 - 18 Moderate 1.5 (1.3-1.9)
Oral NSAIDs 43 57% 39% 6 4 - 104 Moderate 1.44 (1.36-1.5)
Topical NSAIDs 22 61% 47% 8 1 - 12 Low 1.3 (1.2-1.4)
Glucosamine 9 47% 37% 11 4 to 156 Very Low 1.3 (1.0-1.7)
Chondroitin 9 57% 45% 9 12 - 48 Moderate 1.3 (1.1-1.4)
Viscosupplementation 31 53% 44% 11 2 - 160 Very Low 1.2 (1.1-1.3)
Opioids (Oral) 15 47% 43% 32 1.5 - 24 Very Low 1.2 (1.0-1.3)
Acetaminophen 2 47% 43% NSS 6 - 24 Low 1.2 (0.8-1.6)
Do Patients & Clinicians See the Same Things?
Are we speaking the same language?
Description EU Assigned
Meaning
Very Common >10%
Common 1-10%
Uncommon 0.1-1%
Rare 0.01 – 0.1%
Very Rare <0.01%
Lancet 2002; 359: 853–54
Are we speaking the same language?
Description EU Assigned
Meaning
Patients Perceived Chance
Very Common >10% 65%
Common 1-10% 45%
Uncommon 0.1-1% 18%
Rare 0.01 – 0.1% 8%
Very Rare <0.01% 2%
Lancet 2002; 359: 853–54
Shared Informed Decisions: Do Patients Want It?
• Results vary but 27-55% of population wants1
• Factors1
• presenting problem (more for procedures)
• age (more if younger)
• gender (more if female)
• social class/education (more if more)
• “some patients clearly gain reassurance from the medical profession adopting the politically incorrect paternalistic approach.”• Example: ~62% preferred doctors' opinion over any presentation (pictures or
numbers) for CVD interventions1b
1) BMJ 2000;321:867-71, Med Care 2000;38:335-41, Ann Fam Med 2011;9:121-127. Patient Education and Counseling 2011doi:10.1016/j.pec.2011.02.004 2) BMJ 2000;320:58
What do Decision-Aids Accomplish?Time: 8 minutes less to 23 minutes longer (median 2.5 minutes longer)
Usual care Decision Aid Studies (patients)
Knowledge score: from 0 (none) - 100 (perfect)
57% 70% 42 studies (10,842 patients)
Proportion who Understand Risk
30% 54% 19 studies (5868 patients)
Congruence between choice and values
32% 50% 13 studies (4670 patients)
Decisional conflict (<25 decisions made; >38 delayed decision)
13-49 7 lower 22 studies (4343 patients)
Decision made by Practitioner
17% 10% 14 studies (3234 patients)
Cochrane Database Syst Rev. 2014 Jan 28;1:CD001431.
Either of these methods are pretty good
RRR had worse understanding of risk vs ARR BUT more perceived risk with RRR
NNT not helpful: Hard to understand
Systematic Rev: 91 studiesAnn Intern Med. 2014;161:270-280.
Review of methods for promoting shared informed decision-making
• 91 studies
• Visual aids (icon arrays and bar graphs) improved understanding and satisfaction.
• Absolute risk > RRR for maximizing accuracy • But RRR more likely to get people to accept therapy.
• NNT reduces understanding.
Ann Intern Med. 2014;161:270-280.
PEER Decision Aid for Osteoarthritis
Can Fam Physician 2020;66(3):191-3.