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Pharmacotherapy ofOsteoarthritis
Goals of Drug Treatment
• Rapid relief of pain
• Slow relief of symptoms
• Slowing down the progression
Drugs Used For OA
ParacetamolNSAIDs
TramadolSteroid injectionsTopical Capsaicin
ViscosupplementationNeutraceuticals
Pain Relief
Paracetamol in OA
• Dose 2-4,000 mg daily
• May be used in doses up to 2,600 mg/d
continuously for 2 yrs with good safety
• More effective than placebo, less than NSAIDs
• Effect size 0.21 is small but significant
NSAIDs
NICE Guidelines
RFs for NSAID-induced Ulcers• Age >60 yrs
• Past history of peptic ulcer
• PH of adverse events with NSAIDs
• Concomitant steroid use
• High dose or multiple NSAIDs
• Individual NSAIDs– High: piroxicam, ketoprofen
– Low: Ibuprofen
Strand V et al. J Rheum 2011
NSAIDs: Take Home• NSAIDs are superior to placebo & paracetamol
• Pooled effect size 0.32
• Has substantial AEs
• Continuous use (particularly celecoxib) offers better pain relief, function & QoL, with fewer side effects
• Most NSAIDs increase vascular events:
– Diclofenac, indomethacin, meloxicam
– Ibuprofen reduces efficacy of aspirin
– Naproxen neither increases nor decreases
Tramadol
Intra-arti cular Steroid
IA Steroid
IA Steroid: Take Home
• Effect size 0.6, but short-lived
• More effective in patients with effusion
• 3 monthly use over 2 yrs found to be safe
and effective in Raynauld’s study
Viscosupplementation
Viscosupplementation
Viscosupplementation: Take Home
• Effect size small
• Administration cumbersome
• Local AEs common
• Should not be routinely used
?Disease Modification
Slow Relief of Symptoms
Tested MoleculesNeutraceuticals
DiacerinDoxycyclineCelecoxib
BisphosphonatesStatins
ColchicineHydroxychloroquine
Neutraceuticals
• Glucosamine sulphate• Chondroitin sulphate• Glycosaminoglycan
polysulphate (arteparon)• Curcumin• Resveratol• Anti-inflammatory factor
(AIF)• Phytalgic• Fish oil
• Boigito• Pomegranate• Green tea• Ginger• Indian olibaum• Turmeric• Cat’s claw• Devil’s claw• Ananas –
GlucosamineEponym/Authors
Year HCl/S No. FU period
Result summary S/NS
GAIT 2010 GHCL 77 24 mo JSN: GH-0.013, Pl-0.166 NS
Reginster 2001 GS 106 3 yrs GS-0.06 mm, Pl-0.31 S
Pavelka 2002 GS 101 3 yrs GS-0.04 mm, Pl-0.19 mm S
Poolsap review
2005 GS+ GHL
>1 yr Pooled RR 0.46; 95% CI 0.28 to 0.73
S
Wandel’s meta
2010 GS+ GHL
395 variable -0.2 mm (-0.3 to 0) NS
STOPP, 2009
Wildi et al, ARD, 2011
Chondroitin SulfateEponym/ Authors
Year No. FU period
Result summary S/NS
Wildi, et al 2011 31 12 mo MRI CVL: CS: 3.71, Pl: 6.12 P=0.021
STOPP 2009 309 2 yr JSN: CS: 0.07, Pl: 0.31 P<0.0001
Zurich 205 150 2 yr JSN: CS: 0, Pl: 0.14 P=0.04
Hochberg meta
2010 2 y Reduction of SJN: 0.13 mm P=0.0002
Diacerin
Pham et al. Osteoarthtrhritis & cartilage, 2004
Louthereno et al, Osteoarthritis & cartilage, 2007
Fagnani et al, Pharmaconomics, 1998
DiacerinEponym/ Authors
Studied joint
Year No. FU period
Result summary S/NS
Dougados Hip 2001 204 3 yr JSN: D 0.18mm, P 0.23 P=0.04
Pham et al Knee 2004 85 1 yr % JSN>0.5mmD: 18.9, IAH: 17.7, P: 20.3
P=0.90
Fidelix meta
HipKnee
2009 1228 Variable Hip=0.04Knee=0.85
Conclusions
• Body of evidences not enough
• Follow up period short
• Sample sizes small
• Structure modifying effects variable
– Where positive, effect size small
Guidelines
NICE
OARSI
EULAR
ACR
NICE Guidelines
ACR 2012 Non-Pharmacological: Strong
• Cardiovascular (aerobic) and/or resistance and
land-based exercise
• Aquatic exercise
• Lose weight (for persons who are overweight)
ACR 2012 Non-Pharmacological: Conditional
• Medial taping of patella
• Medial wedging insole in lateral compartment OA
• Lateral wedging insole medial compartment OA
• Thermal agents
• Walking aids
• Tai chi programs
ACR 2012: Pharmacological…
Acetaminophen
Oral NSAIDs
Topical NSAIDs
Tramadol
IA steroids
ACR 2012: Pharmacological…
• Should not use:
–Chondroitin sulfate
–Glucosamine
– Topical capsaicin
• No recommendation:
– IA hyaluronans
–Duloxetine
–Opioids
Conclusions
• Structure modifying therapy with proven and unequivocal benefit:– “Although we are not there yet, we are getting
much closer to realizing the dream….”– RF Loeser:
– Osteoarthritis: A disease of the joint as an organ. Arthritis & Rheumatism 2012: 64: 1697--1707