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