PREVIEW ONLY 30/05/2013. Andrew Ellis. Dr Donald Kuah. Conservative Options in Management of Knee Osteoarthritis

Transcription

1 Need technical support for this live event? Please call , then press 1 Be sure to convert to your own time zone at NOTE: You will be initially asked for the address associated with this webinar account Say I m a webinar attendee I don t have an account Andrew Ellis BSc (Ex. Sci), M. Phty Conservative Options in Management of Knee Osteoarthritis World Health Webinars CEO World Health Webinars (Australia/NZ) Host Presented by: Dr DONALD KUAH - Sport and Exercise Physician Will commence LIVE from Sydney, Australia at 7:30pm AEDT Be sure to convert to your own time zone at Click red button to minimise Dr Donald Kuah Dodgy computer speakers? Select Telephone and call in toll - FREE to hear the presentation Founding practitioner at Sydney Sports Medicine Centre in Olympic Park and Sydney Sportsmed Specialists in CBD. NSW Institute of Sport Medical Director from 2000 to 2012 Medical Consultant to NSWIS You will be muted during every webinar. Make as much noise as you like :) Questions? We ll answer them all at the end Sport and Exercise Physician Chief Medical Officer to the Wests Tigers NRL team, Consultant Sports Physician to AFL team GWS and has previous team doctor for Sydney Kings. Involved in Olympic Games in Sydney 2000, Athens 2004, Beijing 2008 and London 2013 For his services to sports medicine, the Commonwealth awarded the year 2000 Sports Need technical support? Please call , then press 1 You will need to tell them that you are a webinar attendee and do not have an account with Citrix. Chapter author for two internationally published sports medicine textbooks as well as various research and educational articles on sports medicine. 1

2 Conservative Options in Management of Knee Osteoarthritis ADVERTISING -media, internet The stats advances TKRs % in private hospitals. Increase 7.2% from 2009 Only 75% are satisfied Unicompartmental 37.3% less unicompartmental knees in 2010 compared to yr revision rate 13% compared to 5% of TKRs 2

3 UNISPACER - What were they thinking? HEMICAP WHAT ARE WE TRYING TO AVOID? HUMAN ERROR COMPLICATIONS Optimal management of knee OA requires a combination of non-pharmacological and pharmacological treatment modalities EULAR Recommendations 2003: An evidence based approach to the management Full notes of available knee osteoarthritis. after purchase Jordan et al;ann from Rheum Dis 2003;62:

4 Non-pharmacological Treatment Severe OA Education/lifestyle modification Weight loss (if applicable) Exercise Non-specific Specific muscle training Surgery Partial/Total joint replacement or Surgery (joint preserving) Osteotomy, resurfacing Athroscopic investigation and washout -Advanced non-surgical interventions Injections of HA / steroids few some Dietary factors Simple non-surgical interventions, Injections of HA, NSAIDs, other drugs, physio/occupational therapy, orthoses, other aids all Knee sleeve, walking aids etc Self help Simple analgesics, topical agents, lifestyle, nutraceuticals Mild OA Information and Advice Education, weight loss, exercise, lifestyle alterations Numbers of people Dieppe & Lohmander, Lancet Point summary recommendations EULAR recommendations 2013 Initial assessment to be a biopsychosocial approach, including physical status, ADLs, participation (work, education, leisure, social, family), mood, health education and beliefs Rx should be individualised Mx plans should be individualised Lifestyle changes should be individualised Exercise education- link to person s preferences, lifestyle and build small doses slowly Daily exercise regimen- strength and aerobic. Aim to achieve in own environment Education re weight loss Appropriate footwear. Lateral wedge rejected Walking aids and ergonomic aids Vocational modifications Effects of strength on the incidence and progression of knee OA- Mikesky et al (Arthritis Care and Research Oct 2006) 221 adults with OA knees (mean age 69) RCT Strength Ex vs ROM ex over 30 months Rate of loss of strength less in strengthening group Rate of joint space narrowing reduced by 26% in Strengthening group Medscape Orthopaedics Knee OA: Conservative biomechanical strategies Neil Reeves et al- Feb 2011 Footwear interventions Gait modification Valgus Knee braces Muscle strengthening 4

5 After patients are diagnosed with knee OA, what do they do? Kelly Grindrod et al, Arthritis Slides are Care limited. and Research April 2010 After 6 months of receiving a diagnosis of knee OA, participants made several lifestyle changes without the advice of a health professional and saw improvements in pain and function Obesity and Increased Burden of Hip and Knee Joint Disease in Australia Ackerman & Osborne, BMC Musculoskeletal Disorders Australians >39yo with BMI comparison Concluded Obesity- 7 times increased knee OA Pharmacological Rx Aims: Ideal Treat symptoms Disease modification (or reversal?!!) Allow continued exercise / sport/ work Low side effect / allergy profile Minimal cost Non-invasive OA - National Clinical Guideline for Care and Management in Adults UK survey 2004: Analgesia Use By the National Collaborating Centre for Chronic Conditions and published by Royal College of Physicians % paracetamol 50% NSAIDs If you fall asleep go to (Pgs ) 64% non-selective NSAIDs 36% selective COX-2 inhibitors 5

6 Simple Analgesia: Evidence Surprisingly few studies (with small numbers) directly assessing efficacy 6/52 RCT: Paracetamol superior to placebo 4/52 RCT: Comparably efficacious to low-dose naproxen and ibuprofen Long term use less convincing Paracetamol / Acetominophen Knee OA: painful condition (mild-mod)- good evidence, less in other joints- Towheed et al 2006, Cochrane review and metaanalysis (MA) Paracetamol is effective in mild-moderate pain states Consider regular dosing Slow release? Simple Analgesia: Paracetamol Recommended 1 st line treatment Opioids Avouac et al (2007) MA of 18 RCTs Daily total of 4g divided doses well-tolerated Better GIT tolerability than NSAIDs Moderate to strong These effect notes on pain are a preview. Mild to moderate effect on function Problem is tolerability. Stronger the effect, greater the side effect profile. 25% dropout of studies-higher with stronger opioids (compared to 7% placebo) Side Effects of Opioids Topical NSAIDs Nausea (30%) No Long term effect over placebo Constipation (23%) Dizziness (20%) Somnolence (18%) Vomiting (13%) Efficacy of topical non-steroidal anti-inflammatory drugs in the treatment of osteoarthritis: meta-analysis of randomised controlled trials Jinying Lin, visiting scholar, 1 Weiya Zhang, senior lecturer in epidemiology, 1 Adrian Jones, consultant, 2 and Michael Doherty,professor 1 BMJ August 7; 329(7461): 324. Several RCTs show short term benefit (less than 4 weeks)- NSAIDs found in synovial fluid, but maximum of 15% plasma concentration compared to standard oral use. OARSI recommendation for use 6

7 Oral NSAIDs: Rationale for Use Analgesic properties (OA is painful) Anti-inflammatory properties (OA, especially late, often has inflammatory features) Bjordal et al,bmj- Nov 2004 Meta-analysis "NSAIDs can reduce short-term pain in osteoarthritis of the knee slightly better than placebo, but the current analysis does not support long-term These notes use of are NSAIDs a preview. for this condition, "As serious adverse effects are associated with oral NSAIDs, only limited Full use notes can be available recommended. after purchase from Supported by UK National Clinical Guidelines 2008 NSAIDs: The Evidence NSAIDs Most studies indicate NSAIDs slightly better than placebo for short-term pain Evidence does not support the long-term individual use of NSAIDS Traditional- diclofenac, ibuprofen, naproxen Selective COX2 inhibitors- meloxicam (Mobic), celecoxib (Celebrex)?Combined use with PPIs in those at risk of GI effects? Bjordal et al; BMJ 2004 NSAIDs: Side Effects Gastrointestinal: Cardiac: Peptic ulcer Blood pressure increased Reflux oesophagitis Congestive cardiac failure Full notes available after (onset purchase and acceleration) from Bleeding/Perforation Adverse cardiac events NSAIDs: Side Effects Renal dysfunction & failure Liver dysfunction Drug interactions: Antihypertensive drugs Risk: Age Concurrent Medications Duration Treatment Pharmacokinetic interactions with renally-eliminated medications (e.g. lithium) 7

8 Effective dosage equivalents: NSAIDs Celecoxib 200 mg Diclofenac 100 mg Ibuprofen 2400 mg Meloxicam 7.5 mg Naproxen 1000 mg NSAIDs: Practice Points NSAIDs can be justified in the Side effect profile short-term management of pain & inflammation Aspirin & indomethacin most toxic Simple analgesics first Full notes available after purchase Effective dose from equivalents Consider patients unresponsive to paracetamol or as top up reliever Can consider gut protection (no proof of efficacy) May be of more use in more severe OA AD HOC usage Topical Capsaicin Reversibly desensitises nociceptive C fibres Only trial using capsaicin: superior to placebo Segal et al (2004) Well-tolerated GLUCOSAMINE Possibly consider with 1 st line treatments? Corticosteroid Injection: Rationale Corticosteroid Injection: Evidence Analgesic properties (OA is painful) Limited studies, despite long-standing use Anti-inflammatory properties (OA, especially late, often is inflammatory) Some studies show no benefit over placebo Recommended for flare, but evidence suggests benefits are short-lived- 1-4wks 8

9 Corticosteroid Injection: Local Side Effects Skin Ligament / tendon rupture Fat atrophy Pigmentation These changes notes are a Avascular preview. necrosis (temporary) Steroid arthropathy? Flare Full hours notes available after purchase from Disease progression? Joint or soft tissue infection Corticosteroid Injection: Systemic Side Effects Facial flushing (can last for 1-2 days) Allergy (<1%) Hyperglycaemia in diabetics * Approximately 2% enters systemic circulation Viscosupplementation Intra-articular injection Hyaluronan and hylan derivatives Hyaluronic Acid (HA) HA Gel-like aminoglycan Responsible These for the elasticity notes are and a viscosity preview. of synovial fluid Role in Joint Lubricate Cushion Protect articular surfaces (cartilage) Hyaluronic Acid in OA Hyaluronan is present in cartilage and synovial fluid Decreased molecular weight of HA Decreased concentration of HA Entirely responsible for the elasticity and viscosity of Synovial Fluid As result synovial fluid in OA has reduced elasticity and viscosity Lubricates, cushions, and protects (absorbs shock) the articular surfaces in a healthy knee. 9

10 Synovial Fluid Elastoviscosity Dynamic Moduli at 2.5 Hz (walking on a flat surface) Elasticity (Pa) Viscosity (Pa) Normal: yr old (n=16) 117 ± ± 8 Osteoarthritis (n=11) 8 ± 5 5 ± 3 Hyaluronan in synovial joints Continuously renewing intercellular matrix Both viscosity and elasticity important to function Shock absorption Full notes and available protective lubrication after purchase from SYNVISC (Hylan G-F 20) E.A. Balazs (1982) in Disorders of the Knee, J.B. Lippincott Hyaluronan What are some potential modes of action? Hyaluronic Acid, HA, Sodium Hyaluronate 12,000 repeating units Chemically Identical in all species Turnover 8-10g every day Exogenous HA - Not Just a Lubricant Easy for patients to understand, but... HA has short residence time in synovial fluid irrespective of molecular weight Synovial fluid Synovial tissues Cartilage and synovial surfaces 0 Day 1 Day 3 Day 7 Day 28 Days after a single injection 10

11 Mean improvement from baseline 1. lubricates and cushions joints These 2. Protects notes are cartilage a preview. 3. Synvisc is cross linked to increase residence time Full notes 4. Restores available joint homeostasis after purchase from 5. Dampens nociceptors Hyaluronan and Chondrocytes Incorporated into chondrocytes Direct action via CD44 receptors Increases production of EC matrix (DNA, glycosaminoglycan, hydroxyproline) May lead to production endogenous hyaluronan Radiologic Grades Medial x-ray % better or grade These notes are much a preview. better I 91% II 80% III 76% IV 58% Reference: Lussier A, Cividino AA, McFarlane CA, et al. Viscosupplementation with hylan for the treatment of osteoarthritis: findings from clinical practice in Canada. J Rheumatol. 1996;23(9): SYNVISC (hylan G-F 20) vs Triamcinolone Hexacetonide (TH) Prospective, multicenter, randomized, single-blind, parallel-group, 26-week trial 1 WOMAC is a trademark of Nicholas Bellamy, MD. Mean improvement change in WOMAC A1 (pain when walking on a flat surface: 0-4 scale) 1 P = Injection Week 3 Injections P = SYNVISC (n = 113) TH (n = 102) 1. Caborn D et al. J Rheumatol. 2004;31: Please see full Prescribing Information. Cochrane Overview Viscosupplementation Does it work? Key Results of the Cochrane Review of HA for Knee OA Treatment The HA class was superior to placebo for the treatment of knee OA Synvisc was significantly better than placebo for the treatment of knee OA Synvisc improved pain and function better than intra-articular corticosteroids and similar to continuous NSAIDs at 5-13 and weeks after treatment The majority of Synvisc studies in the class analysis had more robust effect sizes than studies with other HA products 11

12 Cochrane Overview Synvisc vs. Other OA Therapies Significantly better These than corticosteroids notes are a at preview and weeks following therapy Comparable to continuous NSAIDs Summary Studies provide strong support for the incorporation of SYNVISC into routine clinical care paradigms Journal of Rheumatology 2004 Hyaluronic Acid vs IA Steroid Caborn Study supporting Synvisc efficacy for at least 6 months & vs IA steroids All grades OA included BMI > 30 Primary endpoint examines pain assessment Peak effect time established Also important in displaying efficacy rates between IA steroids and Synvisc Secondary endpoints in functionability Flare: Pain and Swelling CONTRAINDICATIONS Transient local reactions ~ 5-8% (pain and/or swelling) Local reaction does not predict treatment failure: ~ 70% are clinically improved (most will go on to receive further injections) Venous or lymph stasis Infected joint Hypersensitivity Caution for allergy to feathers, avian products, eggs National Clinical Guidelines Review of Bellamy MA (40RCTs) and 4 other RCTs the evidence seems to suggest a benefit of reducing pain up to 3 months after a series of 3-5 injections, although the effect size is generally small No long term effect / disease modification Practical Points NHS deems would have to be 3-5 times more effective for consideration of use- effect is small Better with mild to medium Slides OA are limited. Use for particular aims? Use to enable exercise, strengthening and wt loss? 12

13 Dietary and Nutritional Factors Other Treatments Anti-oxidants? Vitamins? Chondroitin sulphate? Other Anti-oxidants / Vitamin C Studies: OA chondrocytes have lower antioxidative capacity than normal regions in same knee OA chondrocytes cultured with ascorbic acid maintained size, glycosaminoglycan production oxidative stress contributes to catabolic changes? Vitamin C Studies in guinea pigs found a greater rate of spontaneous OA in Vit C supplemented animals! Applicability to humans Current guidelines: do not exceed RDA for Vit C Other treatments Foods rich in n-3 (omega-3) fatty acids (which contain α-linolenic acid, found in soybean, canola, fish oils) tend to result in less pro-inflammatory markers Animal studies Reduced inflammatory markers (IL-6,10,12; TNF, PGE-2, TBX-2, LTB4) Potentially beneficial on cartilage metabolism Arachidonic acid is an n-6 PUFA, and precursor to proinflammatory PGE2, the presence of which correlates with OA severity n-6 PUFA found in saffron, corn, soybean sunflower, meat Other treatments Clinical trials for omega-3 PUFA supplementation in rheumatoid These arthritis notes can are result a in: preview. improved strength tenderness Full NSAID notes use available after purchase from More research needed in all forms of arthritis 13

14 Avacado / Soybean Unsaponifiables (ASUs) Green Tea Unsaponifiables = oily fraction that after hydrolysis do not produce soap 6 month RCT resulted in improved functional score (delayed onset 2/12); 300mg ASU No change in x-ray progression / structure modification 3 of 4 rigorous RCTs suggest effective symptom-modification In vitro display anabolic, anticatabolic, anti-inflammatory effects on chondrocytes Contains antioxidants (catechins) Studies suggest possible preventative role in OA in-vivo (mice) in-vitro (bovine) in-vitro human Via inhibition of IL-1 induced collagen degradation No Clinical evidence Asian Herbal Remedies Some extracts (such as SKI 360X, a mixture of extracts) have also inhibited IL-1 collagen degradation More studies needed for Slides these treatments are limited. Other Nutraceuticals Not shown or little evidence for: Vitamins B Boron Bromelain Rosa canina Willow bark Flavenoids Platelet Rich Plasma Therapy PRP Therapy Controversial but became more prominent after Tiger Woods use Anitua E, Sánchez M, Nurden AT, Zalduendo MM, De La Fuente M, Azofra J, et al. Platelet-released growth factors enhance the secretion of hyaluronic acid and induce growth factor production by synovial fibroblasts from arthritic patients. Rheumatology. 2007;46(12): Problem is the different products and protocols used Italian study- 150 subjects comparing, Hyalanurase and PRP- Kon E, Filardo G, Presti ML, Delcogliano M, Iacono F, Montaperto C, et al. Utilization of platelet-derived growth factors for the treatment of cartilage degenerative pathology. Bologna, Italy. Electronic poster presentation International Cartilage Repair Society Meeting, Warsaw Poland, October (then published in Arthroscopy Nov 2011) 14

15 Stem Cell Therapy Bone marrow, cord, fat, muscle derived Mainly anecdotal, case series or animal studies Driven by commercial world Costly both for treatment and research Fat Derived Stem Cell Therapy? HiQ cell Promising results These so far notes are a preview. Current Level 1 Double blind RCT- 12 months Recent World Health Webinar by Dr Diana Robinson UK study announced July study of 70 subjects 15

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