The management of osteoarthritis

For Primary Care Physician

Prevalence of Arthritis in US Adults*■ 49.9 million (22.2%) with self-reported, physician-diagnosed arthritis†1

■ 21.1 million (9.4%) with arthritis and arthritis-attributable activity limitation1

■ Affects more women than men in every age group2

0

20

40

60

80

100

18–24 25–34 35–44 45–54 55–64 65–74 75–84 85+

Women Men

Age Group, years

* Data sources: 2007-2009 data from the National Health Interview Survey (NHIS). † Includes multiple forms of arthritis.HCP=health care professional.1. CDC. MMWR Morb Mortal Wkly Rep. 2010;59(39):1261-1265.2. Graphic adapted from CDC. NHIS Arthritis Surveillance: Arthritis Prevalence in Women and Men.

www.cdc.gov/arthritis/data_statistics/national_nhis.htm. Accessed January 12, 2011.3. CDC. MMWR Morb Mortal Wkly Rep. 2009;58(16):421-426.4. Hootman JM, Helmick CG. Arthritis Rheum. 2006;54(1):226-229.

■ Arthritis and rheumatism leading causes of disability in US3

■ By 2030, a projected 67 million in US will have HCP-diagnosed arthritis4

US

Adu

lts (%

)W

ith A

rthr

itis

Osteoarthritis: burden of disease

■ One in five people in the UK have arthritis1

■ Arthritis is the largest single cause of physical disability in the UK2

■ Osteoarthritis (OA) is the most common form of arthritis3

■ OA is associated with considerable burden of disease – second only to cardiovascular disease in causing severe disability3

OA in Primary Care

■ Most patients with OA are managed in Primary Care4

■ Overall, muscloskeletal problems account for one in ten (20%) of General Practice consultations4

■ GPs have an opportunity to optimise patient care in OA

Factors Implicated in the Development of OA

Cartilage breakdown

Obesity

Anatomic abnormalities

Microfractures and bony

remodeling

Loss of joint stability

Trauma

Aging

Genetic and metabolic diseases

Inflammation

Immune system activity

Compromised cartilage

Biophysical changes• Collagen network fracture• Proteoglycan unraveling

Biochemical changes• Inhibitors reduced

• Proteolytic enzymes increased

Abnormal stresses Abnormal cartilage

Mandelbaum B et al. Orthopedics. 2005;28(2 suppl):s207-s214.Adapted with permission from 2002 Medtronic Sofamor Danek, Basic Bone Biology.

EULAR Diagnostic Criteria for Knee OA (2010)

■ Based on review of studies from 1950-2008 and expert consensus ■ Focuses on clinical diagnosis: presence of three symptoms and

three signs correctly diagnoses 99% of cases

SymptomsSymptoms1 Persistent knee pain √2 Limited morning stiffness √3 Reduced function √

SignsSigns4 Joint crepitus √5 Restricted movement √6 Bony enlargement √

EULAR=European League Against Rheumatism.Zhang W et al. Ann Rheum Dis. 2010;69(3):483-489.

ACR Diagnostic Criteria for Knee OA (1986)

■ Clarified and standardized definition of osteoarthritis Joint symptoms and signs associated with defective integrity of

articular cartilage and changes in underlying joints at bone margin ■ Focuses on clinical examination of knee pain plus:

■ Sensitivity, 95%; specificity, 69%

Presence of 3 of the followingPresence of 3 of the following1 Age >50 years √2 Morning stiffness <30 minutes √3 Joint crepitus on active motion √4 Bony tenderness √5 Bony enlargement √6 No palpable warmth of synovium √

ACR=American College of Rheumatology.Altman RD et al. Arthritis Rheum. 1986;29(8):1039-1049.

Key principles5: EULAR guidelines

1. Treatment should be tailored to the patient2. The relationship between the healthcare team

and the patient should be a two-way process3. Using tools can help to assess the patient’s pain

and disability 4. Patient education has a significant impact on

pain management5. Treatment should be a combination of

non-pharmacological and pharmacological measures

Management options5: EULAR guidelines

6. Non-pharmacological management strategies should be incorporated

7. Paracetamol and NSAIDs should be used as first-line pharmacotherapy

8. There is evidence to support the use of some symptomatic slow-acting drugs for OA (SYSADOA)

9. Corticosteroid intra-articular injections can be useful in acute exacerbations

10. Consider surgery in patients unresponsive to medical management

Key principle 1Patient-tailored treatment

■ OA is a long-term, chronic condition and has a considerable impact on quality of life5

■ Treatment should: be tailored to the patient5

consider the individual patient’s needs in terms of both functionality and of pain relief5

■ It is likely that each individual patient will have to try a number of management options before finding the combination which works best for them5

Key principle 2 Doctor/patient relationship5

■ The relationship between the healthcare team and the patient is key

■ The patient should be an active partner in disease management

■ Involve the patient in treatment decisions and listen to their concerns

■ The patient is an expert in their disease: they know their pain better than anyone else and will have developed strategies to deal with it

Key principle 3 Using tools

■ Tools can help to assess the patient’s pain and disability

■ Tools include: rating scales questionnaires6

pain diagrams■ Using tools before and after treatment is also

useful to determine whether treatment is working

Pain drawings

Mark the area on your body where you feel the described sensations Use the appropriate symbolMark the areas of radiationInclude all affected areas

Numbness = = = = Pins and needles ° ° ° ° ° ° Burning xxxxxxxxStabbing / / / / / / /

Rating scales

■ Visual analogue scale

No pain

Worst possible pain

• Pain intensity

0 No pain

1 Mild

2 Discomforting

3 Distressing

4 Horrible

5 Excruciating

Key principle 4 Patient education

■ Studies suggest that education is around 20% as effective as NSAIDs, and can have a synergistic effect with other treatments8

■ Patient information and self-management strategies can empower patients to take control of their arthritis

■ Effective education techniques include: individual education packs regular telephone calls group education patient coping skills spouse assisted coping skills training5

Key principle 5 Management options

■ Treatment should be a combination of non-pharmacological and pharmacological measures5

■ Indirect evidence suggests non-pharmacological treatments offer additional benefits over and above treatment with NSAIDs and analgesics5

Goals of OA Management:OARSI Recommendations

Reducejoint pain and

stiffness

Reduce physical disability

ImproveHRQoL

Educate patients

Limitprogression of joint damage

Knee and Hip OA: Goals of Treatment

HRQoL=health-related quality of life; OARSI=Osteoarthritis Research Society International.Zhang W et al. Osteoarthritis Cartilage. 2008;16(2):137-162.

Maintain and improve joint

mobility

Integrated Approach to Treating Patients With OANonpharmacologicNonpharmacologic PharmacologicPharmacologic■ Patient education■ Phone contact (promote self-care)■ Referral to physical therapist■ Aerobic, strengthening, and/or water-based exercise■ Weight reduction■ Walking aids, knee braces■ Proper footwear, insoles■ Thermal modalities■ TENS■ Acupuncture

■ APAP■ Oral NSAIDs■ Topical NSAIDs and capsaicin■ Corticosteroid injections■ Hyaluronate injections■ Glucosamine, chondroitin sulphate, and/or diacerein■ Weak opioids and narcotic analgesics for refractory pain*

SurgicalSurgical■ Total joint replacement■ Unicompartmental knee replacement■ Osteotomy and other joint preserving surgical procedures

■ Lavage/debridement in knee OA†

■ Joint fusion after failure of joint replacement

* Pain resistant to ordinary treatment. † Controversial.TENS=transcutaneous electrical nerve stimulation.Zhang W et al. Osteoarthritis Cartilage. 2008;16(2):137-162.

Management option 6Non-pharmacological management

■ Life-style modification has an important role in management5,9

■ For example5: weight loss exercise

– quadriceps strengthening– range of movement– general fitness– hydrotherapy

assistive devices (canes and frames) appropriate footwear, insoles

Management option 6 Non-pharmacological management

■ Little formal evidence to support complementary therapies, but some patients derive considerable benefit

■ Examples of complementary therapies include:AcupunctureAlexander techniqueAromatherapyChiropracticeHydrotherapy MassageOsteopathyReflexologyTai chi

Management option 6 Non-pharmacological management

■ Self-management strategies can improve patients’ ability to manage their pain and disability of OA5

■ Access to patient organisations and support groups which provide help and advice

Management option 7Analgesia and NSAIDs

■ Use paracetamol as first-line therapy5

■ It is likely that the majority of patients will have already tried over-the-counter paracetamol5

■ In those patients with a poor response to paracetamol, NSAIDs should be considered5

■ NICE guidance recommends that COX-2 selective inhibitors should be considered only in patients who may be at high risk of developing serious gastro-intestinal (GI) adverse events10

■ The European Medicines Agency advised doctors that Cox-2 selective inhibitors should only be prescribed to people with arthritis at ‘the lowest effective dose for the shortest possible duration’. (EMEA 27 June 2005)

Management option 7 (1)COX-2 selective inhibitors

■ Consider in patients who may be at high risk of developing serious GI adverse events, and in whom an NSAID is clearly indicated10

See over for updated Cox-2 prescribing guidelines

Management option 7 (1a)COX-2 selective inhibitors

■ High-risk patients include, those: aged 65 years and over, with a previous clinical history of gastroduodenal

ulcer, GI bleeding or gastroduodenal perforation. The use of even a COX-2 selective agent should be considered especially carefully in this situation,

taking concomitant medication(s) that are known to increase the likelihood of upper GI adverse events (eg corticosteroids, anti-coagulants)

24Please see Full Prescribing Information available at this presentation.

Management option 7 (2)COX-2 selective inhibitors June 2005 – The European Medicines Agency reviewed

Cox-2 selective inhibitors, they concluded that:

– the risks of potential fatal skin reactions with Valdecoxib (Bextra) outweighed the benefits and suspended Valdecoxib for a year, pending a review. Pfizer voluntarily withdrew Valdecoxib

– other Cox-2 selective inhibitors (Celecoxib, Etoricoxib, Lumiracoxib, Parecoxib) will have stronger guidelines for prescription:– Cox-2s should not be prescribed to people with ischaemic heart

disease, cerebrovascular disease or peripheral arterial disease– caution when prescribing Cox-2s to people with heart disease,

hypertension, hyperlipidaemia (cholesterol), diabetes and smokers

– doctors are advised to prescribe the lowest effective Cox-2 dose for the shortest possible duration

Celecoxib Efficacy in Osteoarthritis

McKenna F et al. Scand J Rheumatol 2001;30:11–18.VAS=visual analogue scale.

Less

Pai

n

Patient’s Assessment of Pain (VAS): Mean change at week 6

Mea

n C

hang

e (m

m)

*p=0.001 vs. placebo

placebo(n=200)

celecoxib100 mg BID(n=199)

diclofenac50 mg TID(n=199)

CELECOXIB vs. diclofenac:6-week Knee OA TrialMcKenna et al. 2001: Patient’s Assessment of Pain

McKenna F et al. Scand J Rheumatol. 2001;30:11-18.

American Pain Society (APS) Pain Measure:Worst Pain in the Past 24 Hours

Mea

n Ch

ange

in S

core p=0.05, active treatment vs.

placebo (days 1-7).

-4.0

-3.5

-3.0

-2.5

-2.0

-1.5

-1.0

-0.5

0.0Baseline Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7

placebo (n=200)celecoxib 100 mg BID (n=199)diclofenac 50 mg TID (n=199)

Less

Pai

nCELECOXIB vs. diclofenac:6-week Knee OA TrialMcKenna et al. 2001: American Pain Society – Pain Measure

CelecoxibGastrointestinal Safety Profile

Guidelines for Prevention of NSAID-Related Ulcer Complications(ACG Practice Guidelines 2009)

Lanza FL et al. Am J Gastroenterol 2009;104:728-738

CelecoxibCardiovascular Safety

Boxed Warning for All Prescription NSAIDs

Cardiovascular RiskNSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk. [Product] is contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.

Gastrointestinal Risk NSAIDs, including [product], cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal (GI) events.

09/25/09

APTC Composite End Point (Adjudicated): Celecoxib vs ns-NSAIDs

Meta-analysis of 25 RCTs

White et al. Am J Cardiol. 2007.

Rel

ativ

e R

isk

(CI)

of S

erio

us

CV

Adv

erse

Eve

nts

ns-NSAIDs(n=13,990)

Celecoxib 200-800 mg daily(n=19,773)

0.90(95% CI: 0.60-1.33)

2.0

1.5

0.5

0

1.01.0

49 events54 events

P =.59 (NS)

CELECOXIB vs. naproxen & etoricoxib:CV Safety ProfileSchwartz et al. 2007: Blood pressure change

Compared to naproxen and etoricoxib, celecoxib only shows significant change compared to placebo. Meanwhile etoricoxib shows significant increase compared to placebo, baseline, and celecoxib and naproxen.+ Significantly different from placebo (P ≤ .05)* Significantly different from baseline (P ≤ .05), placebo (P ≤ .05), and naproxen and celecoxib (P < .03) Schwartz JI et al. J Clin Pharmacol 2007;47:1521-31.

++

*

+ +*

Average blood pressure over a 24-hour period between days 1-14

2.43.6

7.7

0123456789

Syst

olic

blo

od p

ress

ure,

mm

Hg

celecoxib 200 mg BID (n=21) naproxen 500 mg BID (n=21) etoricoxib 90 mg OD (n=21)

Moore RA et al. BMC Musculoskelet Disord 2007;8:73.

celecoxib – Annually, per 1,000 patients, there were:

•12 fewer upper GI complications•2 fewer fatal/non-fatal heart attacks or strokes

celecoxib

etoricoxib

lumiracoxib

all coxibs

Event rate difference (coxib-NSAID per 1000 per year)

Favours coxib Favours ns-NSAID

GI bleed differenceCV event dfifference

Coxibs vs. ns-NSAIDs: GI and CV Benefit/Risk ProfileMoore et al. 2007: GI and CV Event Rates

CelecoxibRenal & Hepar Safety Profile

Incidence of patients with treatment-related CV, renal, and hepatic AEs

1.71.1

4.15.2

0123456

CV / renal AE Hepatic AE

% P

atie

nts

celecoxib 200 mg OD diclofenac 50 mg BID

CELECOXIB vs. diclofenacDahlberg et al. 2009: CV / renal & hepatic AEs

One-year, randomized, multicentre, double-blind, parallel-group study to assess the AE-related discontinuation rate with celecoxib and diclofenac in elderly patients with OA.No p-values reported for related/not-related-to-treatment incidence. Significantly fewer patients in the celecoxib group than the diclofenac group experienced cardiovascular/renal AEs (70/458 vs. 95/458, p=0.039) or hepatic AEs (10/458 vs. 39/458, p<0.0001).Dahlberg LE et al. Scand J Rheumatol 2009;38:133-143.

Prevalence of hepatic events

0.24

0.97

0.590.5

0.370.31

0.21

0

0.2

0.4

0.6

0.8

1

1.2

% h

epat

ic e

vent

s celecoxibdiclofenacketoprofenmeloxicametodolacpiroxicamibuprofen

CELECOXIB vs ns-NSAIDs:Hepatic Safety ProfileSanchez-Matienzo et al. 2006: Prevalence of hepatic events

A case/noncase analysis of spontaneous reports was conducted to compare the hepatic safety profile of COXIBs and ns-NSAIDs.

Sanchez-Matienzo D et al. Clin Ther 2006;28:1123-1132.

Management option 8Symptomatic slow-acting drugs of OA■ Symptomatic slow-acting drugs of OA

(SYSADOA) glucosamine chondroitin hyaluronic acid diacerein

■ Supported by increasing evidence, although further research is still required5,8,11,12

■ Given that these agents appear to be well tolerated and do show some benefit their use should be considered13

Management option 9Corticosteroid injections

■ Corticosteroid intra-articular injections may be used in the management of patients with OA of the knee5

■ Provide superior short-term efficacy (2-4 weeks) versus placebo8

■ Recommended for acute exacerbations5

Management option 10Surgery

■ Refer for orthopaedic evaluation if patient is disabled by OA or in pain unrelieved by medical management5,9

■ Joint replacement can be very effective5

■ Newer techniques such as metal-on-metal resurfacing are less invasive15

■ Patients should be made aware of the risks and benefits of surgery

Other useful resources

Arthritis Research Campaign http://www.arc.org.uk

Primary Care Rheumatology Societyhttp://www.pcrsociety.com

British Society for Rheumatologyhttp://www.rheumatology.org.uk

The European League Against Rheumatismhttp://www.eular.org

National Library for Health – Musculoskeletal Libraryhttp://libraries.nelh.nhs.uk/musculoskeletal

Primary Care Question & Answer Servicehttp://www.clinicalanswers.nhs.uk/index.cfm

References 1-9

1. Arthritis Care. 1 in 5 – The prevalence and impact of arthritis in the UK (Research report). February 2002.2. Disability Care and Mobility Quarterly Statistical Enquiry - Disability Living Allowance, Attendance Allowance

and Invalid Care Allowance. Dept of Work and Pensions 2002.3. Watson M. Management of patients with osteoarthritis. Pharm J 1997;259:296-297.4. Royal College of General Practitioners OPCS Department of Health and Social Security. Morbidity statistics

from General Practice. Fourth National Survey 1991-1992. HMSO, 1996. 5. Jordan KM, Arden NK, Doherty M et al. EULAR recommendations 2003: an evidence based approach to the

management of knee osteoarthritis: Report of a task force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Ann Rheum Dis 2003;62:1145-1155.

6. Dawson J, Fitzpatrick R, Murray D et al. Questionnaire on the perceptions of patients about total knee replacement. J Bone Joint Surg (Br) 1998;80:63-69.

7. Creamer P, Lethbridge-Cejku M, Hochberg MC. Factors associated with functional impairment in symptomatic knee osteoarthritis. Rheumatology 2000;39:490-496.

8. Walker-Bone K, Javaid K, Arden N et al. Regular review: Medical management of osteoarthritis. BMJ 2000;321:936-940.

9. Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Arthritis Rheum 2000;43(9):1905-1915.

References 10-15

10. Guidance on the use of cyclo-oxygenase (COX) II selective inhibitors, celecoxib, rofecoxib, meloxicam and etodolac for osteoarthritis and rheumatoid arthritis. NICE Technology Appraisal Guidance 27, July 2001.

11. Deal CL, Moskowitz RW. Nutraceuticals as therapeutic agents in osteoarthritis. The role of glucosamine, chondroitin sulfate and collagen hydrolysate. Rheum Clin N Am 1999;25:379-395

12. Is glucosamine worth taking for osteoarthritis. Drug & Ther Bull 2002;40:81-83.13. Chard J, Dieppe P. Glucosamine for osteoarthritis: Magic, hype, or confusion? It's

probably safe-but there's no good evidence that it works. BMJ 2001;322(7300):1439-1440.

14. Guidance on the selection of prostheses for primary total hip replacement. NICE Technology Appraisal Guidance 2, April 2000.

15. Guidance on the use of metal on metal hip resurfacing arthroplasty. NICE Technology Appraisal Guidance 44, June 2002.

46Please see Full Prescribing Information available at this presentation.

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