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 limitation 1
Affects more women than men in every age group 2
(%)
Adults (%)
Arthritis
With Arthritis
US Adults
With
US

Age Group, years

Arthritis and rheumatism leading causes of disability in US3

By 2030, a projected 67 million in US will have HCP-diagnosed arthritis4
* 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.
 Osteoarthritis: burden of disease

One in five people in the UK have arthritis 1

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 disability 3
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
Obesity Aging

Anatomic
abnormalities Genetic and
metabolic
Microfractures diseases
and bony Abnormal stresses Abnormal cartilage
remodeling Inflammation
Loss of joint
stability Immune
Compromised cartilage system
Trauma activity

Biophysical changes Biochemical changes

Collagen network fracture Inhibitors reduced
Proteoglycan unraveling Proteolytic enzymes increased

Cartilage breakdown

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

Symptoms
1 Persistent knee pain
2 Limited morning stiffness
3 Reduced function
Signs
4 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:
Presence of 3 of the following
1 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

Sensitivity, 95%; specificity, 69%

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 patient

2. The relationship between the healthcare team
and the patient should be a two-way process
3. Using tools can help to assess the patients pain
and disability
4. Patient education has a significant impact on
pain management
5. 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 1
Patient-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 patients 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 patients 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 symbol
Mark the areas of radiation
Include all affected areas

Numbness ====
Pins and needles
Burning xxxxxxxx
Stabbing ///////
Rating scales

Visual analogue scale

No Worst
pain 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

Maintain and
improve joint
mobility
Reduce Reduce
joint pain and physical
stiffness disability
Knee and Hip OA:
Goals of
Treatment
Improve Educate
HRQoL patients
Limit
progression of
joint damage

HRQoL=health-related quality of life; OARSI=Osteoarthritis Research Society International.

Zhang W et al. Osteoarthritis Cartilage. 2008;16(2):137-162.
 Integrated Approach to Treating Patients With OA
Nonpharmacologic Pharmacologic
Patient education APAP
Phone contact (promote self-care) Oral NSAIDs
Referral to physical therapist Topical NSAIDs and capsaicin
Aerobic, strengthening, and/or water- Corticosteroid injections
based exercise Hyaluronate injections
Weight reduction Glucosamine, chondroitin sulphate,
Walking aids, knee braces and/or diacerein
Proper footwear, insoles Weak opioids and narcotic analgesics
Thermal modalities for refractory pain*
TENS
Acupuncture

Surgical
Total joint replacement Lavage/debridement in knee OA
Unicompartmental knee replacement Joint fusion after failure of joint
Osteotomy and other joint preserving replacement
surgical procedures

* Pain resistant to ordinary treatment. Controversial.

TENS=transcutaneous electrical nerve stimulation.
Zhang W et al. Osteoarthritis Cartilage. 2008;16(2):137-162.
Management option 6
Non-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:
Acupuncture
Alexander technique
Aromatherapy
Chiropractice
Hydrotherapy Massage
Osteopathy
Reflexology
Tai 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 7
Analgesia and NSAIDs
Use paracetamol as first-line therapy 5
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 events 10
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)

24
Please 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
CELECOXIB vs. diclofenac:
6-week Knee OA Trial
McKenna et al. 2001: Patients Assessment of Pain
Patients Assessment of Pain (VAS): Mean
change at week 6 *p=0.001 vs. placebo
Mean Change (mm)
Less Pain

placebo celecoxib diclofenac

(n=200) 100 mg BID 50 mg TID
(n=199) (n=199)

VAS=visual analogue scale.

McKenna F et al. Scand J Rheumatol 2001;30:1118.
CELECOXIB vs. diclofenac:
6-week Knee OA Trial
McKenna et al. 2001: American Pain Society Pain
Measure
American Pain Society (APS) Pain Measure:
Worst Pain in the Past 24 Hours
Baseline Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7
0.0
Mean Change in Score

-0.5
p=0.05, active treatment vs.
placebo (days 1-7).
-1.0
Less Pain

-1.5

-2.0

-2.5

-3.0
placebo (n=200)
-3.5
celecoxib 100 mg BID (n=199)

-4.0 diclofenac 50 mg TID (n=199)

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

 Celecoxib
Gastrointestinal Safety Profile
 Guidelines for Prevention of
NSAID-Related Ulcer Complications
(ACG Practice Guidelines 2009)

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

 Celecoxib
Cardiovascular Safety
Boxed Warning for All Prescription NSAIDs

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 APTC Composite End Point (Adjudicated):
Celecoxib vs ns-NSAIDs
Meta-analysis of 25 RCTs
2.0

P =.59 (NS)
Relative Risk (CI) of Serious

1.5
CV Adverse Events

1.0 0.90
1.0 (95% CI: 0.60-1.33)
49 events
54 events

0.5

0
ns-NSAIDs Celecoxib 200-800 mg daily
(n=13,990) (n=19,773)

White et al. Am J Cardiol. 2007. 09/25/09

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

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

9
7.7
Systolic blood pressure, mm Hg

8
7
6
5 *
4 3.6
3 2.4 *
2 ++
+
+
1
0
celecoxib 200 mg BID (n=21) naproxen 500 mg BID (n=21) etoricoxib 90 mg OD (n=21)
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.
Coxibs vs. ns-NSAIDs: GI and CV Benefit/Risk Profile
Moore et al. 2007: GI and CV Event Rates

Favours coxib Favours ns-NSAID

celecoxib

etoricoxib

lumiracoxib

all coxibs

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

celecoxib Annually, per 1,000 patients, GI bleed difference

CV event dfifference
there were:
12 fewer upper GI complications
2 fewer fatal/non-fatal heart attacks or strokes
Moore RA et al. BMC Musculoskelet Disord 2007;8:73.
 Celecoxib
Renal & Hepar Safety Profile
 CELECOXIB vs. diclofenac
Dahlberg 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.
CELECOXIB vs ns-NSAIDs:Hepatic Safety Profile
Sanchez-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 8
Symptomatic 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 9
Corticosteroid 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 exacerbations 5
Management option 10
Surgery

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 Society
http://www.pcrsociety.com
British Society for Rheumatology
http://www.rheumatology.org.uk
The European League Against Rheumatism
http://www.eular.org
National Library for Health Musculoskeletal Library
http://libraries.nelh.nhs.uk/musculoskeletal
Primary Care Question & Answer Service
http://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.
 THANK YOU

46
Please see Full Prescribing Information available at this presentation.