Rheumatoid Arthritis: Learn and Take Action

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Rheumatoid ArthritisLearn and Take Action

• Harbor Hospital Arthritis and Osteoporosis Center
• The Arthritis Foundation

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Learn
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What Is Rheumatoid Arthritis (RA)?

• RA is a condition involving inflammation of the
  joints1,2
• It has the potential to result in serious joint
  damage1,2
• It may come on suddenly or appear slowly over
  time1,2
• Its symptoms may include pain, swelling,
  stiffness in the joints, and general tiredness1,2

References 1. Beers MH, et al, eds. The Merck
Manual of Diagnosis and Therapy. 17th ed.
Whitehouse Station, NJ Merck Research
Laboratories 1999416,419. 2. Rosenberg AE. In
Cotran RS, et al, eds. Robbins Pathologic Basis
of Disease. 5th ed. Philadelphia, Pa W.B.
Saunders Company 19941249,1252.
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Who Gets RA?

• RA is one of the most common forms of
  inflammatory arthritis1
• Affects about 1 of the worlds population1,2
• Occurs 2 to 3 times more often in women than in
  men1
• In most cases it develops between the ages of 25
  and 501

References 1. Beers MH, et al, eds. The Merck
Manual of Diagnosis and Therapy. 17th ed.
Whitehouse Station, NJ Merck Research
Laboratories 1999416,479. 2. Rosenberg AE. In
Cotran RS, et al, eds. Robbins Pathologic Basis
of Disease. 5th ed. Philadelphia, Pa W.B.
Saunders Company 19941249.
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What Causes RA?

• RA is a disease of the immune system, the system
  that normally protects your body against foreign
  invaders such as bacteria, fungi, and viruses1,2

References 1. Beers MH, et al, eds. The Merck
Manual of Diagnosis and Therapy. 17th ed.
Whitehouse Station, NJ Merck Research
Laboratories 1999416. 2. Rosenberg AE. In
Cotran RS, et al, eds. Robbins Pathologic Basis
of Disease. 5th ed. Philadelphia, Pa W.B.
Saunders Company 19941249.
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The Immune Process

• Inflammation is commonly triggered to protect the
  body and destroy foreign invaders1
• The inflammation process is controlled in part by
  chemical messengers called cytokines2
• One of these cytokines is tumor necrosis factor
  (TNF)2

References 1. Carpenter AB. In Wegener ST, et
al, eds. Clinical Care in the Rheumatic Diseases.
Atlanta, Ga American College of Rheumatology
199611-12. 2. Moreland LW, et al. N Engl J Med.
1997337141-147.
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The Immune Process in RA

• With RA, the immune system loses some of its
  ability to tell the
• difference between foreign invaders and the
  bodys normal cells1
• As a result, the immune system begins to attack
  the bodys cells
• This causes inflammation in the joints

References 1. Arthritis Foundation. The
Arthritis Foundations Guide to Good Living With
Rheumatoid Arthritis. Atlanta, Ga Arthritis
Foundation 200210,12.
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What Can Happen When You Have RA?
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Signs and Symptoms of RA

• Tender, warm, swollen joints1
• Symmetrical pattern (for example, if one knee is
  affected, the other one is also)2
• Often affects the wrist and finger joints of the
  hand1,2
• Fatigue, occasional fever, general sense of not
  feeling well1
• Symptoms in other parts of the body besides the
  joints (nodules in or under the skin, lung
  scarring, eye inflammation)1
• Pain and stiffness in the morning commonly
  lasting more than 30 minutes1

References 1. Arthritis Foundation. The
Arthritis Foundations Guide to Good Living With
Rheumatoid Arthritis. Atlanta, Ga Arthritis
Foundation 200210,14. 2. Klippel JH, ed. Primer
on the Rheumatic Diseases. 12th ed. Atlanta, Ga
Arthritis Foundation 2001632.
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Joint Damage in RA
Loss of Function Increases
Early
Intermediate
Late
Photograph courtesy of Lester Miller, M.D.,
Santa Cruz, Calif.
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Increased Joint Damage Affects Day-to-Day
Activities1

• As joint damage progresses, RA can begin to
  affect many different areas of life. Each
  individual is different, but as the disease
  progresses, the ability to function can
  decrease.1
• Activities that may be affected are1
• Dressing
• Bathing
• Walking
• Running errands

Reference 1. Arthritis Foundation. The Arthritis
Foundations Guide to Good Living With Rheumatoid
Arthritis. Atlanta, Ga Arthritis Foundation
200254.
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People With RA May Be at Increased Risk of Work
Disability

• Studies in the last 2 decades showed that during
  the first 2 to 3 years of RA, 20 to 30 of
  patients became work-disabled1
• Studies also showed that more than 50 of
  patients were disabled during the first 10 years
  of the disease1

Reference 1. Sokka T. Clin Exp Rheumatol.
200321(suppl 31)S71-S74.
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Discussion

• Common Signs and Symptoms of RA
• Questions to ask yourself
• Are you experiencing pain and stiffness in your
  joints?
• Do you frequently feel tired?
• Do you have trouble with daily activities such as
  brushing teeth, tying shoes, opening jars, etc.,
  because of pain?
• Do you have difficulty doing the things you
  normally like to do such as gardening, shopping,
  and family activities, etc.?

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Take Action
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Importance of Acting Early

• You dont have to live with the pain and fatigue
  of RAproper treatments may help1-3
• Acting early can slow joint destruction4
• According to one study, some patients had joint
  damage at their first doctor visit5
• Joint erosion can start in less than 2 years6

References 1. Klareskog L, et al. Lancet.
2004363675-681. 2. Breedveld FC, et al. Ann
Rheum Dis. 200463149-155. 3. Wiles NJ, et al.
Arthritis Rheum. 2001441033-1042. 4. Enbrel
(etanercept) Prescribing Information, Immunex
Corporation, Thousand Oaks, Calif. 5. van der
Horst-Bruinsma IE, et al. Br J Rheumatol.
1998371084-1088. 6. van der Heijde DM, et al.
Br J Rheumatol. 199534(suppl 2)74-78.
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Diagnosing RA
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See a Doctor Right Away

• If you think you may have RA, see a doctor for
  diagnosis
• Talk to your family doctor about referring you to
  a rheumatologist
• A rheumatologist is a doctor specially trained in
  treating RA and other forms of arthritis1
• Your family doctor and your rheumatologist can
  work together to ensure you get the best possible
  care

Reference 1. Arthritis Foundation. The Arthritis
Foundations Guide to Good Living With Rheumatoid
Arthritis. Atlanta, Ga Arthritis Foundation
200260.
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Confirming a Diagnosis of RA

• Medical history and physical examination1
• Laboratory tests1
• Imaging tests (x-rays, etc.)1

Reference 1. Arthritis Foundation. The Arthritis
Foundations Guide to Good Living With Rheumatoid
Arthritis. Atlanta, Ga Arthritis Foundation
200254-56.
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Medical History and Physical Examination

• General Complaints1
• Fatigue and morning stiffness
• Joint-Related Complaints1
• Pain in movement
• Pain at rest
• Swelling of joints
• Loss of range of movement
• Grip strength
• Physical Examination1
• The physical examination is the first step in
  confirming a diagnosis

Reference 1. Arthritis Foundation. The Arthritis
Foundations Guide to Good Living With Rheumatoid
Arthritis. Atlanta, Ga Arthritis Foundation
200220,22.
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Common Laboratory Tests

• Laboratory tests can help support the diagnosis
  of RA1
• Rheumatoid factor1
• Erythrocyte sedimentation rate (ESR), or sed
  rate1
• C-reactive protein (CRP)1
• Anemia (low red blood cells RBCs)1

Reference 1. Arthritis Foundation. The Arthritis
Foundations Guide to Good Living With Rheumatoid
Arthritis. Atlanta, Ga Arthritis Foundation
200224-25.
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Imaging Tests

• Imaging tests may be helpful in diagnosing RA and
  determining whether the disease is progressing1
• X-rays (radiographs)1
• Magnetic resonance imaging (MRI)1
• Ultrasound1

Radiograph courtesy of C. Michael Franklin, M.D.,
Willow Grove, Pa.
Reference 1. Arthritis Foundation. The Arthritis
Foundations Guide to Good Living With Rheumatoid
Arthritis. Atlanta, Ga Arthritis Foundation
200255-56.
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Treating RA
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Action Steps

• Periods of activity balanced with periods of
  rest1
• Appropriate exercise1
• Management of stress1
• Patient and caregiver support services
• Medications

Reference 1. Arthritis Foundation. The Arthritis
Foundations Guide to Good Living With Rheumatoid
Arthritis. Atlanta, Ga Arthritis Foundation
2002119,135,150-160.
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Medications for RA

• Nonsteroidal anti-inflammatory drugs (NSAIDs)1,2
• Corticosteroids (steroids)2
• Disease-modifying antirheumatic drugs (DMARDs)1,2
• Biologics2
• Combination of any of the above therapies1

References 1. Arthritis Foundation. The
Arthritis Foundations Guide to Good Living With
Rheumatoid Arthritis. Atlanta, Ga Arthritis
Foundation 200275-76,96. 2. ODell JR. N Engl J
Med. 20043502591-2602.
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NSAIDs Reduce Pain and Inflammation

• NSAIDs can help relieve not only pain but
  inflammation as well1,2
• NSAIDs have not been shown to slow the joint
  destruction of RA2
• Side effects may include stomach problems, such
  as ulcers1,2
• Examples of NSAIDs Advil, Motrin (ibuprofen)
  Bayer (aspirin)
• Celebrex (celecoxib)

References 1. Arthritis Foundation. The
Arthritis Foundations Guide to Good Living With
Rheumatoid Arthritis. Atlanta, Ga Arthritis
Foundation 200277,99-100,102. 2. ODell JR. N
Engl J Med. 20043502591-2602.
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Corticosteroids Reduce Inflammation

• Corticosteroids can provide short-term relief of
  inflammation, leading to less pain and swelling1
• Side effects may include blood sugar elevation,
  cataracts, hypertension, increased infections and
  bruising, osteoporosis, and weight gain1,2
• Examples of corticosteroids Deltasone, Orasone
  (prednisone) Hydrocortone (hydrocortisone)

References 1. ODell JR. N Engl J Med.
20043502591-2602. 2. Arthritis Foundation. The
Arthritis Foundations Guide to Good Living With
Rheumatoid Arthritis. Atlanta, Ga Arthritis
Foundation 200284,103-104.
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DMARDs Can Slow the Joint Destruction of RA

• DMARDs can help
• Relieve pain and stiffness1
• Slow the progression of joint destruction1
• Side effects, depending on the treatment, may
  include diarrhea, eye damage, liver damage,
  nausea, and vomiting1,2
• Examples of DMARDs Arava (leflunomide)
  Azulfidine EN-Tabs
• (sulfasalazine) Rheumatrex (methotrexate MTX)

References 1. ODell JR. N Engl J Med.
20043502591-2602. 2. Arthritis Foundation. The
Arthritis Foundations Guide to Good Living With
Rheumatoid Arthritis. Atlanta, Ga Arthritis
Foundation 2002104-106.
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Biologic Therapy

• Recently, research has led to breakthrough
  therapies known as biologics, biologic therapies,
  or biologic response modifiers (BRMs)1
• Some biologic therapies target the immune system
  by blocking cytokines (such as TNF) that cause
  inflammation2-4
• Biologics must be administered by
  injection/infusion4
• Side effects depending on the treatment may
  include injection site reaction, infection, and
  headache4

References 1. ODell JR. N Engl J Med.
20043502591-2602. 2. Klareskog L, et al.
Lancet. 2004363675-681. 3. Breedveld FC, et
al. Ann Rheum Dis. 200463149-155. 4. Arthritis
Foundation. The Arthritis Foundations Guide to
Good Living With Rheumatoid Arthritis. Atlanta,
Ga Arthritis Foundation 200295-96.
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TNF Plays a Key Role in the Inflammation and
Joint Damage Seen in RA

• TNF binds to receptors on a variety of cells,
  activating them and initiating a cascade of
  inflammatory events1
• The body can normally regulate excess TNF levels
  except when the immune system is functioning
  abnormally, as in RA2

References 1. Shlotzhauer TL, McGuire JL. Living
With Rheumatoid Arthritis. 2nd ed. Baltimore, Md
The Johns Hopkins University Press 200313,15.
2. Choy EHS, et al. N Engl J Med.
2001344907-916.
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TNF BlockersChanging the Way We Treat RA

• TNF blockers are able to attach to TNF and help
  block the process that leads to the pain,
  inflammation, and joint damage of RA1
• TNF blockers target your immune system to help2
• Control symptoms (for example, pain, stiffness,
  swelling, and fatigue)
• Slow the progression of joint damage
• Improve function
• Examples of TNF blockers Enbrel (etanercept)
  Humira
• (adalimumab) Remicade (infliximab)

References 1. ODell JR. N Engl J Med.
20043502591-2602. 2. Choy EHS, et al. N Engl J
Med. 2001344907-916.
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Evolution of TNF Blocking Therapies

• Etanercept Infliximab Adalimumab
• Characteristic (ENBREL?) (REMICADE?)
  (HUMIRA)
• Class sTNFR TNF MAb TNF MAb
• Construct Recombinant Chimeric MAb Recombinant
• fusion protein human MAb
• Half-life 4 days 810 days 1020 days
• Binding target TNF/LT? TNF TNF
• Administration 25 mg 310 mg/kg 40 mg
• SC IV with MTX SC
• Twice weekly Every 48 weeks Every other
  week

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Side Effects of Common Drugs

• Serious infection
• Opportunistic infection, i.e. tuberculosis
• Lymphoproliferative Disorder
• Demyelinating Disease
• Hematologic Disease
• Administration Complications
• Malignancies
• Congestive Heart Failure

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Indications
Enbrel Remicade Humira

• Adult RA Adult RA Adult RA
• JRA AS Crohns Disease
• AS Crohns Disease Psoriasis
• Psoriatic Arthritis Psoriasis Psoriatic
  Arthritis
• Psoriasis Psoriatic Arthritis JRA

with the FDA
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Questions to Ask Your Doctor About What Treatment
Is Right for You

• If you are deciding whether or not to try a
  treatment
• What are the possible benefits of taking this
  medicationand when should I notice them?
• How long has this product been on the market?
• What are its side effects?
• How is it given?

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Questions to Ask Your Doctor About What Treatment
Is Right for You (contd)

• If you are already on treatment
• How can I tell if the treatment is working?
• Are there other treatment options that might help
  me more than my current treatment?
• How can I tell if my disease is progressing?
• How often will I need x-rays or tests to monitor
  how Im doing?

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Resources for More Information

• Your doctor
• www.arthritis.org
• Arthritis Foundation
• www.rheumatology.org
• American College of Rheumatology
• www.rheummates.com
• Amgen and Wyeth Pharmaceuticals
• www.enbrel.com
• Amgen and Wyeth Pharmaceuticals
• www.humira.com
• Abbott Pharmaceuticals
• www.remicade.com
• Centocor Pharmaceuticals

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The COX-2 Controversy
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COX-2s, NSAIDs and Cardiovascular Risk

• September 2000 VIGOR (Vioxx Gastrointestinal
  Outcomes Research Study)
• Rheumatoid patients Rofecoxib vs. Naproxen
• 5x increase CV events
• September 2004 Company-sponsored trial
• 2600 patients, FAP (Familial Adenomatous
  Polyp)
• 2x increase CV events
• (data not published)
• RESULT Rofecoxib (Vioxx) voluntary withdrawal
  from the market
• December 2004 FDA announces NEW warning for
  valdecoxib (Bextra) related to CV risks

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2004 Long-Term Trials and their Findings
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2004 Long-Term Trials and their Findings (cont.)
All three trials have been suspended
FDA Advisory Panel met in D.C. from Feb. 24 Feb.
26, recommending that Celebrex and Bextra remain
on the market and Voixx be brought back to the
market, with restriction. The final decision will
be made by the FDA in the coming months.
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Thank You!