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					    RHEUMATOID ARTHRITIS
          WHAT‟S NEW
          WHAT‟S “HIP”
HOW DO THE ALGORITHMS SHAPE UP?

      DR. CHRISTOPHER LYDDELL
            Rheumatologist
                            RHEUMATOID ARTHRITIS

                              Epidemiology
      – Affects approximately 1% of the global adult
        population
      – Estimated annual incidence
         • Males: 0.1–0.2 per 1000
         • Females: 0.2–0.4 per 1000
      – Occurs 2 to 3 times more often in women than
        in men
      – Incidence largely consistent racially and
        geographically
      – Peak age of onset between the ages of 45 and
        65 years
Sangha O. Rheumatology. 2000;39(suppl 2):3–12.
MacGregor AJ, Silman AJ. In: Klippel JH, Dieppe PA, eds. Rheumatology. Vol 1. 2nd ed. London:
Mosby;1998:2.1–2.6.
             RHEUMATOID ARTHRITIS

       Worldwide Incidence and Prevalence
                                              Prevalence (per 100)
W. Europeans/                                            0.8–1.1
 North Americans (Whites)
Chinese                                                  0.3–0.4
Amerindians (Chippewa, Pima)                               5–8

                                           Incidence (per 1000/year)
                                              Women             Men
W. Europeans/                                0.24–3.34     0.1–1.50

 North Americans (Whites)
Maini RN. Acta Orthop Scand Suppl. 1998;281:6–13.
           RHEUMATOID ARTHRITIS
Social and Psychological Burden
– Patients usually experience moderate disability
  within
  2 years of diagnosis and are severely disabled by 10
  years
– Approximately 30% of patients are unable to work
  within
  10 years of RA onset
– Patients experience feelings of helplessness and
  other psychological distress due to their increasing
  dependence upon help from others
– Patients may be prevented from carrying out social
  roles
               Alarcón GS. Rheum Dis Clin North Am. 1995;21:589–604.
                Wolfe F, Hawley D. J Rheumatol. 1998;25:2108–2117.
                       Pincus T. Drugs. 1995;50(suppl 1):1–14.
   Rheumatoid Arthritis: Employment

100%   100%

80%
                60%
60%                         50%

40%                                  33%

20%

 0%
        0        5           10      15

              Disease Duration (Y)
                        RHEUMATOID ARTHRITIS
                Economic Burden (US)
    – Estimated costs of RA were $8.74 billion in 1994,
      0.3% of the gross domestic product (GDP)
    – Direct medical costs are $5,919/case/year
    – Indirect costs
        • 3 to 4 times higher than direct costs
        • $11,750 per person-year in patients with early RA
    – Lifetime costs of RA rival those of coronary artery
      disease or stroke



Yelin E. J Rheumatol Suppl. 1996;44:47–61.
Yelin E, Wanke LA. Arthritis Rheum. 1999;42:1209–1218.
Allaire SH et al. Pharmacoeconomics. 1994;6:513–522.
Merkesdal S et al. Arthritis Rheum. 2001;44:528–534.
                                       RHEUMATOID ARTHRITIS
                   Economic Burden (Europe)
       – In West Germany, the costs of RA were >40 billion
         DM
         (US $17.6 billion) in 1994 for treatment alone
       – In the UK, average RA outpatient cost/case/year was
         £798
         (US $1,126) and £1,253 (US $1,769) per inpatient in
         1997
       – RA per capita costs average:
          • 49% of cost of cancer
          • 68% of cost of stroke
          • 82% of cost of coronary heart disease
          • 5X cost of motor vehicle accidents
Knorr U. Versicherungsmedizin. 1994.
Rothfuss J. Akt Rheumatol. 1997.
Lubeck DP et al. Arthritis Rheum. 1986;29:488–493.
Lorig KR et al. Arthritis Rheum. 1993;36:439–446.
Economic burden in SA????
    Diagnosis of Rheumatoid Arthritis
    American College of Rheumatology
                 Criteria
    At least 4 of the following
      criteria
    – Morning stiffness >1 hour
    – Arthritis of 3 joint areas                    Must be present
                                                     for at least 6 weeks
    – Arthritis of hand joints
    – Symmetric arthritis
    – Rheumatoid nodules
    – Serum rheumatoid factor
    – Radiographic changes

Arnett FC et al. Arthritis Rheum. 1988;31:315–324.
                        RHEUMATOID ARTHRITIS
                         Clinical Course
– Clinical course unpredictable but mostly progressive
– Unfavorable prognostic markers
  – Male sex                      – Eosinophilia
  – Low socioeconomic status – Elevated ESR or CRP
  – Subcutaneous nodules          – High RF factor titer
  – Systemic signs                – Antinuclear antibodies
  – Persistent synovitis          – Cryoglobulins
  – Thrombocytosis                – Shared epitope (?)
  - Anti CCP
– Disease activity reduced faster and radiographic evidence of
  joint damage lessened with early diagnosis and treatment

Albers JMC et al. Ann Rheum Dis. 2001;60:453–458.
Grassi W et al. Eur J Radiol. 1998;27(suppl 1):S18–S24.
                            Clinical Courses of RA




Adapted from: Henderson, Edwards, Pettipher. Mechanisms and Models in Rheumatoid Arthritis.
© 1995 Academic Press Limited.
                                            RHEUMATOID ARTHRITIS
                                  Radiologic Features

         – Early stage
                  • Soft tissue swelling
         – Intermediate stage
                  • Mild juxtaarticular
                    osteoporosis
                  • Narrowing of joint
                    space
                    and bone erosions
         – Late stage
                  • Large erosions,
                    anatomic deformities,
                    ankylosis
Bower AC. In: Klippel JH, Dieppe PA, eds. Rheumatology.
Vol 1. 2nd ed. Philadelphia, PA: WB Saunders; 1998;5:5.1–5.8.
Resnick D et al. In: Kelley WN et al, eds. Textbook of Rheumatology. 5th ed. Philadelphia, PA: WB Saunders; 1997:626–685.
             Erosions Occur Early in RA

    Time           % with Erosions Reference

    <3 months               26           Harrison et al. Arthritis
      Rheum; 2000.

    1 year (9 months) 62                Proudman. Arthritis Rheum;
      2000.
*   2 years           75                van der Heijde. Br J
      Rheumatol; 1995.

    2 years (4 months) 77               Boers et al. Lancet; 1997.

    2 years (9 months) 68               Peltomaa et al. J Rheum;
      2000.
    *At 2 years, 73% ± 5% of RA patients have erosions.
          X-ray Scoring Systems

• Sharp method (and its modifications)
  – Detailed scoring of erosions and joint
    space narrowing


• Larsen method (and its modifications)
  – Global grading based mainly on erosions
          Modified Sharp Scoring Method

                                      Total Sharp Score = JSN + JE
         = Joint space narrowing (JSN)                              Joint erosions (JE)




         40 joints evaluated                                     44 joints evaluated

             Scoring:                                            Scoring:
             0 = normal                                          1 = discrete
             1 = focal or doubtful                               2-4 = depending on surface area involved
             2 = >50% of original space left                     5 = complete collapse
             3 = <50% of joint space or subluxation
             4 = bony ankylosis or luxation

van der Heijde DM. Baillieres Clin Rheumatol. 1996;10:435-453.
RA Results in Significantly Decreased
          Life Expectancy
 5-year survival 45%–55% for patients with
  unfavorable profiles
 Comparable to 3-vessel CAD or
  Stage IV Hodgkin’s disease
 Standardized mortality ratio: 1.16-7x
 Life expectancy decreased by 3–10 years
 Increased mortality with worsening HAQ
Extra-articular RA
    Vasculitis
Extraarticular RA
    The Eye
Rheumatoid-the long term!
                                 Very Early Treatment With Infliximab in Addition to
                             Methotrexate in Early, Poor-Prognosis Rheumatoid Arthritis
                                Reduces Magnetic Resonance Imaging Evidence of
                                   Synovitis and Damage, With Sustained Benefit
                                             After Infliximab Withdrawal
                              Results From a Twelve-Month Randomized, Double-Blind,
                                              Placebo-Controlled Trial
                                                      Emery et al


                           “Rheumatoid arthritis (RA) is the most common,
                        potentially treatable cause of disability in the western
                world (1). Evidence supports the early use of disease modifying
                                 Antirheumatic drugs (DMARDs) in RA;
                      however, the optimal treatment strategy is uncertain (2).
                  Ideally, effective therapy would produce rapid and sustained
                            suppression of inflammatory disease, resulting
                        in preserved function and prevention of joint damage,
                         without risk of long-term toxicity. A hypothesis in RA
                      research is that early in the disease process, a “window
                        of opportunity” exists, where therapeutic intervention
                       has a disproportionate impact on outcome (3–5). Proof
                           of this concept for an anti–tumor necrosis factor
                      (anti-TNF) agent would require maintenance of response
ARTHRITIS & RHEUMATISM                after cessation of treatment.”
Vol. 52, No. 1, January 2005, pp 27–35
DOI 10.1002/art.20712
© 2005, American College of Rheumatology
                  Combination of Infliximab and Methotrexate Therapy for
                               Early Rheumatoid Arthritis
                             A Randomized, Controlled Trial
                                                  Quinn et al




                              „This study has shown that patients with active RA
                           in its early stages can benefit from aggressive therapy
                              using a TNF inhibitor–based combination regimen.
                             However, these results also show that a significant
                         proportion of patients with early RA can achieve disease
                             control for 1 year by taking MTX alone. Thus, for the
                           individual patient, the potential incremental benefits of
                            the combination approach must be carefully weighed
                          against the possibility of greater toxicity. These results
                             nevertheless show that the combination of MTX and
                         infliximab produces clinical, radiographic, and functional
                                benefits exceeding those of MTX alone and may
                             ultimately prove to be a highly effective strategy for
                             preventing joint damage and functional disability in
                                 patients at high risk for disease progression.‟
ARTHRITIS & RHEUMATISM
Vol. 50, No. 11, November 2004, pp 3432–3443
DOI 10.1002/art.20568
© 2004, American College of Rheumatology
   Etanercept Versus Methotrexate in Patients With Early
                  Rheumatoid Arthritis
      Two-Year Radiographic and Clinical Outcomes
                                           Genovese et al


                                 “Etanercept and MTX had excellent
                     profiles for initial treatment of patients with active,erosive
                      RA. The benefits of 25-mg etanercept as monotherapy
                      were shown to be superior to those of MTX at 2years,
                           and improvements in clinical, radiographic, and
                       disability end points were maintained with sustained
                                                therapy.”




ARTHRITIS & RHEUMATISM
Vol. 46, No. 6, June 2002, pp 1443–1450
DOI 10.1002/art.10308
© 2002, American College of Rheumatology
                        TREATMENT OF RHEUMATOID ARTHRITIS
               Measurement of Treatment Effects
           – Clinical assessment of –                     Assessment of physical
             inflammatory synovitis                       function
             • Swollen joint count,                       • Stanford Health
               tender joint count                           Assessment
           – Laboratory assessment                          Questionnaire (HAQ)
             of inflammatory synovitis                    • Short-Form 36 Health
             • Acute phase reactants                        Survey
               (eg, ESR, CRP)                               (SF-36)
                                      –                   Assessment of structural
                                                          joint
                                                          damage
ACR ad hoc Committee on Clinical Guidelines.              • Radiography (ultrasound
Arthritis Rheum. 1996;39:713–722.                           and magnetic resonance
Grassi W et al. Eur J Radiol. 1998;27(suppl 1):S18–S24.
                                                            imaging)
         TREATMENT OF RHEUMATOID ARTHRITIS
           ACR Response Criteria
            ACR20 / ACR50 / ACR70

• 20% / 50% / 70% improvement in
– Swollen joint count
– Tender joint count
– Improvement in at least 3 of the following 5
  measures
 •   Patient’s global assessment of disease activity
 •   Physicians’ global assessment of disease activity
 •   Patient’s assessment of pain
 •   Acute-phase reactant (ESR, CRP)
 •   Disability (HAQ)  Felson DT et al. Arthritis Rheum. 1995;38:727–735.
                       Felson DT et al. Arthritis Rheum. 1998;41:1564–1570  .
              TREATMENT OF RHEUMATOID ARTHRITIS
             Disease Activity Score (DAS)
    Assessment of Improvement or Response
    – DAS = 0.54 • (RAI) + 0.065 • (sw) + 0.33•Ln(ESR) + 0.0072•GH

           • RAI = number of tender joints (t) calculated
             using
             Ritchie Articular Index
           • Number of swollen joints (sw)
           • Erythrocyte sedimentation rate (ESR,
             mm/hour)
           • General health status (GH) using a 100-mm
             visual analog scale (VAS)
High disease activity >3.7, low disease activity 2.4, remission <1.6
             TREATMENT OF RHEUMATOID ARTHRITIS
      Disease Activity Score 28 (DAS28)
      Assessment of Improvement or Response

•   DAS28 = 0.56 • (t28) + 0.28 • (sw28) + 0.70•Ln(ESR) + 0.014•GH


     –   Number of tender joints among 28 joints (t28)
     –   Number of swollen joints among 28 joints (sw28)
     –   Erythrocyte sedimentation rate (ESR, mm/hour)
     –   General health status (GH) using a 100-mm visual
         analog scale (VAS)

•   High disease activity >5.1, low disease activity <3.2, remission <2.6

                                    DAS28 = Simplified disease activity score.
    Simplified Disease Activity Index: SDAI

  SDAI =                                                     SDAI         Disease Activity
    Tender joint count (0-28)
  + Swollen joint count (0-28)
                                                                             Severe
  + Patient Global* (0-10 cm)
  + Physician Global*(0-10
     cm)                                                      40

  + CRP (mg/dL)                                                              Moderate

    Improvement:                                              20
    Major: > 20 points
                                                                             Low
    Minor: 10-20 points
    No:     < 10 points                                         5
                                                                             Remission
*Assessment of Disease Activity, based on VAS
Smolen JS, Breedveld FC, Emery P, et al. Rheumatology. 2003;42:244-257.
               Health Assessment
          Questionnaire – Disability Index

• 8 categories
• 20 questions
• Each ranges from 0 to 3
    – 0 = no difficulty, 1 = some difficulty, 2 = much difficulty
      or with assistance, 3 = unable
• Score 2 for item that uses devices &/or another
  person
• HAQ score is average of worst score in each of 8
  categories
• The total score ranges from 0 to 3
• MCID = .22
                             Buchbinder R et al. Arthritis Rheum. 1995;38:1568-1580.
                             Sullivan FM et al. Ann Rheum Dis. 1987;46:598-600.
     Health Assessment Questionnaire
                Categories
Dressing and Grooming
• Dress yourself, including shoelaces   Hygiene
   and buttons?                         • Wash and dry your body?
• Shampoo your hair?                    • Take a tub bath?
Arising                                 • Get on and off the toilet?
• Stand up from a straight chair?       Reach
• Get in and out of bed?                • Reach and get a 5-pound object
Eating                                     (e.g., a bag of sugar)?
• Cut your meat?                        • Bend down to pick up clothing
                                           from the floor?
• Lift a full cup or glass to
   your mouth?                          Grip
• Open a new milk carton?               • Open car doors?
Walking                                 • Open jars which have been
                                           previously opened?
• Walk outdoors on flat ground?
                                        • Turn faucets on and off?
• Climb up 5 steps?
                                        Activities
                                        • Run errands and shop?
                                        • Get in and out of a car?
                                        • Do chores such as
                                           vacuuming or yard work?
5-year Rheumatoid Arthritis Care Costs
             by HAQ
$45,000
$40,000
$35,000
$30,000
$25,000
$20,000
$15,000
$10,000
 $5,000
    $0
          0   0.5   1.0   1.5   2.0    2.5      3.0


                                  Fries Ann Rheum Dis 1999
   10-year Rheumatoid Arthritis Care
            Costs by HAQ
$80,000
$70,000
$60,000
$50,000
$40,000
$30,000
$20,000
$10,000
    $0
          0-0.6   0.6-1.3   1.3-1.8     1.8-3.0


                                      Yelin A&R 1999
             Short Form-36 Health
               Survey (SF-36)
• Validated, widely-used generic measure of HRQOL*
   – Eight domains
      • Scored 0-100
      • Age, sex-adjusted rates
   – Two summary scores
      • Physical component: PCS
         – Measures how decrements in physical function affect
           day-to-day activities
         – Impact of physical impairment/disability on HRQOL
      • Mental component: MCS
         – Impact of mental effect
         – Symptoms of pain on HRQOL
   – Normative-based scoring (mean: 50; SD: 10)                    Health-related quality of life
                                       Ware JE Jr, Sherbourne CD. Med Care. 1992;30:473-483
             Quality of Life
          Short-form 36 (SF-36)
• Satisfy minimum psychometric standards
  for generic health comparison
• Physical health: physical functioning, role-
  physical, bodily pain, general health
• Mental health: vitality, social functioning,
  role-emotional, mental health
• 5-10 minutes: self-administered, computer,
  telephone, or interviewer

       Ware Quality of Life & Pharmacoeconomics in Clinical Trials 1996
                    SF-36 Two-Component Model
                                               Physical
                                              component




 Physical       Role          Bodily       General                  Social     Role     Mental
                                                        Vitality
 function      physical        pain        health                  function   emotion   health




                                                Mental
                                              component

Ware JE Jr, Sherbourne CD. Med Care. 1992;30:473-483.
                          SF-36 Scores Worsen with
                            Comorbid Conditions
  Better
                                                                       Median
                     10
                      0
 Functioning Score
  SF-36 Physical




                     80


                     60


                     40


                     20


                     0
  Worse                        None                   One       Two or more
                             n=52 (38%)            n=32 (23%)    n=53 (39%)
                                      Number of Comorbid Conditions
Talamo J et al. Br J Rheumatol. 1997;36:463-469.
          Aggressive Therapy
            With DMARDs
• Monotherapy
  – Sequential monotherapy


• Combination Therapy
  – Continuous
  – Step-up
  – Step-down
      Monotherapy, If Aggressively Dosed

                              MTX 7.5 to 20 mg/wk Within 8 Weeks
                         80

                                                                       ACR20
                         60
          Patients (%)




                                                                       ACR50
                         40

                                                                       ACR70
                         20


                         0
                              0    2     4           6   8   10   12
                                              Months

Bathon JM et al. New Eng J Med. 2000;22:1586-1593.
                          Double and Triple Therapy

                     90
                          p < 0.05 p < 0.005                              MTX + HCQ
                     80
                                                                          MTX + HCQ + SSZ
                     70          78                                       MTX + SSZ
    Responders (%)




                           60                          p < 0.005
                     60                              55
                     50
                                      49
                                               40
                     40
                                                          29             26
                     30
                                                                                18
                     20                                            16
                     10
                     0
                                ACR20               ACR50               ACR70


HCQ = hydroxychloroquine; SSZ = sulfasalazine.
O’Dell JR et al. Arthritis Rheum. 2002;46:1164-1170.
          Step-Up therapy MTX & Leflunomide

 •    In the leflunomide and
      placebo groups, 46.2%                                       100
      and 19.5% of patients,                                                           Leflunomide
                                                                  90                   Placebo
      respectively, met ACR20
                                                                  80
      criteria at 24 weeks




                                             ACR20 Responders %
                                                                  70
      (P < 0.001)
                                                                  60
 •    The ACR20 responder                                         50
      rates (%) were                                              40
      consistently greater at                                     30
      each time point for the                                     20
      MTX and leflunomide                                         10
      group (solid line)                                           0
      compared with the MTX
                                                                        0   1   2     3     4   5    6
      and placebo group
                                                                                    Month
      (dotted line)

Kremer et al. Ann Int Med 2002;137:726-33.
                                           DMARD Retention Rates
                                           High-Dose vs Low-Dose MTX
                                 100                            High-dose Methotrexate (12.5mg/week)
                                                                Low-dose Methotrexate (10.0mg/week)
                                                                Sulfasalazine
     Cumulative Retention Rate




                                                                Chloroquine
                                  80


                                  60


                                  40


                                  20

                                  0
                                       0   12   24   36   48   60    72     84     96    108   120
                                                     Survival Time (months)
Log Rank Statistics:
P<0.001 for high-dose MTX > All other regimens; and for low-dose MTX > Other DMARDs
Aletaha D, Smolen JS. J Rheumatol 2002:29:1631-1638
             Erosions Occur Early in RA

    Time           % with Erosions Reference

    <3 months               26           Harrison et al. Arthritis
      Rheum; 2000.

    1 year (9 months) 62                Proudman. Arthritis Rheum;
      2000.
*   2 years           75                van der Heijde. Br J
      Rheumatol; 1995.

    2 years (4 months) 77               Boers et al. Lancet; 1997.

    2 years (9 months) 68               Peltomaa et al. J Rheum;
      2000.
    *At 2 years, 73% ± 5% of RA patients have erosions.
    Advances in the
Treatment of Rheumatoid
       Arthritis
ANTIGEN PRESENTATION
Antigen presentation

          T cell

                    T cell receptor

           a    b
    CD4
                                      Antigen



                    HLA class II molecule


  Antigen-presenting cell
            Breedveld FC, J Rheumatol 25(Suppl 53):3–7, 1998
ANTIGEN PRESENTATION AND
     CO-STIMULATION
The Role of TNF-a in RA Pathology
          Molecular Structure of Biologic Agents


Description                               Structure
Chimeric anti-TNF mAb


TNF-receptor p75 IgG1 construct

Fully human anti-TNF mAb

PEGylated humanized
anti-TNF Fab-fragment

TNF-receptor p55 PEG
  Human    Mouse    Synthetic element   Polyethylene glycol
               ACR Treatment Algorithm for RA
 Diagnosis and Initial Evaluation of RA
 • Establish Diagnosis of RA Early                     Initiate Therapy
 • Document Baseline Disease Activity and              • Patient Education
    Damage                                             • Start DMARD(s) Within 3 Months
 • Estimate Prognosis                                  • Consider NSAID
                                                       • Consider Local or Low-Dose Systemic
                                                          Steroids
                                                       • Physical Therapy/Occupational Therapy
      Periodically Assess Disease
      Activity/Progression
                                                                   Inadequate Response
                                                       (active disease after 3 months max therapy)

       Adequate Response to Therapy
                                                     Change/Add DMARDs

                   MTX Naïve                                 Sub-optimal MTX Response


   MTX                           Combo Rx          Combo         Other             Biologics
                   Other
                  Mono Rx                            Rx         Mono Rx


                                                                           Mono Rx       Combo Rx
Adapted from:. Arthritis Rheum. 2002;46:328-346.
GUIDELINES FOR MONITORING OF PATIENTS WITH RHUEMATOID ARTHRITIS ON METHOTREXATE, LEFLUNOMIDE OR BIOLOGICS (M05.*, M06.*, M08.*)

          ACUTE PRESENTATION AND UNTIL STABLE                                                  STABLE


BENEFIT          DESCRIPTION            NO PER YEAR             BENEFIT          DESCRIPTION              NO PER YEAR

SPECIALIST       CONSULTATION             MONTHLY               SPECIALIST       CONSULTATION                  3

GP               CONSULTATION                                   GP                                             3

PATHOLOGY        HAEMOGLOBIN              MONTHLY               PATHOLOGY        HAEMOGLOBIN                   3
                 WHITE CELL COUNT         MONTHLY                                WHITE CELL COUNT              3
                 PLATELETS                MONTHLY                                PLATELETS                     3
                 CREATININE                  4                                   CREATININE                    2
                 ALBUMIN                     1                                   ALBUMIN                       1

                 TOTAL PROTEIN               1                                   TOTAL PROTEIN                 1
                 AST                      MONTHLY                                AST                           3
                 ALT                      MONTHLY                                ALT                           3
                 GGT                      MONTHLY                                GGT                           3
                 RHEUMATOID FACTOR           1                                   RHEUMATOID FACTOR             1
                 CRP                      MONTHLY                                CRP                           3

RADIOLOGY        CHEST                          1               RADIOLOGY        CHEST                         1

                 HANDS, FEET OR                                                  HANDS, FEET OR
                 AFECTED JOINTS                 1                                AFECTED JOINTS         EVERY TWO YEARS

PHYSIOTHERAPY    CONSULTATION             MONTHLY               PHYSIOTHERAPY    CONSULTATION                  2

OT               CONSULTATION                   1               OT               CONSULTATION                  1
 Figure 71.15 Magnetic resonance imaging in RA. Coronal fat-suppressed gradient echo (three dimensional spoiled gradient echo) MR image of the wrist (TR/TE 56
ms/12 ms; flip angle, 30&#176;) shows multiple erosions in the scaphoid, triquetrum, trapezium and hamate bones (arrows). The articular cartilage appears abnormal at
                                                                the sites of subchondral bone erosion.



                                                                                                                 Downloaded from: Rheumatology (on 20 July 2005 11:26 PM)
                                                                                                                                                           © 2005 Elsevier
             Guidelines for the use of TNF blockers in Ank Spond

•   PATIENT SELECTION
                                                                       •   Patients with symptomatic enthesitis must have had an
•   Patients normally fulfilling modified New York criteria for            adequate therapeutic trial of at least two local steroid
    definitive AS                                                          injections unless contraindicated.
•   Radiological criteria                                              •   CONTRAINDICATIONS
•   ≥Grade 2, bilateral Sacroiliitis, or grade 2 to 4 unilateral       •   Pregnancy and breastfeeding, adequate contraception must be
    sacroiliitis                                                           practiced.
•   Clinical criteria                                                  •   Active infection
•   Low back pain and stiffness for 3 months, that improves with      •   Patients at high risk of infection, including:
    exercise but is not relieved by rest.
                                                                       •   Chronic leg ulcer
•   Limitation of motion of the lumbar spine in both sagittal and
    frontal planes.                                                    •   Previous Tuberculosis (See SARAA guidelines)
•   Limitation of chest expansion relative to normal values            •   Septic arthritis of a native joint within the past 12 months
    correlated for age and sex.                                        •   Sepsis of a prosthetic joint within the last 12 months or
•   ACTIVE DISEASE                                                         indefinitely if the prosthesis remains in-situ.
•   Active disease for 4 weeks                                        •   Persistent or recurrent chest infection.
•   BASDAI 4 (0-10) and an expert opinion that anti-TNF               •   Indwelling urinary catheter.
    treatment should be started.                                       •   History of Lupus or Multiple Sclerosis
•   TREATMENT FAILURE                             All patients must    •   Malignancy or premalignant states, excluding:
    have had an adequate therapeutic trial of at least 2 NSAIDs. A           –      Basal cell Carcinoma
    therapeutic trial is defined as:                                         –      Malignancy diagnosed and treated more than 10 years
•   Treatment for 3 months at maximal recommended doses or                         previously where the probability of total cure is very
    tolerated doses unless contra-indicated.                                        high).
•   Treatments for ≤3 months were treatment was withdrawn              •   Assessment of response
    because of intolerance, toxicity or contraindications.             •   BASDAI: 50% relative change or absolute change of 2 (scale
•   Patients with symptomatic peripheral arthritis (normally               0-10) and an expert opinion as to whether treatment is to
    having a lack of response to a local steroid injection for those       continue or not.
    with oligoarticular involvement) must have had a therapeutic       •   Evaluation should be made between six and twelve weeks.
    trial of NSAIDs, Sulphasalazine and Methotrexate, singly or in
    combination at adequate therapeutic doses. A therapeutic dose      •   (BASDAI may be obtained from www.spondylitis.org)
    of Sulphasalazine is considered to be at least 2grams daily and    •   Dosage Recommended dosage is 5mg/kg. Dose interval is
    for Methotrexate, at least 15mg/week. Intolerance to either or         recommended at 8 weeks. The initial dose may be followed by
    both of these agents should be considered a treatment failure.         two further loading doses at two weeks and at four weeks after
                                                                           initiation and thereafter continued at eight weekly intervals. A
                                                                           sub therapeutic response after six weeks should be considered
                                                                           a treatment failure.
             PATIENT RIGHTS

• What are they?
• Who watches?
• Who arbitrates?

• Section 15 of the ACT
  – If there is doubt, there is a legal process.
  – Are MA’s aware of the provisions?
                      GUIDELINES FOR THE USE OF TNF (TUMOUR NECROSIS FACTOR) BLOCKERS
Scientific evidence supports the use of these drugs in Rheumatoid Arthritis, Juvenile Rheumatoid Arthritis and Ankylosing
  Spondylitis, particularly where other therapies have failed. They should only be used by Rheumatologists or clinicians
experienced in the management of rheumatoid arthritis. The criteria for their use in Rheumatoid Arthritis are based on the
                      Working Party for the British Society of Rheumatology, published in April 2000)

                 A)     Patients must fulfil the 1987 ACR criteria for the diagnosis of Rheumatoid Arthritis

                          B)       Patients must have active disease as indicated by the following:
                                            1. Six or more swollen and tender joints
                                 2. Elevated ESR or CRP above the normal for that laboratory.
                    3. Signs of active disease should be present at two visits at least one month apart.
                   Failure or intolerance of Standard Disease Modifying Anti-rheumatic Drugs (DMARDs)

             1.Previous use of at least 3 DMARDs serially or in combination, one of which must be Methotrexate.
                         2. DMARDs should have been given a therapeutic trial of at least six months.
 3.DMARDS include Methotrexate, Chloroquine, Sulphasalazine, or Leflunomide. It must be noted that some patients may
 be intolerant of a drug. This should be regarded as a therapeutic failure. The dose of Methotrexate should be increased to
 25mg per week before being considered a failure unless the patient develops side effects. At doses above 15mg per week,
  consideration should be given to switching the route of administration to sub cutaneous injection. Consideration should
  be given to the use of combination Methotrexate and Leflunomide in patients refractory to the use of these agents alone.
   Caution must be exercised when using this combination due to the higher potential risk for toxicity. In deciding to use
                           Leflunomide due consideration must be given to its teratogenic potential.
NOTE: Infliximab should be infused at a supervised day facility with appropriately trained staff and resuscitation equipment
                                                               available.
                                                           Contraindications
                                                      Pregnancy / Breastfeeding
                                                             Infection risk
  Leg ulcers / TB / Septic arthritis within previous12 months / Native joint sepsis within 12 months / Prosthetic joint sepsis
                            indefinite if in-situ / Recurrent chest infection / indwelling urine catheter
                                                        Demyelinating disease
                                                  Malignancy / pre-malignancy state
                                                          Withdrawal Criteria
                                                              Malignancy
                                                       Significant drug toxicity
                                                               Pregnancy
                                                         Intercurrent infection

				
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