Rheumatoid Arthritis

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Rheumatoid Arthritis
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BackgroundNICE T.A. No 72, NICE draft scope for
RA, Nov 2006ODell JR. N Eng J Med 2004 350
2591602

• RA is the most common inflammatory
  polyarthropathy in the UK
• Affects between 0.5 and 1 of the population
• Characterised by inflammation of the synovial
  tissue in joints, causing pain, swelling and
  stiffness and can lead to joint destruction
• Life expectancy reduced by 510 years compared
  with that of people without the condition, and
  3550 of this excess risk is accounted for by
  cardiovascular mortality
• Long-term prognosis for patients with RA depends
  not only on their joint disease but also on their
  co-existing illnesses

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Diagnosis of early RASIGN 2000

• Examination will usually show symmetrical
  swelling and tenderness of the small joints of
  the hands and feet (and to a variable extent the
  larger joints) and the presence of synovitis
  (i.e. soft tissue swelling in relation to the
  joint). Systemic 'flu-like' symptoms are not
  uncommon.
• Essential aspects of the consultation
• History
• Pain
• Stiffness after inactivity
• Joint swelling
• Fatigue
• Examination
• Affected joints
• Synovitis vs. bony swelling/deformity
• Range of movement
• Extra-articular features

4
Therapeutic approaches the old and the newLee
DM, et al. Lancet 2001 358 90311PRODIGY 2005
SIGN 2000 NPC New Medicines Overview 2002

• Pyramid approach
• No longer recommended
• Initial conservative management with NSAIDs for
  several years
• DMARDs were withheld until clear evidence of
  erosions was seen
• DMARDs then added individually in slow succession
  as the disease progressed
• Oral corticosteroids, cytotoxics (e.g.
  cyclophosphomide)
• Current approach
• Early referral for diagnosis
• Early treatment of diagnosed RA with DMARDs to
  control symptoms and delay disease progression

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Early referral for specialist assessmentPRODIGY
2004 Emery P, et al. Ann Rheum Dis 2002 61
2907

• Rheumatology referral is strongly recommended if
  symptoms persist for more than 6 weeks, even if
  there is a response to NSAIDs. Ideally, the
  person should be seen within 12 weeks of the
  onset of symptoms
• Early referral from primary care to a
  rheumatologist is recommended in the event of
  clinical suspicion of RA, which may be supported
  by the presence of any of the following
• Swelling of three or more joints
• Involvement of the metacarpophalangeal or
  metatarsophalangeal joints or
• Early morning stiffness of at least 30 min
  duration

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3 steps to NSAID HeavenNational Prescribing
Centre

• Dont use them unless you have to.
• If you have to use them, use them wisely.
• Use a safer drug (ibuprofen, then naproxen) in
  lowest effective dose for shortest period.
• NSAID users should be a high priority for
  medication reviews.
• Think about heart failure, hypertension and renal
  issues routinely.
• Consider gastroprotection in those at high risk
  (NICE definition).
• Options are misoprostol, PPIs, double dose H2RAs,
  and Cox-2s.
• Cox-2s are not a panacea and the balance of
  benefits and risks (GI, CV, skin, renal, etc.)
  needs to be carefully assessed.
• All of this particularly applies to those aged
  over 65

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Steroids and DMARDsBSR guidelines 2006 Emery P,
et al. Clinical Evidence 2003 SIGN 2000 ODell
JR, et al. Ann Intern Med 2007 146 45960

• Systemic steroid therapy beneficial in managing
  synovitis in early RA/flare or in bridging
  disease control between different DMARD therapies
  but long-term use is not justified
• Conflicting evidence for a disease-modifying
  effect
• Osteoporosis prevention should always be
  considered
• Sulphasalazine, and methotrexate (MTX) are the
  current DMARDs of choice due to their more
  favourable efficacy/toxicity profiles
• Leflunomide likely to be beneficial but can cause
  serious hepatic reactions and long-term safety is
  unclear
• Patients with RA should be established on DMARDs
  as soon as possible after RA is diagnosed
• But requires close monitoring under shared care
  arrangement
• Best to start with a single DMARD /- steroids
  and escalate through dose increases and
  combination therapy as required

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Biologic agents NICE TA 126 130 2007 BSR
guidelines April 2001 (updated 2005)

• Adalimumab, etanercept and infliximab are
  recommended as options for the treatment of
  adults who have both the following
  characteristics
• Active RA disease activity score (DAS28) gt 5.1
  on at least 2 occasions, one month apart
• Have undergone trials of two DMARDs, including
  MTX (unless contraindicated)
• TNF-alpha inhibitors should normally be used in
  combination with MTX. Where a patient is
  intolerant of MTX, or if MTX inappropriate,
  adalimumab and etanercept may be given as
  monotherapy
• Continue treatment only if adequate response
  (improvement in DAS28 1.2 points) at 6 months
• An alternative TNF-alpha inhibitor is recommended
  only where treatment is withdrawn due to ADRs
  before the initial 6 month assessment

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Biologic agents (cont) NICE TA 126 and 130 2007
BSR guidelines April 2001 (updated 2005)

• Escalation of doses above the licensed starting
  doses is not recommended
• Normally initiate treatment with least expensive
  drug
• Rituximab MTX is recommended as an option for
  the treatment of adults with severe active
  rheumatoid arthritis with inadequate response
  to/intolerance of other DMARDs, including at
  least TNF-alpha inhibitor
• All patients need to be screened and closely
  monitored for TBcontinue for 6 months after
  discontinuing infliximab