Transcript RHEUMATOID ARTHRITIS

RHEUMATOID
ARTHRITIS
Balqis Mohamad Zin (F0155)
15 th June 2012
What is Rheumatoid arthritis (RA)?
• It is an autoimmune disorder
• The deregulated immune system
starts to attack the joints
• Chronic systemic inflammatory
disorders Which the synovial (lines
and lubricates the joints) becomes
inflamed
• According to Arthritis Foundation
Malaysia, RA affects about 5
in
1000 people in Malaysia.
• Prevalence estimated to be
worldwide
1%
Pathophysiology
• Begins with inflammation
of the synovial lining.
• The
thin
membrane
proliferates, and become
transformed
into
the
synovial pannus.
• The pannus, a highly
erosive
enzyme-laden
inflammatory exudate 
invades articular cartilage,
 erodes bone  destroys
periarticular
structures
resulting
in
joint
deformities
Diagnosis
American Rheumatism Association Criteria (ACR)
Criteria
Definition
Morning stiffness
Morning stiffness in and around the joints at least 1 hour before maximal
improvement
Arthritis of three or more joints
areas
At least three joint areas simultaneously have soft tissue swelling or fluid
(not bony overgrowth alone) observed by a physician. The 14 possible
joints areas are (R/L):PIP, MCP, wrist, elbow, knee, ankle and MTP joints
Arthritis of hand joints
At least one joint area swollen as above in wrist, MCP or PIP joints
Symmetric arthritis
Simultaneous involvement of the same joint areas(as in 2) on both sides
of the body
Rheumatoid nodules
Subcutaneous nodules, over bony prominences, or extensor surfaces, or
in juxtaarticular regions, observed by a physician
Serum rheumatoid factor
Demonstartion of abnormal amounts of serum rheumatoid factor by any
method that has been positive in less than 5% of normal control subjects
Radiographic changes
Radiographical changes typical of RA on posteroanterior hand and wrist
x-rays, which must include erosions or unequivocal bony decalcification
localized to or most marked adjacent to the involved joint
Patient is said to have RA if she/he satisfied at least 4 of these 7 criteria
Aim
• To minimize joint damage
• to reduce joint swelling, stiffness and pain
• Improve quality of life
Pharmacological treatment
Pain Relief
Treatment
NSAIDs / COX2 inhibitors
DMARDs
Modification
of the disease
Biological
modifiers
NSAIDS/ COX-2 Inhibitors
• As adjunct therapy to DMARDs
• Primarily by inhibiting the prostaglandin synthesis.
• Reduce stiffness BUT do not slow disease progression or prevent
joint deformity
• Aspirin
• Celecoxib
• Diclofenac
• Indomethacin
• Meloxicam
• Naproxen
Corticosteroids
• Only given in a short period of time
• Helps to reduce the progression rate of disease
• Given not more than a year
• Low dosages of Oral corticosteroid
• 10mg of prednisolone or less
• Injected corticosteroid useful when flares involves only a few joints
• should not be given more than once every 3 months
Disease-Modifying Antirheumatic Drugs
(DMARDs)
• Initial therapy once patient diagnosed
• Should not be delayed beyond 3 months
• Proven to slow down RA activity
• May not be effective in up to 20% patients
Before DMARD treatment
After DMARD treatment
Methotrexate
MOA
MOA in treatment of RA is unknown but may affect immune
functions
Side effects
Arachnoiditis, reddening of skin, ulcerative stomatitis,
alopecia
Dose
Initial: 5-7.5mg / week, not exceed 20 mg/week
Special cautions
Hazardous agent – use appropriate precautions for handling
and disposal
•
•
•
Folic acid supplement (5mg/week) will be given as combination to reduce side effects .  MTX is
a folate antagonist
Should not be given on the same day as MTX is administered
• May reduce the effect of MTX
• Compete for dihydrofolate reductase enzyme
Folic acid should be taken on the next day after MTX is taken.
Hydrochloroquine
MOA
Impairs complement-dependant antigen-antibody reactions
Side effects
alopecia, angioedema, abdominal cramping, myopathy,
bronchospasm, nausea & vomiting
Dose
Initial: 310mg-465mg / day taken with food or milk. Dose may
increase to achieve optimum response. After 4-6 weeks, dose
should be reduced by ½ to a maintenance dose of 155-310mg/day
Special cautions
May cause opthalmic adverse effect/neomyopathy
Cyclosporin
MOA
Inhibition of production and release of interleukin-II and inhibits
interlukin II-induced activation of resting T-lymphocytes
Side effects
Hypertension, edema, hirsutism, nausea
Dose
Initial dose: 2.5mg/kg/day divided twice daily, may be increased
by 0.5-0.75 mg/kg/day: additional dosage increases may made
again at 12 weeks. Max: 4mg/kg/day
Special cautions
Monitor renal function closely. Use with cautions with other
potentially nephrotoxic drugs
Cost
RM 3.30 per tablet
Sulphasalazine
MOA
Act locally in the colon to decrease the inflammatory response
and systematically interferes with secretion by inhibiting
prostaglandin synthesis
Side effects
Headache, photosensitivity, anorexia, nausea, vomiting,
diarrhea
Dose
Initial: 0.5-1g/day; increase weekly to maintenance dose of
2g/day in 2 divided doses, max: 3 g/day
Special cautions
Use caution in patients with renal impairment, severe allergies
or asthma or G6PD deficiency: may cause folate deficiency(
supplement folate should be consider)
Penicillamine
MOA
Depresses circulating IgM rheumatoid factor, depresses T cell
but not B-cell activity
Side Effect
Common: nausea, anorexia, taste loss, blood disorders including
thrombocytopenia, aplastic anemia
Dose
Initially: 125-250mg daily before food for 1 month and increased
by similar amount at intervals of not less than 4 weeks to usual
maintenance of 500-750mg daily in divided doses.
Max: 1.5 g daily
Special Cautions
Toxicity may be dose related. Patient should be warned to
report promptly any symptoms suggesting toxicity (fever, sore
throat, chills, bleeding or bruising)
Azathioprine
MOA
Inhibit synthesis of DNA, RNA and proteins.
Side effects
fever, malaise, thrombocytopenia , nausea & vomiting
Dose
Initial: 1mg/kg/day given once daily or divided twice daily for 68 weeks; increase by 0.5mg/kg every 4 weeks until response or
up to 2.5mg/kg/day
Maintenance: reduce dose by 0.5mg/kg every 4 weeks until
lowest effective dose is reached
Special cautions
Has mutagenic potential to both men and women.
Hepatotoxicity may occur
Biological Modifiers
• Mimic the biological substances in human body
• Suppressed excessive macrophage- produced cytokines (TNF-α, IL-1,
IL-6, IL-8) which are abundant in rheumatoid synovial tissues and
fluids
Rituximab
MOA
A monoclonal antibody directed against the CD20 antigen on Blymphocytes. (imp. Role in development of RA)
Side Effects
Fever, chills, nausea, dizziness, weakness
Dose
as 2 infusions of 1000 mg with a 2-wk interval. Repeat according
to patient’s response
Special precautions
Hydrate patient well , Stabilise uric acid levels before treatment ,
Antihistamine should be given to prevent allergic reactions,
Painkiller and steroid to be given before each infusion
Cost
RM 5300/vial
Etanercept
MOA
Binds tumor necrosis factor(TNF) and blocks its interaction
with cell surface receptors
Side effects
Headache, abdominal pain, respiratory tract infection
Dose
50mg once a week
25mg twice a week (should separated by 72-96 hours)
Special cautions
Serious and potentially fatal infections have been reported
including bacterial sepsis and tuberculosis
Cost
RM 1000 per injection
Infliximab
MOA
Binds to TNF alpha, interfering with endogenous TNFα activity
Side effects
Headache, nausea, diarrhea, ALT increased (concomitant with
MTX), infections
Dose
In combination with MTX: 3mg/kg at 0, 2, and 6 weeks, then
every 8 weeks thereafter.
Special cautions
Opportunistic infections and/or reactivation of latent infections
have been associated with infliximab therapy
Cost
Rm 2250 per injection
Source: 2012 Update of the 2008 American College of Rheumatology Recommendations for the
Use of Disease-Modifying Antirheumatic Drugs and Biologic Agents in the Treatment of
Rheumatoid Arthritis
Source: 2012 Update of the 2008 American College of Rheumatology Recommendations for the
Use of Disease-Modifying Antirheumatic Drugs and Biologic Agents in the Treatment of
Rheumatoid Arthritis
Monitoring
• ESR/CRP
• LFT
• WBC
• Platelet
• Creatinine
Non-pharmacological treatment
• Occupational therapy
• Tai Chi
• Passive exercise should prescribed
Joint Protection Principles
Source:
http://www.afm.org.my/info/li
ving.htm
Treatment available in UMMC
Dose
Criteria
Methotrexate
5-7.5mg / week
Standard formulary.
Folic Acid
5mg OD
Standard formulary.
Prednisolone
5-10mg OD
Standard formulary.
Hydrochloroquine
155-310mg/day
Standard formulary
Cyclosporin
2.5mg/kg/day divided twice
daily
Restricted formulary.
Sulphasalazine
of 2g/day in 2 divided doses
Normal formulary.
Penicillamine
500-750mg daily
Normal formulary.
Rituximab
as 2 infusions of 1000 mg with
a 2-wk interval
Special formulary, to buy from Pharm
UMMC
Etenarcept
50mg once a week
Special formulary, to buy from Pharm
UMMC
Infliximab
3mg/kg at 0, 2, and 6 weeks,
then every 8 weeks thereafter.
Special formulary, to buy from Pharm
UMMC
Summary
• To minimize the pain and joint damage, proper treatment should be
given.
• Early treatment !!…. Reversible
• Counseling is important
• Side effect
• Administration
References
• BNF
• Drug information Handbook. 18 th Edition
• B.G.Wells, J.T. DiPiro,T.L Schwinghammer, C.V DiPiro. Pharmacotherapy
handbook, 7th edition, Mc Graw Hill
• M.A Koda-Kimble, L.Y Young, B.K.Alldredge, R.L Corelli, et al,. Applied
therapeutics, 9 th edition, Lippincott Williams & Wilkins
• J.A Singh, D.E Furst, et al. 2012 Update of the 2008 American College of
Rheumatology Recommendations for the Use of Disease-Modifying
Antirheumatic Drugs and Biologic Agents in the Treatment of Rheumatoid
Arthritis, Arthritis & Care Research, Vol 64 No.5 , May 2012.
• NICE guideline: The management of Rheumatoid Arthritis in adult, February
2009.
• “Stop it Before it Stops You”, by Dr Chow Sook Khuan, Consultant
Rheumatologist, Sunway Medical Centre , Keep Smiling, Volume 8/2008
• http://www.afm.org.my/info/ra.htm
• RHEUMATOID ARTHRITIS, National clinical guideline for management and
treatment in adults, Royal College of Physicians
• http://www.livestrong.com/article/420615-why-cant-i-take-folic-acid-the-sameday-as-methotrexate/