Rheumatoid Arthritis pathophysiology of RA stages of Arthritis diagnosis treatment

1. BY:
S. S. D. SREEJA
(M.Pharmacy I year)
G.Pullareddy College of Pharmacy
Under the guidance of:
Mrs. R. Padmavathy
Associate Professor (Ph.D)

2. • Rheumatoid Arthritis is a progressive, systemic and an Auto immune
disorder.
• The etiology is unknown.
• It is characterized by:
Symmetric synovitis – Chronic Polyarthritis.
Joint erosions, cartilage and bone destruction.
Multisystem - extra-articular manifestations.
Onset usually slow & insidious over months.
In 15 to 20% may have rapid or acute.
Aggressive management leads to good control.

3.  Prevalence of - 0.8% to 2.1% of the population
 Gender predilection ratio – Women: Men – 3:1
 Prevalence increases with age – Juvenile RA
 About 40-60% have severe disease – 3 fold  mortality
 Median life expectancy is shortened by 3 to 7 years
 Onset mostly between ages of 35 – 60 years

7.  Undifferentiated Polyarthritis
 Early RA – Mild Disease
 Severe RA with Deformities

8.  Wrist joints and MCP joints - very commonly involved
 Index and middle Metacarpophalangeal joints
 Proximal interphalangeal joints (PIP)
 Metacarpophalangeal joints (MCP)
 Metatarsophalangeal joints (MTP)
 Elbows, Shoulders
 Knees, Ankles, Hips. Lumbosacral area is not involved
 Spine: only Atlanto-axial joint (C1– C2), subluxation
 Terminal interphalangeal (TIPS) joints are not involved

9. Classification of RA Specification of activity levels
Class I Complete ability to perform daily activities
self-care, vocational and avocational
Class II Ability to perform usual self-care and vocational
activities; limited avocational activities
Class III Ability to perform usual self-care activities;
limited vocational or avocational activities
Class IV Limited ability to perform usual self-care or
vocational or avocational activities

12. Blood parameters :
• RA Factor (RA Factor is IgM Antibody to the Fc portion of the IgG)
• C – Reactive Protein (CRP)
• ESR
• Ceruloplasmin
• Haptoglobin
• Anti Nuclear Antibodies (ANA profile)
• Anti-CCP Antibody Test (antibodies to Cyclic Citrullinated Peptides)
ISOTOPIC Bone Scan

13.  Presence of > 20 inflamed joints
 Markedly elevated ESR
 Radiographic evidence of bone erosions
 Presence of rheumatoid nodules
 High titers of RA Factor and anti CCP
 Higher class of functional disability
 Persistent inflammation; comorbidities
 Advanced age of onset
 HLA-DR*0401 or DR*0404

14. 1. Relief of pain
2. Reduction of inflammation
3. Protection of articular structures
4. Maintenance of functional activity
5. Control of systemic involvement
6. Slow the progression of disease
7. Increase the over all quality of life

15.  Rest
 Exercise
 Flexibility/stretching
 Muscle conditioning
 Cardiovascular/aerobic
 Diet
 Weight management
 Physical and occupational therapy

17.  Gold complexes:
Sodium aurothiomalate
Auranofin
 Antimalarials:
Chloroquine
Hydrochloroquine sulfate
 Disease modifying Anti-Rheumatic Drugs (DMARDs):
Methotrexate
Azathioprine
Cyclosporin
Cyclophosphamide
Leflunamide

18.  NSAIDs:
Coxibs
Sulfasalazine
Naproxen
 Gluco Corticoids:
Prednisolone
Methyl Prednisolone
 Pencilline metabolites:
Pencillamine
 Biologicals:
TNF- alpha antagonists
IL-1 R antagonist

19.  Erosive changes occur early in disease
 Even a brief delay of therapy can have a significant impact on disease
parameters years later
 Early DMARD treatment to arrest progression
 MTX is the sheet anchor – Combination of DMARDs
 Bridge the gap initially with NSAID and GC
 Biologics only for refractory case – with caution; cost
 Surgical treatment options in selected patients

21.  The effect of sodium aurothiomalate and auranofin develops slowly
over 3-4 months.
 pain and joint swelling subsides and the progression of bone and joint
damage diminishes. The mechanism of action is not clear but inhibits
induction of IL-1 and TNF-alpha
 Side effects includes mouth ulcers, proteinuria, thrombocytopenia and
blood dyscriasis.

22.  Hydroxychloroquine and chloroquine are 4-amino quinolone drugs
 The antirheumatic effects do not appear until a month or more after
the drug is started.
 Side effects include dizziness, blurring of vision

23.  MTX is given 10 to 30 mg orally, IM, or SC per week
 It is DHF reductase inhibitor – Supplemental folic acid
 The clinical improvement takes one to two months
 Nausea, diarrhea; mouth ulcers; rash, alopecia; Abnormal LFT
 Rare: low WBC & platelets; pneumonitis; sepsis; liver disease; EBV related
lymphoma;
 CBC, creatinine, and LFTs monthly for six months, then every one to two
months; repeat AST or ALT in two to four weeks if initially elevated, and
adjust dose as needed;
 Rapid onset (six to 10 weeks); tends to produce more sustained results over
time than other DMARDs and lowers all-cause mortality;
 Can be used when cause of polyarthritis uncertain;
 Often combined with other DMARDs like Leflunomide, SSZ, HCQS

24. PROS
 Effective control of inflammation and pain
 Effective reduction in swelling
 Improves mobility, flexibility, range of motion
 Improve quality of life
 Relatively low-cost
CONS
 Does not affect disease progression
 GI toxicity common
 Renal complications (Irreversible renal insufficiency, papillary necrosis)
 Hepatic dysfunction
 CNS toxicity

25. PROS
 Anti-inflammatory and immunosuppressive effects
 Can be used to bridge gap between initiation of DMARD therapy
and onset of action
 Intra-articular steroid (IAS) injections can be used for individual joint
flares
CONS
 Does not conclusively affect disease progression
 Tapering and discontinuation of use often unsuccessful
 Low doses result in skin thinning, ecchymoses, and Cushingoid
appearance
 Significant cause of steroid-induced osteopenia

26. Etanercept Infliximab Adalimumab Anakinra Abatacept Rituximab
Target TNF TNF TNF IL-1
Receptor
T-Cell
Activation
B-Cell
Half Life 3-5 Days 8-10 Days 10-20 Days 4-6 Hrs 13-16 Days 19 Days
Construct Human Chimeric Human Human Human Chimeric
Dosing Once
Biweekly-
weekly
Once every
4-8 weeks
Once every 1-
2 weeks
Once
Daily
Once
Monthly
Twice every
6-12 months
Route Sub-Cut I.V. Sub-Cut Sub-Cut I.V. I.V.

27.  Active Hepatitis B Infection
 Multiple sclerosis, optic neuritis
 Active serious infections
 Chronic or recurrent infections
 Current neoplasia
 History of TB or evidence of Koch’s
 Congestive heart failure (Class III or IV)

28. THANK YOU