A proper description about Rheumatic arthritis. It containts DEFINITION, EPIDEMIOLOGY, ETIOLOGY, RISK FACTORS, PATHOPHYSILOGY, SIGN & SYMPTOMS, DIAGNOSIS, TREATMENT & DIFFERENCES BETWEEN RA & OA

1. TVM COLLEGE OF PHARMACY
BALLARI, KARNATAKA
PRESENTED BY :-
NIHARIKA NIHA, PHARM-D III Yr

2.  DEFINITION
 EPIDEMOLOGY
 AETIOLOGY
 RISK FACTORS
 DEFINITION
 PATHOPHYSILOGY
 SIGN & SYMPTOMS
 DIAGNOSIS
 TREATMENT

3.  Rheumatoid Arthritis(RA)
:- RA is a systemic autoimmune disease characterized by inflammatory
polyarthritis, which affects many joints, principally attacks synovial fluid.

4.  RA affects 0.5-1% of the population world-wide with a peak prevalence
between the age of 30 & 50 yrs.
 Women developing the condition three times more than men (3:1)
 40% of RA patients are registered as disabled within 3 yrs of onset & around
80% are moderately to severely disabled within 20 yrs.

5.  Gender :- Menopause women 3 time more than men.
-Female hormones may play a role in the disease
 Familial :- Having positive family history of RA
 Genetic factors :- Human leukocyte antigen(HLA)-DR4 & HLA-DRB1 which may
associated RA .
 Viruses or bacteria:- RA may be related to viruses or bacteria

6. RISK FACTORS
?SMOKING
OBESITY STRESSFAMILY HISTORY
AGING & HORMONAL
CHANGES
AVOID RISK FACTORS

10. Immune deficiency of T-Lymphocyte system which is triggered by some internal & external factors
Leads to uncontrolled synthesis of antibodies (IgG) by B-Lymphocytes
Plasmatic cells & lymphocytes of synovium percepts IgG as heterogeneous antigens & starts to produce rheumatic
factors against IgG
Immuno complex formation begins, this process stimulates different reactions, activation of complement system
which triggers immigration of polymorphonuclear leukocytes to the synovial fluid
Macrophages (Neutrophils) engulfs the immune complexes with further release of lysosomal enzymes and other
mediators of inflammation
This results to lesion of microcirculatory vessels and development of inflammatory changes in synovium
Continuous inflammation stimulates synovial membrane proliferation with formation of pannus, which is rambling on joint
cartilage. The outer lesion appear because of destruction of microcirculatory vessels of visceral organs by immune complexes

11.  Symmetrical polyarthralgia
 On set of pain
 Early-morning stiffness (lasting more than 30 minutes)
 Swelling in the small joints of the hands and feet
 Limit the joint movement
 Rheumatic noodles may also presented
NOTE:- Joint pain and stiffness of more than 6 weeks
duration.
 Systemic:- light Fever, Fatigue, Weight loss , Susceptibility
to infection
 Eyes:- Inflammation of eyes, Episcleritis, Scleritis,
Keratoconjunctivitis sicca
 Neurological :- Irritability, depression and carpal tunnel
syndrome
 Haematological:- Anaemia, Eosinophilia, thrombocytosis
 Lymphatic:- Lymphadenopathy, Felty’s syndrome,
Spleenomegaly
 Pulmonary:- Lung fibrosis, Pleural effusion , Rheumatoid
pneumoconiosis
 Heart & peripheral vessels:- Pericarditis , Pericardial
effusion, Myocarditis, Endocarditis, Coronary vasculitis
 Vasculitis:- Leg ulcers, Nail fold infracts, Gangrene of
fingers and toes
 Kidney:- Amyloidosis causes the nephrotic syndrome &
renal failure

12.  Rheumatoid factor (RF) detectable in 60% to 70%.
 Anticyclic citrullinated peptide (anti-CCP) antibodies have similar sensitivity to RF (50% to 85%) but are more
specific (90% to 95%) and are present earlier in the disease.
 Elevated ESR and C-reactive protein (CPR) are markers for inflammation.
 Usually a Normocytic normochromic anemia .
 Joint fluid aspiration may show increased WBC counts without infection, crystals.
 Periarticular osteoporosis, joint space narrowing or erosions.

13.  For 6 weeks or more
-Morning stiffness > 30 min
-Arthritis of three or more joints
-Arthritis of hand joints and wrists
 Symmetrical arthritis
 Subcutaneous nodules
 A positive serum rheumatic factor
 Typical radiological changes (erosions)

14.  Ruptured tendons
 Ruptured joints
 Joint infection
 Spinal cord compression
 Amyloidosis (rare)
 Heart disease
 Eye infection
 Side-effects of therapy

15.  A score of ≥6/10 is needed for classification of a patient as having definite RA
A. Joint involvement SCORE
 1 large joint 0
 2−10 large joints 1
1−3 small joints (with or without involvement of large joints) 2
 4−10 small joints (with or without involvement of large joints) 3
 >10 joints (at least 1 small joint)†† 5
B. Serology (at least 1 test result is needed for classification)
 Negative RF and negative ACPA 0
 Low-positive RF or low-positive ACPA 2
 High-positive RF or high-positive ACP 3
C. Acute-phase reactants (at least 1 test result is needed for classification)
 Normal CRP and normal ESR 0
 Abnormal CRP or normal ESR 1
D. Duration of symptom
 <6 weeks 0
 ≥6 weeks 1

16. GOAL OF
THERAPY

17.  Patient education
 Nutritional & dietary counseling
-Some study suggest that omega-3 fatty acid may
reduce rheumatoid arthritis inflammation
 Avoid precipitating factors like Smoking , Stress
 Rest :- It relieves stress on inflamed joints &
prevents of further joint destruction
 Occupational therapy :- It provide working
skills and techniques to patients.
 Physical therapies
-Splinting:- Prevents unwanted joints pain
-Exercise :- Which directed to muscle strength
& joint pain
 Weight reduction:- It used to reduce stress to
joints

19. Goals:-
 To reduce pain, swelling & morning stiffness by inhibiting COX
 Side effects should be minimize during use of drugs
 Chronic use should be minimized & Relatively low cost
Drugs
name
Dose Dosing Schedule Side effects Monitor
Aspirin Adult:- 300-600 mg
Child:-60-100 mg/
kg
4 times daily
(Aspirin rarely use now)
-Abdominal pain
-Ulcer, GI bleeding
-Blood in stool
-Dyspepsia,
-Nausea/Vomiting
- Rash ,Hepato-toxicity & CNS
depression
(Note):-Etoricoxib 90 mg od
has highest selectivity ratio for
inhibition of COX 2 & have
superior efficacy than
Naproxen 500mg bd over 12
-Ulcer
-GI bleeding
-Renal damage
Naproxen Adult:- 500 mg
Child:- 10mg/kg
2 times daily
( Effective)
Piroxicam Adult:- 10 – 20 mg 4 times daily
Diclofenac Adult:-150-200 mg 3-4 times daily
Ibuprofen Adult:-1.2-3.2 gm
Child:-20-40mg/kg
3-4 times daily
Celecoxib Adult:- 200–400 mg 2 times daily
Etoricoxib Adut:- 90 mg 1 time a day

20.  Second line agents
 Mostly used along with NSAIDS
 Pharmacological actions:-
 Anti-inflammatory & immunosupressent action
 Suppress signs & symptoms
 Slow appearance of new bone erosions
 Disadvantage:- 1) Tapering & discontinuation of use often unsuccessful
2) Low dose induced skin thinning & cushingoid appearance
Drugs Dose Dosage schedule Side effects Monitor
Prednisolone Initial dose :-
5-7.5 mg/day
Maintenance:-
5-60mg/day
1 or 2 times a day
(IV,IM,Oral,Topical)
Hypertension
hyperglycemia osteoporosis
Electrolyte imbalance
Delayed healing
Growth retardation
Bp, polyuria,
polydipsia, edema,
,visual changes,
weight gain,
headaches, broken
bone
•Intra-articular injections can be used for individual joint flares
•Reduce dose gradually

22.  Currently recommendation is to add DMARDs as soon as the diagnosis is
confirmed
 Slow acting , take 6 weeks to 6months to show the effects.
 Slow down disease progression
 Improve functional disability
 Decrease pain
 Interfere with inflammatory process
 Retard development of joint erosions

23.  All patients with Active disease
 May start from first day or even those patients who took NSAIDs for 3 months or more
 No strict gridlines to start DMARDs
 Methotrexate has rapid onset of action than other DMARD.
 Taking in account patient tolerance, cost considerations and ease of once weekly oral
administration METHOTREXATE is the DMARD of choice, most widely prescribed in the
world.
1)MTX + SSZ
2)MTX + Hydroxychloroquine
3)MTX + Lenflunomide
4)MTX + Lenflunomide

24. Drugs name Dose Side effect Monitoring Onset of action
Commonly used DMARDs
Methotrexate Initial dose:- 7.5 mg
Weekly 15-25 mg
Orally, S/C & I/M
GI upset,Hepatotoxicity
Bone marrow supression
Pulmonary fibrosis
Contraindicated in
pregancy
CBC, LFT 6-8 weeks
Chest X-ray annually
Urea & Cr. 3 monthly
Liver biopsy
1-2 months
Hydroxychloroqu
ine
Oral: 200–300 mg
bid
after 1–2 months
may
↓ to 200 mg bid or
daily
Skin pigmentation
Retinopathy, Cardiac
depression
Psychosis, Nausea, Abd.
pain
Fundoscopy
Opthalmoscopy 8-9
mnth
2-4 months
Sulfasalazine Oral: 500 mg bid,
then ↑ to 1 g bid max
myelosuppression, rash
photosensitivity, May
reduce sperm count,
nausea/vomiting
Blood count
LFT 6-8 weekly
1-2 months
Leflunomide 20 mg/day Nausea/vomiting, gastritis,
diarrhea, hair loss,
jaundice
Hepatitis
LFT 6-8 weekly 1-2 months

25. 1) The onset of action takes several months
2) There may be substantial toxicity which requires careful monitoring.
3) DMARDs have a tendency to lose effectiveness with time-(slip out).
 These drawbacks have made researchers look for alternative treatment strategies for RA-
The Biologic Response Modifiers.

26. Drugs name Usual dose/route Side effects Onset of action
Azathioprine 50-150 mg orally GI side effects
myelosuppression, Infection
1-2 months
Cyclosporin A 3-5 mg/kg/day Nephrotoxic , hypertension
Hyperkalemia
1-2 months
Cyclophosphamide 50 -150 mg orally Myelosuppression
Gonadal toxicity ,
Hemorrhagic cystitis , Bladder cancer
1 momths
.
.

27.  Newer drugs that reduce RA inflammation in a more highly targeted manner than
DMRDs.
 These are used in inadequate response of DMARDs
 These used to target very specific proteins responsible for inflammatory prcess.
 It also used to reduce progression of joint damage
1) TNF alpha inhibitors : Infliximab ,Etanercept & Adalimumab
2) IL-1 receptor antagonist : Anakinra
3) IL-6 receptor antagonist : Tocilizumab
4) Anti CD20 antibody : Rituximab
5) T-cell costimulatory inhibitor : Abatacept

28. Agent Usual dose/route Side effects Contraindication
Infliximab
(Anti-TNF)
T1/2:- 9 day
-3 mg/kg i.v infusion at wks 0,2
and 6 weeks then q 8 weeks
-Has to be combined with MTX.
Infusion reaction
URTI, Nausea
Activation of latent TB
Active infections, uncontrolled DM,
surgery(with hold for 2 wks post
op)
Etanercept
(Anti-TNF)
.
T1/2:- 4 days
-25 mg s/c twice a week or 50 mg
SC weekly
-May be given with MTX or as
monotherapy
Injection site reaction,
Opportunistic infection
Activation of latent TB
Active infections, uncontrolled DM,
surgery(with hold for 2 wks post
op)
Adalimumab
(Anti-TNF)
T1/2:- 2 weeks
-40 mg s/c every 2 wks
-May be given with MTX or as
monotherapy
Same as that of infliximab Active infections
MOA:-
1) Infliximab :- It is IgG1 monoclonal antibody that binds with TNF alpha & suppress inflammation process
2) Etanercept:- It is recombinant protein consisting of two soluble TNF p75 receptor moieties, which linked to Fc
portion of human IgG. It binds TNF alpha molecules and inhibit binding Cell surface. Thus decrease new erosion.
3)Adalimumab:- It is fully human IgG1 TNF monoclonal antibody complexes with soluble TNF alpha & prevents its
interaction with cell surface receptors causing down regulation of macrophages and T-cell function

29. Drugs name Dose Side effects Contraindication
Anakinra
(Anti-IL-1)
100 mg SC daily Injection site pain
Infections
Neutropenia
Active infections
Abatacept
(CTLA-4-IgG1 Fusion protien)
Co-stimulation inhibitor
<60 kg – 500 mg
60-100 kg- 750 mg
>100kg-1000mg
Infections
Infusion reactions
Active infection TB
Concomittant with other
anti-TNF-α
Rituximab
(Anti CD20)
1000 mg iv at
0, 2, 24 wks
Infusion reactions
Infections
Same as above
Tocilizumab
( Anti IL-6)
4-8 mg/kg
8 mg/kg iv monthly
Infections, infusion
reactions,dyslipidemia
Active infections

30.  They vary according to grade of injury
 In a flexible foot with an inflamed tendon stripping cleaning (tenosynovectomy)
 In case of rupture - (tendon transfer)
 In a more rigid foot - (Osteotomy)
 Joints replacement
 All these procedures have long time up to 1year .