Rheumatoid arthritis (RA) is a chronic, progressive inflammatory disorder of unknown etiology characterized by polyarticular symmetric joint involvement and systemic manifestations.

1. PRESENTED BY:
Dr.SHAISTA SUMAYYA
PHARMD
SULTAN UL ULOOM COLLEGE OF PHARMACY, HYDERABAD

2. DEFINITION
 Rheumatoid arthritis (RA) is a chronic, progressive inflammatory disorder
of unknown etiology characterized by polyarticular symmetric joint
involvement and systemic manifestations.

3. PATHOPHYSIOLOGY

6. CLINICAL PRESENTATION:
 EARLY FEATURE:
 Most commonly affects MCPJ and PIPJ, wrist, tendon sheaths around the
joints (wrist – feet – knee – shoulder )
 Bilateral symmetrical polysynovitis
 Pain, fusiform swelling, stiffness, loss of mobility
 Constitutional symptom:
- malaise, low-grade fever
- tenosynovitis

7.  LATE FEATURE (DESTRUCTIVE)
 Spread to other joint
 Morning stiffness(more than 30mins) – improve with activity
 MORE LATER (DEFORMITY)
 Pain, deformity, instability, decreased ROM
 Thumb – Z-deformity
 Fingers – swan neck deformity, boutonniere’s deformities, ulnar deviation
 Wrist – radial and volar displacement
 Elbow – limited extension
 Shoulder – limited abduction
 Knees – swollen
 Toes – clawed

9. RISK FACTORS
 Factors that may increase your risk of rheumatoid arthritis include:
 Gender . Women are more likely than men to develop rheumatoid arthritis.
 Age. Rheumatoid arthritis can occur at any age, but it most commonly begins in middle
age.
 Family history. If a member of your family has rheumatoid arthritis, you may have an
increased risk of the disease.
 Smoking. Cigarette smoking increases your risk of developing rheumatoid arthritis,
particularly if you have a genetic predisposition for developing the disease. Smoking
also appears to be associated with greater disease severity.
 Environmental exposures. Although poorly understood, some exposures such as
asbestos or silica may increase the risk of developing rheumatoid arthritis.
 Obesity. People — especially women age 55 and younger — who are overweight or
obese appear to be at a higher risk of developing rheumatoid arthritis.

10. EULAR RA CLASSIFICATION CRITERIA

11. DIAGNOSIS
Laboratory tests
 Rheumatoid factor (RF) detectable in
60% to 70%.
 Anticyclic citrullinated peptide (anti-
CCP) antibodies have similar sensitivity
to RF but are more specific and are
present earlier in the disease.
 Elevated erythrocyte sedimentation rate
and C-reactive protein are markers for
inflammation.
 Normocytic normochromic anaemia is
common as is thrombocytosis.
Other diagnostic tests
 Joint fluid aspiration may show
increased white blood cell counts
without infection, crystals.
 Joint radiographs may show
periarticular osteoporosis, joint space
narrowing, or erosions.

12. RADIOGRAPHIC EXAMINATION

13. TREATMENT
 NON PHARMACOLOGICAL:
 Diet
 Exercise
 Stress reduction
 Emotional support
 SURGERY:
 Synovectomy
 Arthroscopic surgery
 Osteotomy
 Arthroplasty
 Arthrodesis

14. PHARMACOLOGIC THERAPY

15. MEDICATIONS

17. ALGORITHM FOR TREATMENT OF RA

18. Management:
 Before start of therapy:
 CBC
 Serum creatinine – should be normal
 LFT – SGOT, SGPT should be normal
 Viral markers
 Chest x ray – ask history of TB
 Rheumatoid factor
 ESR/CRP
 After start of therapy:
 Monitor CBC, serum creatinine, LFT, ESR every 3 months

19. DMARDS
 should be started within the first 3 months of symptom onset
 DMARDs commonly used include methotrexate, hydroxychloroquine,
sulfasalazine, and leflunomide.
 Methotrexate is first line agent

20. DRUG OF CHOICE FOR RA
 METHOTREXATE
 DOSE: 7.5mg/week – 25mg/week
 Start with 10mg/week
 MTX shows response after 6-12 weeks
 Patient needs to report after 2-4 weeks with LFT
 If patient has tolerated the dose then increase dose @5mg/week up to 25mg/week
 FORM OF THERAPY:
 Below 15mg/wk. – oral
 Above 15mg/wk. – SC/IM
 Intrathecal for single joint involvement – usually given in cancer
 HOW LONG TO GIVE THE THERAPY?
 3-5 yrs. minimum duration of therapy
 Patients with response to MTX cures with more frequency

21.  MOA:
 Methotrexate inhibits cytokine production, inhibits purine biosynthesis,
and may stimulate release of adenosine, all of which may lead to its anti
inflammatory properties.
 ADR OF MTX: GI (stomatitis, nausea/vomiting, diarrhoea),
myelosuppression (thrombocytopenia, leukopenia), hepatic (elevated
enzymes, rarely cirrhosis), pulmonary (fibrosis, pneumonitis), rash
 Contraindications:
 chronic liver disease
 Immunodeficiency
 pleural or peritoneal effusions
 leukopenia, thrombocytopenia, preexisting blood disorders
 creatinine clearance of less than 40 mL/min.

22. LEFLUNOMIDE
 Used as Alternative to MTX
 Leflunomide is a DMARD that inhibits pyrimidine synthesis, leading to a decrease in
lymphocyte proliferation and modulation of inflammation.
 Leflunomide has efficacy similar to methotrexate for treating rheumatoid arthritis.
 DOSE: loading dose – 100mg daily for 3 days
 maintenance dose – 20mg daily
 Lower doses - if patients have gastrointestinal intolerance, complain of hair loss, or have
other signs of dose-related toxicity.
 contraindicated in patients with preexisting liver disease.
 The drug is teratogenic,
 Because leflunomide undergoes enterohepatic circulation, the drug takes many months to
drop to a plasma concentration considered safe during pregnancy. Hence should be given to
patients who are above 40yrs.
 Cholestyramine may be used to rapidly clear the drug from plasma

23. HYDROXYCHLOROQUINE
 The main advantage of hydroxychloroquine is the lack of
myelosuppressive, hepatic, and renal toxicities that may be seen with other
DMARDs, which simplifies monitoring
 Dose: Oral: 200–300 mg bid, after 1–2 months may ↓ to 200 mg bid or
daily
 OTHER DMARDS:
 Sulfasalazine, Gold salts, azathioprine, D-penicillamine, cyclosporine,
cyclophosphamide, and minocycline have all been used to treat
rheumatoid arthritis.

24. BIOLOGICAL DMARDS - BIOLOGICS
 Effective for patients who fail treatment with other DMARDs.

25. IMPORTANT POINTS REGARDING
BIOLOGICS
 Given when response to DMARD’s
alone is poor
 Biologics always given in combination
with MTX in RA
 Increase the risk of infections
 Screen for latent TB and hepatitis B
before therapy
 There should be no infections before,
while or after starting the therapy
 Patient should be asked to report
slightest infection
 Vaccinate for influenza
 If patient already has an infection, treat
the infection before starting therapy
 Tuberculin skin testing is recommended
prior to treatment with these drugs.
 If patient develop infections while on
biologic agents temporarily discontinue
them until the infection is cured.
 Given for a short course of 3-9 months
 High cost

26. INFLIXIMAB
 DOSE: IV infusion of 3 mg/kg at 0, 2, and 6 weeks and then every 8 weeks.
 Infliximab should be given in combination with methotrexate to prevent
development of antibodies that may reduce drug efficacy or induce
allergic reactions.
 combination of methotrexate plus infliximab halted progression of joint
damage in patients and was superior to methotrexate monotherapy

27. CORTICOSTEROIDS
 They are valuable in controlling symptoms before the onset of action of
DMARDs.
 This is referred to as a “bridge therapy”
 A burst of corticosteroids can be used in acute flares.
 Continuous low doses may be adjuncts when DMARDs do not provide
adequate disease control.
 may be injected into joints and soft tissues to control local inflammation
 Prednisone is the most often used steroid in RA treatment.
 ADR: Hypertension, hyperglycaemia, osteoporosis

28. USE OF STEROIDS IN RA
 Lowest dose – prednisone ≤ 7.5mg/day
 Lowest duration - ≤ 3 months
 Used as initial therapy with MTX
 INTRAMUSCULAR ROUTE: preferred in patients with compliance problems.
 Ex: triamcinolone acetonide, triamcinolone hexacetonide, and methylprednisolone
acetate.
 provides the patient with 2 to 6 weeks of symptomatic control.
 INTRAARTICULAR STEROIDS: preferred due to lesser side effects
 Given if small number of joints are affected
 one joint should not be injected more than 2-3 times /year because of the risk of
accelerated joint destruction and atrophy of tendons..
 Daily supplements of calcium (800–1,000 mg) and vitamin D (400–800 units) are
recommended along with steroids.

29. NSAIDS
 Adjuncts to DMARD treatment.
 Reduce stiffness and pain associated with rheumatoid arthritis.
 Few examples of NSAIDS:
 Aspirin 2.6–5.2 g ---Four times daily
 Celecoxib 200–400 mg — Daily to twice daily
 Diclofenac 150–200 mg — Three times per day to four times daily
 ADR: GI ulceration and bleeding, renal damage
 Aspirin - contraindicated in children

30. COMBINATION THERAPY
 Given when there is active disease even when MTX is ≥15mg/wk. for 8-12
weeks
 TRIPLE THERAPY:
 MTX+ sulfasalazine(1-2g/day)- start with 500mg/day +
hydroxychloroquine(200-400mg/day)
 Given to patients who didn’t respond to MTX alone
 OR
 Leflunomide (100mg daily for 3 days then 10-20mg daily)+ sulfasalazine +
hydroxychloroquine
 Methotrexate + sulfasalazine +prednisone
 infliximab + methotrexate

31. JUVENILE IDIOPATHIC ARTHRITIS
 Clinical presentation:
 The morning stiffness and joint pain may manifest as increased irritability, guarding of involved
joints, or refusal to walk. Fatigue, low-grade fever, anorexia, weight loss, failure to grow
 Treatment:
 NSAID:
 NSAID therapy is the treatment of choice for treating the joint manifestations as well as the febrile
episodes in systemic-onset JIA
 Ex: Naproxen 10 to 15 mg/kg/day (maximum, 750 mg) in two daily divided doses
 DMARD:
 For patients with polyarticular disease MTX is given 5 to 15 mg/m2 (0.15–0.5 mg/kg) orally or
subcutaneously each week
 BIOLOGIC DMARD:
 Etanercept (Enbrel), the only FDA-approved biological agent for the treatment of JIA
 Indicated for patients 4 years of age and older whose conditions have failed to respond to one or
more DMARDs
 Dose : 0.4 mg/kg (maximum, 25 mg) subcutaneously twice weekly.

32. ANEMIA IN RA
 RA can cause anemia of chronic disease
 If MTX is given, give folic acid to manage anemia
 If MTX is causing Hb drop >1-2g/dl – discontinue MTX
 HEPATITIS IN RA:
 Hydroxychloroquine+ sulfasalazine
 Do not give biologics
 RENAL DYSFUNCTION:
 If sr. creatinine is >30ml/min low dose MTX is given
 If sr. creatinine is <30ml/min, sulfasalazine+ low dose hydroxychloroquine

33.  HIV+ RA:
 Antiviral drugs+low dose hydroxychloroquine+sulfasalazine/low dose MTX
 Avoid biologics

34. VITAMIN SUPPLEMENTS
 Folic acid - Because MTX is a folic acid antagonist, it can induce a folic acid
deficiency. This deficiency is thought to be partly responsible for methotrexate
toxicity, and supplementation with folic acid does alleviate some adverse effects.
Dose: 5mg weekly/5mg daily other than the day of MTX administration
 Vitamin D- given as weekly therapy for 8-10 weeks, then given as monthly therapy
 Calcium- initially 1g/day, later 500mg/day
 Vitamin B12

35. MANAGEMENT OF RA DURING
PREGNANCY
 BEFORE PREGNANCY:
 Discontinue MTX at least 3 months before pregnancy - teratogenic
 If pregnancy is confirmed – discontinue MTX
 Controlled disease for at least 6 months
 Avoid MTX, leflunomide and biologics during pregnancy
 DURING PREGNANCY:
 1st trimester – hydroxychloroquine ±sulfasalazine
 2nd trimester – hydroxychloroquine + sulfasalazine
 3rd trimester – hydroxychloroquine + steroids SOS
 POST DELIVERY:
 Hydroxychloroquine

36. COMPLICATIONS OF RA
 Rheumatoid arthritis increases your risk of developing:
 Osteoporosis. Rheumatoid arthritis itself, along with some medications used for treating
rheumatoid arthritis, can increase your risk of osteoporosis — a condition that weakens your
bones and makes them more prone to fracture.
 Rheumatoid nodules. These firm bumps of tissue most commonly form around pressure points,
such as the elbows. However, these nodules can form anywhere in the body, including the lungs.
 Sjogren's syndrome People who have rheumatoid arthritis are much more likely to experience
Sjogren's syndrome, a disorder that decreases the amount of moisture in your eyes and mouth.
 Felty’s Syndrome: Rheumatoid arthritis in association with splenomegaly and neutropenia is
known as Felty’s syndrome. Thrombocytopenia also may be a manifestation of the syndrome
 Abnormal body composition. The proportion of fat to lean mass is often higher in people who
have rheumatoid arthritis, even in people who have a normal body mass index (BMI)..

37.  Carpal tunnel syndrome. If rheumatoid arthritis affects your wrists, the
inflammation can compress the nerve that serves most of your hand and
fingers.
 Heart problems. Rheumatoid arthritis can increase your risk of hardened
and blocked arteries, as well as inflammation of the sac that encloses your
heart(pericarditis)
 Lung disease. People with rheumatoid arthritis have an increased risk of
inflammation and scarring of the lung tissues, which can lead to
progressive shortness of breath.
 Lymphoma. Rheumatoid arthritis increases the risk of lymphoma, a group
of blood cancers that develop in the lymph system

38. How to differentiate between RA and
Ankylosing spondylitis
Rheumatoid arthritis
 Most common in females (35-50yrs)
 Pain in knuckles, hands, small joints –
deformity occurs if therapy is not
given
 CSR, CRP elevated
 Positive rheumatoid factor
 Positive anti citrullinated antibody
Ankylosing spondylitis
 Young males(20-40yrs)
 Patient complaints of backache in the
morning
 Sacro- ileac joint inflammation
 Buttock pain
 Bamboo spine
 Pain at rest – goes away on exercising
 HLA B27 positive

39. OSTEOARTHRITIS AND RA

40. THANK YOU