Rheumatoid arthritis - Pharmacotherapy

1. Rheumatoid Arthritis
Areej Abu Hanieh
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2. Background
 Rheumatoid arthritis (RA) is a chronic,
progressive inflammatory disorder of
unknown etiology characterized by
polyarticular symmetric joint involvement
and systemic manifestations.
 The disease is three times more common
in women.
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3. Pathophysiology
 RA results from dysregulation of humoral and cell-
mediated immunity.
 Most patients produce antibodies called rheumatoid
factors.
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5. Clinical presentation
 Symptoms:
 Joint pain and stiffness of more than 6 weeks’ duration.
 Fatigue, weakness, low-grade fever, loss of appetite.
 Signs:
 Tenderness with warmth and swelling over affected joints.
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6.  Laboratory tests:
 Rheumatoid factor (RF) detectable in 60% to 70%.
 Anticyclic citrullinated peptide (anti-CCP) antibodies.
 Elevated ESR and CRP.
 Normocytic normochromic anemia.
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7. Joint involvement
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8. EXTRA-ARTICULAR INVOLVEMENT
 Rheumatoid Nodules
 Vasculitis
 Pulmonary Complications
 Ocular Manifestations
 Cardiac Involvement
 Felty Syndrome
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9. Treatment
 Goals:
 The primary objective in the treatment of RA is to achieve remission or low disease
activity which is referred to as “Treat to Target.”
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10. NONPHARMACOLOGIC THERAPY
 Rest.
 Occupational and physical therapy.
 Use of assistive devices.
 Weight reduction.
 Surgery.
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11. Pharmacologic Therapy
 Conventional synthetic DMARDs.
 Biologic DMARDs (referred to as biologics).
 NSAIDs , corticosteroids.
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12.  DMARDs:
methotrexate, hydroxychloroquine, sulfasalazine,
and leflunomide.
 Biologic DMARDs :
 TNFi drugs: adalimumab,
certolizaumab, etanercept, golimumab , infliximab.
 Non – TNFi : abatacept, tocilizumab, and rituximab,
 Tofacitinib
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13.  Agents less frequently used because of reduced efficacy and/or greater
toxicity: anakinra, azathioprine, d-penicillamine, minocycline, cyclosporine,
and cyclophosphamide.
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14.  DMARD monotherapy, preferably with methotrexate, is first-line therapy.
 Monotherapy with nonmethotrexate DMARDs or combination therapy with two or
more DMARDs may be effective when the initial DMARD treatment is
unsuccessful.
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15.  DMARD combinations:
 methotrexate plus hydroxychloroquine.
 methotrexate plus leflunomide.
 methotrexate plus sulfasalazine.
 sulfasalazine, hydroxychloroquine, and methotrexate.
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16.  The biologic agents have proven effective for patients who fail treatment with
DMARDs.
 Therapy with DMARDs and biologics result in immunosuppression
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18. Methotrexate
 DMARD of choice for initial therapy of most patients with RA. It
inhibits cytokine production, inhibits purine biosynthesis.
 The toxicities of methotrexate therapy are mainly gastrointestinal,
hematologic, pulmonary, and hepatic.
 Methotrexate can induce a folic acid deficiency.
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19.  Methotrexate is contraindicated in pregnant and nursing women
as it is teratogenic.
 It is also contraindicated in patients with chronic liver disease,
immunodeficiency, pleural or peritoneal effusions, leukopenia,
thrombocytopenia, preexisting blood disorders, and a creatinine
clearance of less than 40 mL/min (0.67 mL/s).
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20. Leflunomide
 It inhibits pyrimidine synthesis, leading to a decrease in
lymphocyte proliferation and modulation of inflammation.
 The drug may cause liver toxicity and is contraindicated in
patients with preexisting liver disease.
 Teratogenic.
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21. Hydroxychloroquine
 Often used in mild RA or as an adjuvant in combination DMARD
therapy in more progressive disease.
 The main advantage of hydroxychloroquine is the lack of
myelosuppressive, hepatic, and renal toxicities that may be seen with
other DMARDs, which simplifies monitoring.
 Onset may be delayed for up to 6 weeks.
 Cause retinal toxicity, should do ophthalmic examination
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22. Sulfasalazine
 Prodrug, is cleaved by bacteria in the colon into sulfapyridine and
5-aminosalicylic acid.
 Antirheumatic effects should be seen in 2 months.
 Gastrointestinal adverse effects such as nausea, vomiting,
diarrhea, and anorexia are the most common.
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23. Tofacitinib
 JAK inhibitor for use in patients with moderate to severe RA who
have failed, or have intolerance to methotrexate.
 Tofacitinib should not be given with biologics.
 Initiation of tofacitinib should be avoided in patients with severe
hepatic impairment, lymphocyte count less than 500 cells/mm3 ,
or hemoglobin less than 9 g/dL.
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24. Biologic agents
 Biologic agents are genetically engineered protein
molecules that block the proinflammatory cytokines .
 These agents have no toxicities requiring laboratory
monitoring, but they do carry a small increased risk for
infection
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25. TNF-α Inhibitors
 ETANERCEPT:
 It binds to and inactivates TNF.
 Given by subcutaneous injection.
 Aside from local injection-site reactions, adverse
effects are rare.
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26.  INFLIXIMAB
 Chimeric antibody combining portions of mouse and human IgG1.
 Oral methotrexate should be given concurrently in doses typically used
treat RA for as long as the patient continues on infliximab.
 An acute infusion reaction with fever, chills, pruritus, and rash may occur
within 1 to 2 hours after administration.
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27.  ADALIMUMAB
 human IgG1 antibody to TNF.
 Because it has no foreign protein components, it is less antigenic
than infliximab.
 GOLIMUMAB
 CERTOLIZUMAB
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28. Non-TNF Biologics
 ABATACEPT
 Inhibits interactions between the antigen-presenting cells and T cells.
 The drug is given by IV infusion based on patient weight.
 May be used as monotherapy or in combination with DMARDs.
 The adverse effects include headache, nasopharyngitis, dizziness, cough,
back pain, hypertension, dyspepsia, urinary tract infection, rash, and
extremity pain
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29.  RITUXIMAB
 Monoclonal chimeric antibody.
 Useful in patients who failed MTX or TNF inhibitors.
 Methylprednisolone100 mg should be given 30 minutes prior to rituximab.
 and antihistamines may also be of benefit in patients who have a history of
reactions.
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30.  TOCILIZUMAB
 humanized monoclonal antibody that attaches to IL-6
receptors.
 It is used as either monotherapy or in combination
with methotrexate or another DMARD.
 The rates of adverse events are generally low.
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