Drug Therapy of Rheumatoid Arthritis Chapter 73 Drug Therapy of Rheumatoid Arthritis 1

Drugs for Rheumatoid Arthritis Rheumatoid arthritis (RA) Autoimmune inflammatory disorder Treatment Relieve symptoms Maintain joint function Minimize systemic involvement Delay progression of disease Nondrug measures 2

Classes of Antiarthritic Drugs NSAIDs Nonsteroidal anti-inflammatory drugs DMARDs Disease-modifying antirheumatic drugs Nonbiologic DMARDs (traditional DMARDs) Biologic DMARDs Glucocorticoids Adrenal corticosteroids 3

Drug Selection for Rheumatoid Arthritis Protocol 2012 Update of the American College of Rheumatology Recommendations for the Use of Disease-Modifying Anti-Rheumatic Drugs and Biologics in the Treatment of Rheumatoid Arthritis is available at: www.rheumatology.org/practice/clinical/guidelines/Singh_ACR_RA_GL_May_2012_AC-R.pdf. 4

Drug Selection for Rheumatoid Arthritis Nonsteroidal anti-inflammatory drugs First-generation NSAIDs: Inhibit COX-1 and COX-2 Second-generation NSAIDs (coxibs): Selectively inhibit COX-2 (Celecoxib) Safety: All prescription-strength NSAIDs carry a boxed warning regarding risk of thrombotic events and gastrointestinal (GI) ulceration and bleeding  COX-1, Cyclooxygenase-1; COX-2, cyclooxygenase-2. 5

Drug Selection for Rheumatoid Arthritis Glucocorticoids Generalized symptoms: Oral glucocorticoids One or two joints are affected: Intra-articular injections Adverse effects Prednisone and prednisolone 6

DMARDs I: Major Nonbiologic DMARDs Methotrexate Sulfasalazine 7

Methotrexate Most rapid-acting DMARD Therapeutic effect: 3 to 6 weeks Adverse effects Hepatic fibrosis Bone marrow suppression GI ulceration Pneumonitis 8

Sulfasalazine Used to treat inflammatory bowel disease (IBD); now used for RA as well Anti-inflammatory and immunomodulatory actions Can slow progression of joint deterioration GI side effects may be intolerable 9

Other DMARDs I: Major Nonbiologic DMARDs Leflunomide [Arava] Hydroxychloroquine [Plaquenil] Minocycline [Minocin] Penicillamine Azathioprine [Imuran] Cyclosporine Prosorba column 10

DMARDs II: Major Biologic DMARDs Tumor necrosis factor (TNF) inhibitors Suppress immune function Pose risk of serious infection Work by neutralizing TNF Etanercept [Enbrel] Adalimumab [Humira] Certolizumab pegol [Cimzia] Golimumab [Simponi] Golimumab [Simponi Aria] Infliximab [Remicade] 11

Etanercept Action Use Adverse effects Inactivates TNF Moderate to severe RA Adverse effects Serious infections Severe allergic reactions Heart failure Hematologic disorders Liver injury Central nervous system (CNS) demyelinating disorders 12

Etanercept Drug interactions Inactivates TNF 13

Other Biologic DMARDs Infliximab [Remicade] Adalimumab [Humira] Golimumab [Simponi] Certolizumab pegol [Cimzia] 14

Other Biologic DMARDs Rituximab [Rituxan] Reduces the number of B lymphocytes Reduces symptoms of RA and slows disease progression Adverse effects: Infusion reactions, monocutaneous reactions, hepatitis B reactivation, progressive multifocal leukoencephalopathy (PML), others  15

Other Biologic DMARDs Abatacept [Orencia] First-in-class T-cell activation inhibitor Reduces symptoms of RA and disease progression Adverse effects: Headache, upper respiratory infection, nasopharyngitis, nausea, serious infections Vaccines  16

Other Biologic DMARDs Tocilizumab Interleukin-6 (IL-6) receptor antagonist Monoclonal antibody Action: Blocks receptors for IL-6, a proinflammatory cytokine that helps mediate the autoimmune attack against the joints of patients with RA Adverse effects: Serious infections, GI perforation, liver injury, neutropenia, thrombocytopenia 17

Other Biologic DMARDs Anakinra [Kineret] Blocks receptors for interleukin-1, a proinflammatory cytokine that plays a central role in synovial inflammation and joint destruction Risk of serious infection 18

Question 1 A patient with rheumatoid arthritis has been taking high-dose aspirin and complains of gastric upset and pain. What does the nurse anticipate will be prescribed for this patient? A. Taking a lower dose of aspirin B. Biweekly injections of methotrexate [Rheumatrex] C. Obtaining a prescription for celecoxib [Celebrex] D. Daily drug therapy with prednisone Answer: C Rationale: If aspirin causes gastrointestinal upset or pain, a cyclooxygenase-2 (COX-2) inhibitor (celecoxib) should be considered. Methotrexate is administered once a week. Daily prednisone therapy is not indicated; prednisone is usually administered for exacerbations and as short-term therapy.

Question 2 A patient with rheumatoid arthritis is prescribed methotrexate [Rheumatrex]. The nurse will expect to observe therapeutic effects with this drug in which time period? A. 3 to 7 days B. 3 to 6 weeks C. 3 to 4 months D. 1 to 2 years Answer: B Rationale: Methotrexate acts faster than all other disease-modifying antirheumatic drugs. Therapeutic effects may develop in 3 to 6 weeks.

Question 3 Which statement about enteracept does the nurse identify as true? The patient should stop taking the drug if redness appears at the injection site. Enteracept can cause liver injury. Live vaccines can be administered with enteracept. Enteracept is used to treat CNS demyelinating disorders. Answer: B Rationale: Tumor necrosis factor (TNF) inhibitors have been associated with severe liver injury, including acute liver failure. Injection-site reactions (redness, swelling, itching, pain) are common with these drugs. Inform patients that symptoms usually subside in a few days, and advise them to contact the prescriber if the reaction persists. TNF antagonists may increase the risk of acquiring or transmitting infection after immunization with a live vaccine. Accordingly, live vaccines should be avoided. Inform parents that pediatric vaccinations should be current before therapy with a TNF antagonist starts. TNF antagonists have been associated with rare cases of CNS demyelinating disorders, including multiple sclerosis, myelitis, and optic neuritis. Avoid TNF antagonists in patients with a preexisting or recent-onset demyelinating disorder.