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

2. 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

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

4. 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: 4

5. 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

6. 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

7. DMARDs I: Major Nonbiologic DMARDs
Methotrexate
Sulfasalazine 7

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

9. 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

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

11. 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

12. 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

13. Etanercept
Drug interactions
Inactivates TNF 13

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

15. 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

16. 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

17. 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

18. 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

19. 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.

20. 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.

21. 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.