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Content Update

May 19, 2021

FDA Issues Another Safety Alert for the Janus-Kinase Inhibitor Tofacitinib (Xeljanz): Initial results of a postmarketing safety trial found that tofacitinib 5 mg or 10 mg twice daily was associated with higher incidence of serious CV events and cancer compared to patients treated with a TNF inhibitor (adalimumab or etanercept). FDA is awaiting additional results regarding risk for pulmonary emboli and death. Until the complete study results are available, clinicians should consider the potential risks and benefits of prescribing or continuing tofacitinib for its approved indications of rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis.

Content Update

August 19, 2019

Upadacitinib (Rinvoq) Approved for Treatment of Rheumatoid Arthritis: In August 2019, the U.S. Food and Drug Administration approved upadacitinib as the third oral janus kinase (JAK) inhibitor for treatment of rheumatoid arthritis. Upadacitinib 15 mg orally once daily is indicated for adults with moderately-to-severely active rheumatoid arthritis who are intolerant or not responding adequately to methotrexate. It may be used alone or in combination with methotrexate or other nonbiologic DMARDs. It should not be used with other JAK inhibitors (tofacitinib, baricitinib), biologic DMARDs, or other potent immunosuppressives (eg, azathioprine, cyclosporine).



Upon completion of the chapter, the reader will be able to:

  1. Identify risk factors for developing adult rheumatoid arthritis (RA) or juvenile idiopathic arthritis (JIA).

  2. Describe the pathophysiology of RA, with emphasis on the specific immunologic components.

  3. Discuss the comorbidities associated with RA.

  4. Recognize the typical clinical presentation of RA or JIA.

  5. Create treatment goals for a patient with RA or JIA.

  6. Compare the available pharmacotherapeutic options, selecting the most appropriate regimen for a given patient.

  7. Propose a patient education plan that includes nonpharmacologic and pharmacologic treatment measures.

  8. Formulate a monitoring plan to evaluate the safety and efficacy of a therapeutic regimen designed for an individual patient with RA or JIA.


Rheumatoid arthritis (RA) is a complex systemic inflammatory condition manifesting initially as symmetric swollen and tender joints of the hands and/or feet. Some patients may experience low disease activity, whereas others may present with high disease activity and/or extraarticular manifestations. The systemic inflammation of RA leads to joint destruction, disability, and premature death. Juvenile idiopathic arthritis (JIA) is the most common form of arthritis in children.


RA has a prevalence of 0.5% to 1%.1,2 Patients with RA have a 50% increased risk of premature death and a decreased life expectancy of 3 to 10 years compared with individuals without RA.3 The underlying causes of increased mortality are unclear. RA arises from an immunologic reaction, perhaps in response to a genetic or infectious antigen. Risk factors associated with the development of RA include the following:


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