alle9 - janeusmle

[ArchivalUser]

A 55-year-old man with a long history of psoriasis and psoriatic arthritis comes to the office complaining of exacerbating disease despite ongoing treatment. He has been on methotrexate, 15 mg orally weekly for almost a year with no significant improvement, and his skin lesions have worsened lately. In the past he has been treated with cyclosporine, acitretin, ultraviolet therapy, and multiple topicals with some benefit. The disease keeps recurring, however, and the bouts of arthritis are getting worse with time. His past medical history is significant for end-stage renal disease and multiple nonmelanoma skin cancers. Physical examination reveals a well developed and well nourished man in mild distress from severe arthralgia. His blood pressure is 140/90 mm Hg, pulse is 70/min, and respiratory rate is 18/min. Large, geographic erythematous plaques with nonadherent scale are present on the trunk and extremities and throughout the scalp. Multiple interphalangeal joints on the hands are swollen and have a sausage-shaped appearance. There is moderate limitation of movement. After discussing treatment options with the patient, you decide to initiate a new medication, etanercept. Which of the following statements is correct regarding this treatment option?

A. Addition of etanercept will be beneficial for the skin lesions but will not alleviate the symptoms of arthritis
B. Although this treatment regimen will most likely improve symptoms, it will not affect progression of degenerative arthritis
C. Its mechanism of action involves tumor necrosis factor-alpha inhibition
D. It requires discontinuation of methotrexate
E. The patient will need additional blood work performed weekly to include fasting lipids

[ArchivalUser]

cc

[ArchivalUser]

The correct answer is C. Tumor necrosis factor-alpha and interleukin-1 are important mediators of inflammation and tissue damage in animal models of inflammatory arthritis and in patients with active psoriatic arthritis. Etanercept is a recombinant fusion protein of the soluble type II tumor necrosis factor receptor on a human IgG1 backbone. It potently and selectively binds tumor necrosis factor-alpha in the cellular microenvironment, thereby preventing tumor necrosis factor-alpha from interacting with membrane-bound tumor necrosis factor receptors on target cells. Studies in animal models of inflammatory arthritis suggest that tumor necrosis factor-alpha plays a more important role in promoting inflammation, whereas interleukin-1 is more important in causing cartilage and bone destruction. These differential actions have not been borne out in clinical trials, however, in which tumor necrosis factor-alpha blockers similarly reduce clinical signs and symptoms of psoriatic and slow radiographic evidence of disease progression. Etanercept recently has been approved by the United States Food and Drug Administration for the treatment of psoriatic arthritis.

It is incorrect that addition of etanercept will be beneficial for the skin lesions but will not alleviate the symptoms of arthritis (choice A). Etanercept has been proven to provide clinical relief of joint pain and cutaneous lesions of psoriasis in affected patients.

It is incorrect that this treatment regimen will most likely improve symptoms but not affect progression of degenerative arthritis (choice B). Published clinical trials have documented slowing of degenerative joint disease in patients with psoriatic arthritis as evidenced by radiographic studies.

Addition of etanercept does not require discontinuation of methotrexate (choice D). The drugs may be used simultaneously in patients with psoriatic arthritis, as shown in multiple clinical trials.

Etanercept does not require routine blood work to be performed during its use. The patient therefore will not need additional blood work performed weekly to include fasting lipids (choice E). Fasting lipids are monitored routinely in patients on systemic retinoid therapy, such as acitretin or isotretinoin.