Tumour necrosis factor (TNF) in psoriatic arthritis: pathophysiology and treatment with TNF inhibitors

Abstract

High levels of proinflammatory cytokines, including tumour necrosis factor (TNF), have been detected in psoriatic skin lesions and joints of patients with the inflammatory disease. Early results of treatment of psoriatic arthritis and psoriasis with TNF neutralising agents are encouraging, but whether these agents will be able to improve long term outcomes, such as disability, is not yet known.

Figure 1

Distal interphalangeal joint involvement in the fingers of a patient with arthritis mutilans, a severe form of psoriatic arthritis.

Figure 2

Tumour necrosis factor (TNF) expression in a synovial membrane section from an affected joint of a patient with a severe form of psoriatic arthritis, arthritis mutilans (original magnification x600). The section was stained with a monoclonal antibody to TNF. Reproduced from Danning et al, 2000²⁷ with permission.

Figure 3

Neutralisation of TNF by soluble TNF receptors (sTNFR) or anti-TNF monoclonal antibody (mAb) prevents TNF binding to either the p55 or the p75 receptors.^{47, 64–67}

Figure 4

Clinical response as assessed by Psoriatic Arthritis Response Criteria (PsARC) in patients with PsA treated with etanercept or placebo. Adapted from Mease 2000¹ with permission.

Figure 5

Clinical response as assessed by American College of Rheumatology (ACR) criteria in patients with PsA treated with etanercept or placebo. ACR 20, 50, and 70 responses are defined as ≥20%, ≥50%, and ≥70% reductions, respectively, in tender and swollen joint counts and in three or more of the following: patient pain assessment, patient global assessment, doctor global assessment, patient disability assessment, and C reactive protein level. Adapted from Mease 2000¹ with permission.