Infliximab (Remicade) in the treatment of psoriatic arthritis

Abstract

Elucidation of the cellular immunopathology and cytokine profile of psoriatic arthritis (PsA), a chronic inflammatory disease associated with psoriasis, has resulted in the development of a number of novel biologic therapies. Among these biologics, tumor necrosis factor-alpha (TNF-alpha) inhibitors have been used successfully to treat patients suffering from rheumatoid arthritis or psoriasis. The pivotal role of TNF-alpha in the pathogenesis and progression of PsA suggested that anti-TNF-alpha agents could be effective in controlling PsA. The results from two large, randomized, double-blind, placebo-controlled trials in patients with moderate to severe PsA indicated that the anti-TNF-inhibitor, infliximab, can control both the joint and skin manifestations of the disease. This review focuses on the clinical development of infliximab as a treatment for PsA. The development of other anti-TNF-alpha biologics is also discussed.

Figure 1

The inflammatory response cascade induced by tumor necrosis factor-α (TNF-α) manifesting in joint destruction. Copyright © 2005. Reproduced from Mease PJ, Goffe BS, Metz J, et al. 2000. Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomised trial. Lancet, 356:385–90. TNF-α binding stimulates mononuclear phagocytes to secrete the pro-inflammatory cytokines interleukin (IL)-1, IL-6, and granulocyte macrophage–colony stimulating factor (GM-CSF).These cytokines promote recruitment of T-cells into afflicted joints and also stimulate proliferation of osteoclasts, synovial fibroblasts and chondrocytes at these sites.The resultant inflammatory responses, coupled with release of metalloproteinases and other effector molecules by activated cells, results in joint destruction.

Figure 2

Percentages of patients achieving improvement by the American College of Rheumatology 20% (ACR20) criteria for improvement in rheumatoid arthritis through week 50. Results from the Phase III, IMPACT trial that assessed the effectiveness of infliximab for treating psoriatic arthritis. Copyright © 2005. Reproduced with permission from Antoni CE, Kavanaugh A, Kirkham B, et al. 2005. Sustained benefits of infliximab therapy for dermatologic and articular manifestations of psoriatic arthritis: results from the infliximab multinational psoriatic arthritis controlled trial (IMPACT). Arthritis Rheum, 52:1227–36. Arrows indicate weeks at which infusions were administered: open arrows denote placebo (Pbo) infusions, and solid arrows denote infusions of infliximab (Inf) 5 mg/kg.

Figure 3

Psoriasis Area and Severity Index (PASI) scores (mean and SD) at baseline, week 16, and week 50 in patients who had a PASI score of ≥2.5 at baseline. Results from the Phase III, IMPACT trial that assessed the effectiveness of infliximab for treating PsA. Copyright © 2005. Reproduced with permission from Antoni CE, Kavanaugh A, Kirkham B, et al. 2005. Sustained benefits of infliximab therapy for dermatologic and articular manifestations of psoriatic arthritis: results from the infliximab multinational psoriatic arthritis controlled trial (IMPACT). Arthritis Rheum, 52:1227–36.