Infliximab for psoriasis

doi:10.1016/S0190-9622(03)01143-5

Journal of the American Academy of Dermatology

Volume 49, Issue 2, Supplement, August 2003, Pages 112-117

https://doi.org/10.1016/S0190-9622(03)01143-5 Get rights and content

Abstract

This review summarizes the use of inflximab in psoriasis and other immune-mediated inflammatory disorders (IMIDs). The magnitude and speed of the response to infliximab monotherapy of moderate to severe psoriasis vulgaris is substantial, being similar to those achieved with cyclosporin. In contrast with cyclosporin, clinical improvement after the initial 3 intravenous influsions of infliximab is maintained for as long as 6 months in approximately half the patients with the absence of any additional treatment. Additionally, infliximab monotherapy normalizes keratinocyte proliferation and differentiation and markedly decreases epidermal inflammation. These results provide a convincing argument for the role of TNF-α in the pathogenesis of psoriasis and for the clinical development of infliximab for the treatment of psoriasis.

Section snippets

TNF-α is a proinflammatory cytokine

The inflammatory response in psoriatic plaques is initiated in part by activated T cells in the epidermis and dermis. T1 T cells predominate in plaques. These T cells release a number of inflammatory cytokines, including tumor necrosis factor-α (TNF-α). TNF-α, γ-interferon, interleukin (IL)-6, IL-8, IL-12, and other inflammatory cytokines are elevated in psoriatic lesions but not in the normal skin of psoriatic patients. TNF-α increases the synthesis of pro-inflammatory cytokines such as IL-1,

Chemical structure

Infliximab is a mouse/human chimeric antibody comprising a mouse variable region and a human IgG1/α constant region.24 It has a molecular weight of 149,100 Da, and a binding specificity for human TNF-α. It is administered to patients via IV infusion over 2 to 3 hours.

Mechanism of action

Infliximab interferes with the actions of TNF-α by directly binding to soluble and transmembrane TNF-α molecules in the plasma and the diseased tissue. Infliximab-bound TNF-α cannot bind to or activate the TNF-α receptor.24

Drug interactions

No drug interactions have been noted in clinical trials during which infliximab was taken concurrently with MTX, nonsteroidal inflammatory drugs, folic acid, corticosteroids, narcotics, antibiotics, antivirals, 6-mercaptopurine/azathioprine, and aminosalicylates.

Study design

A placebo-controlled, double-blind study by Chaudhari et al2 enrolled patients with a ≥6-month history of plaque-type psoriasis who were insensitive to treatment with topical corticosteroids and whose psoriasis covered at least 5% of the body. Patients were randomized to receive IV placebo (n=11), infliximab 5 mg/kg (n=11), or infliximab 10 mg/kg (n=11), infused over 2 hours and repeated after 2 and 6 weeks. Efficacy and other clinical/laboratory measures were recorded at screening, baseline,

Conclusion

The magnitude and speed of the response to infliximab therapy in initial studies have been substantial, being similar to those achieved with cyclosporin; however, in contrast with cyclosporin, improvements in PASI were maintained for as long as 6 months in approximately half the patients in the absence of any treatment after the initial 3 IV influsions of infliximab. Unlike cyclosporin, there was no targeted organ toxicity observed with infliximab treatment. Additionally, infliximab monotherapy

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Funding sources: Centocor, Inc, a COSAT grant from the Johnson and Johnson Focused Giving Program, general support of the Clinical Research Center by Merck, Inc, and a grant from the Dr David Ju Foundation.

Disclosure: Dr Gottlieb is both a consultant and investigator for Amgen, Centocor, Connetics, Biogen, Genentech, Xoma, Wyeth, Cellgate, Boeringer-Ingelheim, Quatrex, Pfizer, and Novartis. She is a consultant for Enanta, Celgene, Beiersdorf, and Roche Pharmaceuticals and an investigator for Aventis. Dr Gottlieb does not own any stock in these companies nor in any companies with which she has a business relationship.

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Infliximab for psoriasis☆