ArticlesInfliximab induction and maintenance therapy for moderate-to-severe psoriasis: a phase III, multicentre, double-blind trial
Introduction
Psoriasis is a chronic, immunologically based, inflammatory skin disease, of which plaque-type psoriasis is the most common form.1, 2 Cytokines released from cutaneous antigen-presenting cells, T cells, and keratinocytes are believed to play a key part in the formation of plaques in psoriasis.3, 4 Biological treatments that target cytokines represent a new option for the management of the disease.5 Tumour necrosis factor α (TNFα), a key mediator in many inflammatory diseases, is thought to have an important role in the pathogenesis of psoriasis. In a novel mouse model, it has been shown that TNFα is the primary cytokine mediating the activation and proliferation of resident T cells, which are essential in the development of psoriasis lesions.6 Increased concentrations of TNFα have been recorded in the serum samples7 and skin lesions of patients with psoriasis,8, 9, 10 and serum concentrations of TNFα have been shown to correlate with disease activity.11
Infliximab, a monoclonal antibody that binds with high affinity and specificity to TNFα and neutralises its biological activity, is approved for the treatment of other chronic diseases characterised by TNFα-mediated inflammation, such as rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, and psoriatic arthritis. Early studies have identified biological effects and clinical activity in psoriasis.12, 13 Here, we present the results of a phase III study, addressing the long-term safety and efficacy of infliximab for the treatment of skin and nail lesions in patients with psoriasis. Additional information was obtained on the potential effect of antibodies to infliximab and serum concentrations of infliximab on maintenance of the therapeutic response.
Section snippets
Patients
Of 472 adult patients who were screened, 378 were enrolled at 32 centres in this phase III, multicentre, double-blind, placebo-controlled trial. Institutional review board or ethics committee approval and written informed consent were obtained before any protocol-specific procedures were undertaken. Patients had a diagnosis of moderate-to-severe plaque-type psoriasis for at least 6 months, were candidates for phototherapy or systemic therapy, had a psoriasis area and severity index (PASI) score
Results
Of the 378 enrolled patients, 77 were allocated to placebo and 301 to infliximab 5 mg/kg (figure 1). The treatment groups were generally well balanced with respect to demographics, baseline disease characteristics, and previous anti-psoriasis treatment (table 1). For the pre-specified analyses, the maximum number of patients included was 301 in the infliximab group and 77 in the placebo to infliximab group (at week 50, n=281 and 68, respectively). For the per protocol analysis, the maximum
Discussion
In this phase III study of infliximab in patients with moderate-to-severe psoriasis, we show the high efficacy, rapid onset, and long-term maintenance of therapeutic response for skin as well as nail lesions. Maintenance of therapeutic response seemed to be related to the achievement of stable serum infliximab concentrations and was more common in patients negative for antibodies to infliximab than in antibody-positive patients. These data establish intravenous infliximab monotherapy as an
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Investigators are listed at the end of the report