Elsevier

The Lancet

Volume 366, Issue 9494, 15–21 October 2005, Pages 1367-1374
The Lancet

Articles
Infliximab induction and maintenance therapy for moderate-to-severe psoriasis: a phase III, multicentre, double-blind trial

https://doi.org/10.1016/S0140-6736(05)67566-6Get rights and content

Summary

Background

Tumour necrosis factor α (TNFα) is thought to play a part in the pathogenesis of psoriasis. We assessed the efficacy and safety of continuous treatment with infliximab, a monoclonal antibody that binds to and neutralises the activity of TNFα, in patients with psoriasis.

Methods

In this phase III, multicentre, double-blind trial, 378 patients with moderate-to-severe plaque psoriasis were allocated in a 4:1 ratio to receive infusions of either infliximab 5 mg/kg or placebo at weeks 0, 2, and 6, then every 8 weeks to week 46. At week 24, placebo-treated patients crossed over to infliximab treatment. Skin and nail signs of psoriasis were assessed using the psoriasis area and severity index (PASI) and nail psoriasis severity index (NAPSI), respectively. The primary endpoint, analysed on an intention-to-treat-basis, was the proportion of patients achieving at least a 75% improvement in PASI from baseline to week 10.

Findings

At week 10, 80% (242/301) of patients treated with infliximab achieved at least a 75% improvement from their baseline PASI (PASI 75) and 57% (172/301) achieved at least a 90% improvement (PASI 90), compared with 3% and 1% in the placebo group, respectively (p<0·0001). At week 24, PASI 75 (82% for infliximab vs 4% for placebo) and PASI 90 (58% vs 1%) were maintained (p<0·0001). At week 50, 61% achieved PASI 75 and 45% achieved PASI 90 in the infliximab group. Infliximab was generally well tolerated in most patients.

Interpretation

Infliximab is effective in both an induction and maintenance regimen for the treatment of moderate-to-severe psoriasis, with a high percentage of patients achieving sustained PASI 75 and PASI 90 improvement through 1 year.

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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