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Background: Early clinical studies suggested that the anti-interleukin-17 receptor A monoclonal antibody brodalumab has efficacy in the treatment of psoriasis., Methods: In two phase 3 studies (AMAGINE-2 and AMAGINE-3), patients with moderate-to-severe psoriasis were randomly assigned to receive brodalumab (210 mg or 140 mg every 2 weeks), ustekinumab (45 mg for patients with a body weight ≤100 kg and 90 mg for patients >100 kg), or placebo. At week 12, patients receiving brodalumab were randomly assigned again to receive a brodalumab maintenance dose of 210 mg every 2 weeks or 140 mg every 2 weeks, every 4 weeks, or every 8 weeks; patients receiving ustekinumab continued to receive ustekinumab every 12 weeks, and patients receiving placebo received 210 mg of brodalumab every 2 weeks. The primary aims were to evaluate the superiority of brodalumab over placebo at week 12 with respect to at least a 75% reduction in the psoriasis area-and-severity index score (PASI 75) and a static physician's global assessment (sPGA) score of 0 or 1 (clear or almost clear skin), as well as the superiority of brodalumab over ustekinumab at week 12 with respect to a 100% reduction in PASI score (PASI 100)., Results: At week 12, the PASI 75 response rates were higher with brodalumab at the 210-mg and 140-mg doses than with placebo (86% and 67%, respectively, vs. 8% [AMAGINE-2] and 85% and 69%, respectively, vs. 6% [AMAGINE-3]; P<0.001); the rates of sPGA scores of 0 or 1 were also higher with brodalumab (P<0.001). The week 12 PASI 100 response rates were significantly higher with 210 mg of brodalumab than with ustekinumab (44% vs. 22% [AMAGINE-2] and 37% vs. 19% [AMAGINE-3], P<0.001). The PASI 100 response rates with 140 mg of brodalumab were 26% in AMAGINE-2 (P=0.08 for the comparison with ustekinumab) and 27% in AMAGINE-3 (P=0.007). Rates of neutropenia were higher with brodalumab and with ustekinumab than with placebo. Mild or moderate candida infections were more frequent with brodalumab than with ustekinumab or placebo. Through week 52, the rates of serious infectious episodes were 1.0 (AMAGINE-2) and 1.3 (AMAGINE-3) per 100 patient-years of exposure to brodalumab., Conclusions: Brodalumab treatment resulted in significant clinical improvements in patients with moderate-to-severe psoriasis. (Funded by Amgen; AMAGINE-2 and AMAGINE-3 ClinicalTrials.gov numbers, NCT01708603 and NCT01708629.).

Background: Hidradenitis suppurativa (HS) is a chronic, painful skin disease characterized by abscesses, nodules, and draining fistulas in the axilla and groin of young adults., Objective: To evaluate the efficacy and safety of adalimumab, an anti-tumor necrosis factor-α antibody, in patients with moderate to severe HS., Design: Phase 2, parallel, randomized, placebo-controlled trial consisting of a blinded 16-week period (period 1) and an open-label 36-week period (period 2). All study personnel, investigators, and patients remained blinded to treatment group throughout the study. (ClinicalTrials.gov: NCT00918255), Setting: 26 academic and private practice medical centers in the United States and Europe., Patients: 154 adult patients with moderate to severe HS who were unresponsive or intolerant to oral antibiotics., Intervention: Patients were assigned in a 1:1:1 ratio to adalimumab, 40 mg/wk; adalimumab, 40 mg every other week (EOW); or placebo. All patients received adalimumab, 40 mg EOW, at the beginning of period 2 but switched to weekly dosing if the response was suboptimal (HS Physician's Global Assessment [PGA] score of moderate or worse) at weeks 28 or 31., Measurements: The primary outcome measure (clinical response) was the proportion of patients achieving an HS-PGA score of clear, minimal, or mild with at least a 2-grade improvement relative to baseline at week 16., Results: At week 16, 3.9% of placebo patients (2 of 51), 9.6% of EOW patients (5 of 52), and 17.6% of weekly patients (9 of 51) achieved clinical response (EOW vs. placebo strata-adjusted difference, 5.6% [95% CI, -4.0% to 15.3%]; P = 0.25; weekly vs. placebo strata-adjusted difference, 13.7% [CI, 1.7% to 25.7%]; P = 0.025). Serious adverse event rates were 3.9%, 5.8%, and 7.8% for placebo, EOW, and weekly patients, respectively (EOW vs. placebo difference, 1.8% [CI, -6.4% to 10.1%]; weekly vs. placebo difference, 3.9% [CI, -5.2% to 13.0%]). Significantly greater improvements in patient-reported outcomes and pain were seen in the weekly dosing group than in the placebo group. A decrease in response was seen after the switch from weekly to EOW dosing in period 2., Limitations: Weeks 16 to 52 of the study were open-label. The study was not powered to assess the risk for known serious adverse effects of adalimumab, such as tuberculosis, other serious infections, and demyelinating disorders., Conclusion: Adalimumab dosed once per week alleviates moderate to severe HS., Primary Funding Source: Abbott Laboratories.

Background: The anti-interleukin-12/23p40 monoclonal antibody briakinumab has been shown in a phase II study to be effective psoriasis treatment., Objectives: The aim of the current study was to assess the efficacy, safety and tolerability of briakinumab compared with etanercept and placebo in patients with moderate to severe chronic plaque psoriasis., Methods: In this phase III, 12-week study (M10-114, NCT00691964), 347 patients were randomized in a 2 : 2 : 1 ratio to receive 200 mg briakinumab at weeks 0 and 4 followed by 100 mg briakinumab at week 8 (n = 138); 50 mg of etanercept twice weekly 3-4 days apart at weeks 0-11 (n = 141); or placebo injections matching active treatment (n = 68). The co-primary efficacy endpoints were the proportion of patients achieving a Physician's Global Assessment (PGA) of 0/1 at week 12, and the proportion of patients achieving a Psoriasis Area and Severity Index (PASI) 75 response at week 12., Results: Of the briakinumab-treated patients, 71·0% achieved a PGA of 0/1 at week 12 as compared with 39·7% of etanercept-treated patients and 2·9% of placebo-treated patients, (P < 0·001, for both comparisons). Of the briakinumab-treated patients 81·9% achieved a PASI 75 response at week 12 as compared with 56·0% of etanercept-treated and 7·4% of placebo-treated patients (P < 0·001, for both comparisons). Serious adverse event rates were reported in four (2·9%) patients receiving briakinumab, one (0·7%) patient receiving etanercept and one (1·5%) placebo-treated patient., Conclusions: In patients with moderate to severe psoriasis, briakinumab had superior efficacy to both placebo and etanercept at 12 weeks as administered in this study., (© 2011 The Authors. BJD © 2011 British Association of Dermatologists.)

Background: Psoriasis is a common chronic relapsing, inflammatory, hyperproliferative skin disorder with genetic predisposition. There is currently no experimental model for psoriasis and the pathogenesis is not fully understood. Psoriatic plaques have been shown to contain increased levels of cytokines, including tumor necrosis factor alpha (TNF-alpha). Anti-tumor necrosis factor therapy with infliximab has been shown to be highly effective in recalcitrant psoriasis., Methods: We evaluated the efficacy and timeline of histological changes in a psoriatic plaque following infliximab infusion. A patient with severe recalcitrant plaque psoriasis was clinically and histologically assessed for improvement., Results: We found rapid clinical improvement with infliximab accompanied by histopathological changes. The earliest effects were seen on neutrophils and lymphocytes whereas keratinocyte normalization was not evident at the early stages., Conclusion: Infliximab is not only an effective agent in the treatment of psoriasis but appears to have a very rapid onset of action.

This report describes the case of a patient with erythrodermic psoriasis who had failed all previous therapies and been hospitalized numerous times over a 12-year period that responded dramatically to treatment with infliximab. The potential utility of infliximab as a therapeutic alternative for erythrodermic psoriasis is discussed.

Background: Hidradenitis suppurativa (HS) is a chronic disease characterized by significant morbidity. Current medical therapies are only minimally effective at treating the disease. Infliximab is a chimeric monoclonal antibody with high affinity for tumour necrosis factor (TNF)-alpha. TNF-alpha is known to induce proinflammatory cytokines and may play an important role in the therapy of a number of disparate inflammatory disorders. Infliximab has shown promise for the therapy of rheumatoid arthritis and psoriasis., Objectives: Retrospectively to evaluate the effectiveness of infliximab for the treatment of HS., Methods: A retrospective chart review was performed for patients who received infliximab at the University of Miami Department of Dermatology. Patients were contacted and asked retrospectively to rate their disease activity immediately prior to and after therapy., Results: Patients' self-reported disease activity scores were significantly decreased (P = 0.0001, paired t-test) following infliximab infusion. This correlated with physician-observed clinical improvement., Conclusions: Infliximab is a promising agent for the treatment of HS. These initial results suggest that infliximab is associated with objective and subjective improvement in HS. Further controlled studies of the efficacy of infliximab and its effect on the course of the disease are warranted.

Tumor necrosis factor-alpha (TNF-alpha) is a chemokine secreted by T cells which is thought to play a critical role in the pathophysiology of psoriasis. The monoclonal antibody, infliximab, complexes with TNF-alpha, rendering it inactive. A recent clinical trial has reported the clinical benefit and safety of infliximab in moderate to severe plaque psoriasis. We report a case of rapid response and clinical benefit using infliximab in severe pustular psoriasis of von Zumbusch.