The response of psoriasis to antibodies targeting the interleukin (IL)-23/IL-17A pathway suggests a prominent role of T-helper type-17 (Th17) cells in this disease. We examined the clinical and immunological response patterns of 100 subjects with moderate-to-severe psoriasis receiving 3 different intravenous dosing regimens of the anti-IL-17A antibody secukinumab (1 × 3 mg/kg or 1 × 10 mg/kg on Day 1, or 3 × 10 mg/kg on Days 1, 15 and 29) or placebo in a phase 2 trial. Baseline biopsies revealed typical features of active psoriasis, including epidermal accumulation of neutrophils and formation of microabscesses in >60% of cases. Neutrophils were the numerically largest fraction of infiltrating cells containing IL-17 and may store the cytokine preformed, as IL-17A mRNA was not detectable in neutrophils isolated from active plaques. Significant clinical responses to secukinumab were observed 2 weeks after a single infusion, associated with extensive clearance of cutaneous neutrophils parallel to the normalization of keratinocyte abnormalities and reduction of IL-17-inducible neutrophil chemoattractants (e.g. CXCL1, CXCL8); effects on numbers of T cells and CD11c-positive dendritic cells were more delayed. Histological and immunological improvements were generally dose dependent and not observed in the placebo group. In the lowest-dose group, a recurrence of neutrophils was seen in some subjects at Week 12; these subjects relapsed faster than those without microabscesses. Our findings are indicative of a neutrophil–keratinocyte axis in psoriasis that may involve neutrophil-derived IL-17 and is an early target of IL-17A-directed therapies such as secukinumab.
Background: Psoriasis severity categories have been important tools for clinicians to use in treatment decisions as well as to determine eligibility criteria for clinical studies. However, owing to the heterogeneity of severity classifications and their lack of consideration for the impact of psoriasis involvement of special areas or past treatment history, patients may be miscategorized, which can lead to undertreatment of psoriasis.Objective: To develop a consensus statement on the classification of psoriasis severity.Methods: A modified Delphi approach was developed by the International Psoriasis Council to define psoriasis severity.Results: After completion of the exercise, 7 severity definitions were preferentially ranked. This most preferred statement rejects the mild, moderate, and severe categories in favor of a dichotomous definition: Psoriasis patients should be classified as either candidates for topical therapy or candidates for systemic
Background: Effective and safe products are needed for long-term management of scalp psoriasis. This study investigated the long-term safety and efficacy of a two-compound formulation (calcipotriol 50 µg/g plus betamethasone dipropionate 0.5 mg/g) for scalp psoriasis. Methods: In this 52-week, international, double-blind study, 869 patients with moderate-to-severe scalp psoriasis were randomized to either a two-compound scalp formulation (n = 429) or calcipotriol (n = 440). Results: Adverse drug reactions were less frequent in the two-compound group compared with the calcipotriol group (17.2 vs. 29.5%; p < 0.001). Incidences of adverse events possibly associated with long-term corticosteroid use were low in both the two-compound (2.6%) and the calcipotriol (3.0%) groups. Disease was satisfactorily controlled in 92.3% of visits in the two-compound group versus 80.0% in the calcipotriol group (p < 0.001). Conclusion: The two-compound scalp formulation demonstrated a high level of safety and efficacy in long-term management of scalp psoriasis.
These statements and recommendations will serve to increase awareness of HS and provide a framework for decisions involving diagnosis and management. Evidence suggests that antibacterial and anti-tumour necrosis factor therapies are effective in the treatment of HS. This is supported by the clinical experience of the authors. Further clinical research and the establishment of multidisciplinary management teams will continue to advance management of HS in Canada.
Engaging global key opinion leaders, the International Psoriasis Council (IPC) held a day-long roundtable discussion with the primary purpose to discuss the treatment goals of psoriasis patients and worldwide barriers to optimal care. Setting clear expectations might ultimately encourage undertreated psoriasis patients to seek care in an era in which great gains in therapeutic efficacy have been achieved. Here, we discuss the option for early treatment of all categories of psoriasis to alleviate disease impact while emphasizing the need for more focused attention for psoriasis patients with mild and moderate forms of this autoimmune disease. In addition, we encourage policy changes to keep pace with the innovative therapies and clinical science and highlight the demand for greater understanding of treatment barriers in resource-poor countries.
Ustekinumab significantly improves nail psoriasis, and improvements continue over time until up to 1 year of treatment in those receiving maintenance treatment.
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