Report from the fourth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative).

This article is a report of the fourth meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in Malmö, Sweden on 23-24 April 2015 (HOME IV). The aim of the meeting was to achieve consensus over the preferred outcome instruments for measuring patient-reported symptoms and quality of life for the HOME core outcome set for atopic eczema (AE). Following presentations, which included data from systematic reviews, consensus discussions were held in a mixture of whole group and small group discussions. Small groups were allocated a priori to ensure representation of different stakeholders and countries. Decisions were voted on using electronic keypads. For the patient-reported symptoms, the group agreed by vote that itch, sleep loss, dryness, redness/inflamed skin and irritated skin were all considered essential aspects of AE symptoms. Many instruments for capturing patient-reported symptoms were discussed [including the Patient-Oriented SCOring Atopic Dermatitis index, Patient-Oriented Eczema Measure (POEM), Self-Administered Eczema Area and Severity Index, Itch Severity Scale, Atopic Dermatitis Quickscore and the Nottingham Eczema Severity Score] and, by consensus, POEM was selected as the preferred instrument to measure patient-reported symptoms. Further work is needed to determine the reliability and measurement error of POEM. Further work is also required to establish the importance of pain/soreness and the importance of collecting information regarding the intensity of symptoms in addition to their frequency. Much of the discussion on quality of life concerned the Dermatology Life Quality Index and Quality of Life Index for Atopic Dermatitis; however, consensus on a preferred instrument for measuring this domain could not be reached. In summary, POEM is recommended as the HOME core outcome instrument for measuring AE symptoms.

Long-term efficacy and safety of infliximab maintenance therapy in patients with plaque-type psoriasis in real-world practice.

BACKGROUND: Tumour necrosis factor-α inhibitors, including infliximab (IFX), can improve disease control of plaque-type psoriasis. OBJECTIVES: The Real-World Assessment of Long-Term Infliximab Therapy for Psoriasis (REALITY) study evaluated the efficacy and safety of maintenance IFX therapy in typical clinical settings. METHODS: In this prospective, observational, open-label, multicentre study in patients with plaque-type psoriasis, IFX 5 mg kg was infused at weeks 0, 2 and 6, and every 8 weeks thereafter during a 50-week treatment phase. The primary outcome was ≥ 75% Psoriasis Area and Severity Index (PASI) improvement from baseline to week 50. Patients with ≥ 25% PASI improvement from baseline to the end of the treatment phase were potentially eligible to enter a 48-week extended treatment phase. Response maintenance and other efficacy measures were evaluated. Adverse events (AEs) were collected. RESULTS: In total 660 patients enrolled. Of 521 efficacy-evaluable treatment phase patients (66% male, mean age 46·5 years, mean PASI 18·1), 56·8% achieved PASI 75 at the end of the treatment phase. Response was maintained at week 50 by 64·7% (205/317) of patients who achieved PASI 75 at week 14. During extended treatment, 66·3% (112/169) of patients attained PASI 75 at week 98; response was maintained at week 98 by 71·6% (101/141) of those who achieved PASI 75 at week 50. IFX was generally well tolerated. During treatment, 7·6% (50/659) of patients had serious AEs. During extended treatment, 4·1% (eight of 193) of patients had serious AEs. CONCLUSIONS: PASI 75 response was achieved by 56·8% and 66·3% of patients at weeks 50 and 98, respectively. The AE pattern was consistent with previous reports.

Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways.

BACKGROUND: Psoriasis vulgaris is an inflammatory skin disease mediated by Th1 and Th17 cytokines, yet the relative contribution of interferon (IFN)-gamma, interleukin (IL)-17 and IL-22 on disease pathogenesis is still unknown. OBJECTIVES: In this study, we sought to identify the cytokines produced by skin-resident T cells in normal skin, localize the receptors for these cytokines, and examine how these cytokines alter gene expression profiles of the cells bearing cognate receptors. METHODS: We used intracellular cytokine staining and flow cytometry to evaluate T cell cytokine production, and immunohistochemistry and double-label immunofluorescence to localize cytokine receptors in skin. Gene array analysis of cytokine-treated keratinocytes was performed using moderated paired t-test controlling for false discovery rate using the Benjamini-Hochberg procedure. RESULTS: We demonstrate that T-helper cells producing IL-17, IL-22 and/or IFN-gamma, as well as the cells bearing cognate cytokine receptors, are present in normal human skin. Keratinocytes stimulated with IL-17 expressed chemokines that were different from those induced by IFN-gamma, probably contributing to the influx of neutrophils, dendritic cells and memory T cells into the psoriatic lesion. In contrast, IL-22 downregulated genes associated with keratinocyte differentiation and caused epidermal alterations in an organotypic skin model. CONCLUSIONS: Our results suggest that the Th17 cytokines IL-17 and IL-22 mediate distinct downstream pathways that contribute to the psoriatic phenotype: IL-17 is more proinflammatory, while IL-22 retards keratinocyte differentiation.