Thomas Anton Luger

BACKGROUND: Two phase 3 trials (UNCOVER-2 and UNCOVER-3) showed that at 12 weeks of treatment, ixekizumab, a monoclonal antibody against interleukin-17A, was superior to placebo and etanercept in the treatment of moderate-to-severe psoriasis. We report the 60-week data from the UNCOVER-2 and UNCOVER-3 trials, as well as 12-week and 60-week data from a third phase 3 trial, UNCOVER-1.

METHODS: We randomly assigned 1296 patients in the UNCOVER-1 trial, 1224 patients in the UNCOVER-2 trial, ...

Intercellular adhesion molecule-1 (ICAM-1) is involved in cell-cell interactions of leukocytes and parenchymal cells and thus plays an important role in immunologic and inflammatory reactions. The expression of ICAM-1 that is found on many different cells such as melanocytes and melanoma cells is induced by various cytokines, including interferon-gamma (IFN gamma), interleukin (IL)-1 and tumor necrosis factor alpha (TNF alpha). Because expression of ICAM-1 in melanoma was found to ...

Irradiation with ultraviolet (UV) B radiation results in the formation of apoptotic keratinocytes called sunburn cells. Recently, it was demonstrated that keratinocytes can release tumor necrosis factor-alpha (TNF-alpha), which is known to cause apoptosis in particular cells. In addition, it has been shown that UVB light induces the release of TNF-alpha by keratinocytes and that keratinocytes express the 55-kD receptor for TNF-alpha. Therefore, we investigated whether TNF-alpha is ...

BACKGROUND: In previous studies, etanercept 25 mg twice weekly (BIW) or 50 mg BIW significantly reduced disease severity in patients with plaque psoriasis and demonstrated a favourable safety profile.

OBJECTIVES: To assess the efficacy and safety of etanercept 50 mg administered once weekly (QW) compared with placebo in patients with moderate-to-severe plaque psoriasis over 24 weeks.

METHODS: This study was conducted in two parts: (i) a 12-week, double-blind, placebo-controlled phase, in ...

BACKGROUND: Secukinumab, a fully human monoclonal antibody that selectively neutralizes IL-17A, has been shown to have significant efficacy and a favourable safety profile in the treatment of moderate-to-severe psoriasis and psoriatic arthritis.

OBJECTIVE: To assess the efficacy and safety of secukinumab through 5 years of treatment in moderate-to-severe psoriasis.

METHODS: In the core SCULPTURE study, Psoriasis Area and Severity Index (PASI) 75 responders at Week 12 continued receiving ...

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor being investigated for psoriasis.

OBJECTIVES: To determine the 16-week efficacy and safety of two oral tofacitinib doses vs. placebo in patients with moderate-to-severe chronic plaque psoriasis.

METHODS: Patients in two similarly designed phase III studies (OPT Pivotal 1, NCT01276639, n = 901; OPT Pivotal 2, NCT01309737, n = 960) were initially randomized 2 : 2 : 1 to tofacitinib 10 or 5 mg or placebo, twice daily. Coprimary ...

The skin is a known target organ for the proopiomelanocortin (POMC)-derived neuropeptides alpha-melanocyte stimulating hormone (alpha-MSH), beta-endorphin, and ACTH and also a source of these peptides. Skin expression levels of the POMC gene and POMC/corticotropin releasing hormone (CRH) peptides are not static but are determined by such factors as the physiological changes associated with hair cycle (highest in anagen phase), ultraviolet radiation (UVR) exposure, immune cytokine ...

Induction of apoptosis in keratinocytes by UV light is a critical event in photocarcinogenesis. Although p53 is of importance in this process, evidence exists that other pathways play a role as well. Therefore, we studied whether the apoptosis-related surface molecule CD95 (Fas/APO-1) is involved. The human keratinocyte cell line HaCaT expresses CD95 and undergoes apoptosis after treatment with UV light or with the ligand of CD95 (CD95L). Incubation with a neutralizing CD95 antibody ...

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a new member of the tumor necrosis factor (TNF) family, induces apoptosis primarily of transformed cells. Interleukin-1 was previously found to protect the keratinocyte cell line KB from TRAIL-induced apoptosis, thus we studied whether interleukin-1 also protects from other apoptotic stimuli (ultraviolet radiation (UV), CD95-ligand). Interleukin-1 rescued KB cells from TRAIL- and CD95-induced apoptosis, which was critically ...

BACKGROUND: Since the publication of the European League Against Rheumatism recommendations for the pharmacological treatment of psoriatic arthritis (PsA) in 2012, new evidence and new therapeutic agents have emerged. The objective was to update these recommendations.

METHODS: A systematic literature review was performed regarding pharmacological treatment in PsA. Subsequently, recommendations were formulated based on the evidence and the expert opinion of the 34 Task Force members. ...

Proteinase-activated receptor 2 belongs to a new G protein-coupled receptor subfamily activated by various serine proteases. It has been demonstrated to play a role during inflammation of many tissues including the skin. Proteinase-activated receptor 2 is expressed by endothelial cells and regulates cutaneous inflammation in vivo. The underlying mechanisms of proteinase-activated receptor 2 activation in the skin and the effects on human dermal microvascular endothelial cells, however, ...

OBJECTIVE: Recently, we found that human dermal fibroblasts (HDFs) express melanocortin 1 receptors (MC-1R) that bind alpha-melanocyte-stimulating hormone (alpha-MSH). In search of novel therapies for scleroderma (systemic sclerosis [SSc]), we used the bleomycin (BLM) model to investigate the effects of alpha-MSH on collagen synthesis and fibrosis.

METHODS: Collagen expression in HDFs was determined by real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blot ...

Pentoxifylline (PTX) is a methylxanthine compound known to inhibit the production of tumour necrosis factor-alpha (TNF-alpha), which is an important inflammatory mediator. There is also recent evidence that PTX may influence other inflammatory cytokines, such as interleukin-1 (IL-1) and IL-6. Due to the therapeutic implications, the present study addressed the in vivo effects of PTX on the release of TNF-alpha, IL-1 beta, IL-6 and IL-8 by human peripheral blood mononuclear cells (PBMC). ...