Viewpoint on handling anti-TNF failure in psoriasis

An association among the occurrence of antidrug antibodies (ADAs), diminished trough serum drug levels (TSDLs) and non-response or loss of response has been described for several tumor necrosis factor alpha (TNF) blocking agents in a variety of diseases, including psoriasis. In a series of ten psoriasis patients with primary or secondary failure, or adverse reactions during anti-TNF therapy, we measured ADAs and TSDLs in patient serum using radioimmunoassay and ELISA, respectively. By proposing a treatment algorithm derived from research in this field, we show that measuring ADAs and TSDLs in psoriasis patients provides a more structured approach to clinical decision making for psoriasis patients who fail anti-TNF therapy

Towards personalised medicine in psoriasis

Psoriasis is a chronic inflammatory disease of the skin with a strong genetic basis. In the past decade, great leaps have been made in understanding the molecular basis of psoriasis, and with this new knowledge, better treatment options were introduced for those with recalcitrant psoriasis. However, despite the plethora of new treatment options and biologics to treat the most difficult cases of psoriasis, dermatologists are still confronted with the heterogeneity of treatment effects for psoriasis in the area of treatment response as well as adverse drug effects. The field of personalised medicine is still nascent but holds much promise for chronic debilitating diseases like psoriasis. The ultimate goal of personalised medicine in psoriasis is allowing clinicians to predict who will get the disease, whether it will be a short benign or long debilitating course and who will get complications from the disease. More importantly, it will allow clinicians to better tailor treatment options for patients, avoiding drug toxicities and achieving long-term remission for patients. Personalised medicine includes a broad interdisciplinary research area (including both basic and applied approaches) and consequently various approaches can be pursued to personalise medicine. The primary aim of this thesis was to explore several strategies that could ultimately lead to personalised care for psoriasis patients. Since RNAi is a promising tool to personalise treatments, we explored the potential of RNAi-mediated gene suppression as a new targeted, patient-friendly topical therapy for psoriasis patients. To this end, preclinical models systems (in vitro and in vivo) were developed, which are indispensable tools in the discovery and development process of new drugs. We show the potential of a formulation consisting of siRNA-containing liposomes to deliver a specific siRNA to the epidermis of a skin humanised-mouse model for psoriasis and to inhibit psoriasis-specific genes. Our proposed models will serve to validate other strategies in therapeutic development in the future. Another goal was to optimise the current use of biologics in psoriasis. Therefore, we explored the usefulness of measuring anti-drug antibodies and serum trough levels to guide a clinician’s decisions making when dealing with non-response or adverse reactions to biologics. We provide a treatment paradigm, which can serve as a tool to personalise treatment for psoriasis patients treated with certain biologics. Biomarkers are of increasing importance for personalised medicine, with applications including diagnosis, prognosis, and selection of targeted therapies. In this work, we describe the detection of a miRNA signature in whole blood of patients, which could serve as a molecular signature of the disease. It is our aim to check in the future whether this signature can be used to predict phenotype evolution, and/or response to certain treatment. In conclusion, with this work we provide a first step into possible ways to personalised care for psoriasis patients. Future research will be necessary to assess the usefulness and clinical utility of these different strategies

An educational programme for patients with psoriasis and atopic dermatitis: a prospective randomized controlled trial

Background:  Patient education as an addition to standard treatment, with the aim of affecting care through courses is a relatively new concept in dermatology. Here we introduce a randomized controlled trial (RCT) with regard to a previously described 12 week educational programme for chronic skin diseases. Objective:  The primary objective of the RCT was to measure the effect of an educational programme on disease severity and quality of life in patients with psoriasis or atopic dermatitis. Methods:  We recruited 50 patients at from the Ghent University Hospital. Patients with diagnosed psoriasis or atopic dermatitis were randomised (1:1) to the intervention or control group. Clinical outcome was measured by 2 blinded observers using 'Psoriasis Area and Severity Index' or 'Scoring Atopic Dermatitis' and 'Eczema Area and Severity Index'. Quality of life was measured by dermatology-specific quality of life questionnaires. There was a follow-up period of 9 months. Results:  We found that disease severity and quality of life improved significantly for psoriasis patients (n=29) but not for atopic dermatitis patients (n=21) at 3 months. Intervention patients showed a significant reduction in mean PASI (p=0.036), in mean Dermatology Life Quality Index (p=0.019) and in mean Psoriasis Disability Index (p=0.015) compared with the control group at 3 months. This improvement continued for at least 6 months, i.e. 3 months after the intervention but was lost at 9 months follow-up. Conclusion:  Evaluating this form of educational programme, through means of a single-centre RCT, indicates its added value in the longer term management of psoriasis

Ambassadeurs van de integriteitsgedachte: de aanpak van de Universiteit Gent

Of het nu gaat om BAMA-studenten, jonge onderzoekers, startende professoren of administratief personeel – de Universiteit Gent vindt dat alle geledingen scholing behoeven in wetenschappelijke integriteit. “Het stimuleren van een kwaliteitscultuur vraagt om een brede aanpak.

Exploring the feasibility of whole blood to identify systemic miRNA biomarkers for patients with moderate-to-severe psoriasis

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Evaluation of commercially available ELISA assays as a tool for monitoring and managing pemphigus patients: a prospective study

Background: Pemphigus is a potentially life-threatening auto-immune blistering disease and consequently it is important to monitor disease activity. Objectives: To assess the usefulness of serial antibody titers in the management of pemphigus and to predict disease activity in the clinical follow-up of pemphigus patients. Materials and methods: In this prospective observational study, seven patients with pemphigus vulgaris and three patients with pemphigus foliaceus were examined on a monthly basis for 24 months, or two-weekly during active disease. Disease activity was registered according to a new score system. Results: A total of 158 samples were tested using commercial desmoglein (Dsg) 1 and Dsg3 enzyme-linked immunosorbent assay (ELISA) kits. The 20 U/mL cut-off for the anti-Dsg1 ELISA value was associated with a significantly higher risk of a skin activity score >0 (OR = 7.91, 95% CI = 1.71; 36.65, p = 0.01). A cut-off for disease activity at 5 gave an OR of 11.40 (95% CI = 2.64; 49.09, p = 0.003). Dsg1 values of > 15 had a sensitivity of 79.41% and specificity of 87.80% for predicting a relapse of skin disease in pemphigus patients. For Dsg3, no odds could be calculated for mucosal involvement, nor a predicting value for mucosal relapse. Conclusion: We conclude that only Anti-Dsg1 antibody ELISA values seem valuable in the follow-up of pemphigus patients and carry a predictive value. However, serial antibody titers cannot be seen as absolute indicators of disease activity and we believe that both Dsg1 and Dsg3 ELISA tests should be used with caution to monitor disease activity