Therapeutic drug monitoring in dermatology: the way towards dose optimization of secukinumab in chronic plaque psoriasis.

BACKGROUND: Despite the favourable efficacy profile of secukinumab, clinicians encounter varying clinical responses among patients potentially associated with under- and overdosing. As biologics are expensive, their rational use is crucial and evident. Therapeutic drug monitoring could guide clinicians in making decisions about treatment modifications. AIM: In this multicentre, prospective study, we aimed to develop and validate a secukinumab immunoassay and searched for the therapeutic window in patients with psoriasis. METHODS: We determined secukinumab concentrations at trough in sera from 78 patients with psoriasis at multiple timepoints (Weeks 12, 24, 36, 48 and 52; after Week 52, measurements could be taken at an additional three timepoints) during maintenance phase, using an in-house secukinumab immunoassay consisting of a combination of MA-SEC66A2 as capture antibody and MA-SEC67A9, conjugated to horseradish peroxidase, as detecting antibody. At each hospital visit, disease severity was assessed using the Psoriasis Area and Severity Index (PASI). RESULTS: After quantification, 121 serum samples were included for dose-response analysis. Based on a linear mixed-effects model, secukinumab trough concentrations were found to decrease with increasing body mass index (BMI). Based on receiver operating characteristic (ROC) analysis, we concluded that the minimal effective secukinumab threshold was 39.1 mg/L in steady state, and that this was associated with a 92.7% probability of having an optimal clinical response (PASI ≤ 2 or reduction in PASI of ≥ 90%). CONCLUSIONS: Monitoring and targeting a secukinumab trough concentration of 39.1 mg/L may be a viable treatment option in suboptimal responders. In patients with higher BMI, weight-based dosing may be needed in order to prevent underdosing.

Standardizing serial photography for assessing and monitoring vitiligo: A core set of international recommendations for essential clinical and technical specifications.

BACKGROUND: Clinical photography is an important component of the initial assessment and follow-up of patients with vitiligo in clinical practice and research settings. Standardization of this photographic process is essential to achieve useful, high-quality, and comparable photographs over time. OBJECTIVE: The aim is to develop an international consensus for a core set of recommendations for standardized vitiligo clinical photography. METHODS: Based an international meeting of vitiligo experts, a standard operating procedure was developed for vitiligo photography in daily practice and research settings. This protocol was subsequently reviewed by 20 vitiligo experts until agreement was reached. RESULTS: The resulting protocol includes a set of 10 and 15 photographs for clinical practice and research purposes, respectively. The photographic series are based on anatomic units included in the Vitiligo Extent Score. Furthermore, graphic representations of standardized positioning and suggestions for guidelines to standardize the process (background color, lighting, position marking, scales, materials, instruments) for both color and ultraviolet photographs are described. CONCLUSIONS: This consensus-based protocol for vitiligo photography will harmonize imaging for both clinical practice, translational research, and clinical trials. It can improve outcome assessment, foster multicenter collaboration, and promote better communication with patients regarding outcomes of treatment.

Comparison of Personality Traits among Patients with Psoriasis, Atopic Dermatitis, and Stress: A Pilot Study.

BACKGROUND: Psoriasis and atopic dermatitis are chronic skin diseases that greatly affect the quality of life. Both diseases can be triggered or exacerbated by stress. OBJECTIVE: We aimed to differentiate personality traits between patients with chronic skin conditions and people treated for stress in a pilot study. METHODS: Patients participating voluntarily in educational programs in Belgium and Switzerland were recruited to complete personality trait questionnaires, including the Temperament and Character Inventory (TCI) and the Tridimensional Personality Questionnaire (TPQ). A comparison was made with patients treated for work-related stress. RESULTS: A total of 48 and 91 patients suffering from skin diseases and work-related stress, respectively, were included in the study. Based on the questionnaires, we found that dermatology patients were less persistent and impulsive than those with work-related stress. Dermatology patients also exhibited more rigidness and less focus on performance. Finally, patients with work-related stress seem more likely to change in response to health-promoting programs than patients with chronic dermatoses. CONCLUSION: Patients with chronic skin diseases may perceive and cope with stress differently in comparison to patients with work-related stress due to inherent personality traits. Therefore, stress coping mechanisms may differ among different diseases. More research is needed into the design of educational interventions and the impact of personality traits in disease-specific groups.

Therapeutic patient education and self-management support for patients with psoriasis - a systematic review.

Psoriasis is a chronic inflammatory skin condition. Patient education may be one option to improve adherence and coping. The aim of this systematic review is to identify studies evaluating educational interventions for psoriasis patients. The review was conducted following the methods recommended by Cochrane. We searched seven databases, one trial register and three grey literature repositories. Data screening and extraction was performed independently by two reviewers. Cochrane Risk of Bias 2.0, ROBINS-I, and NIH tools were used. Additionally, the APEASE criteria were applied. We evaluated 16 studies. Two randomized clinical trials (RCTs) evaluated patient-practitioner or patient-nurse one-to-one interventions, one RCT assessed a web-based intervention and three RCTs reported group interventions taking place frequently; one RCT reported one-off group sessions. The remaining RCT compared the healthcare professionals involved. The risk of bias rating ranged from "some concerns" to "high". Three RCTs found an effect. We included four controlled clinical trials (CCTs), one of which had an effect. One of the four before-and-after-studies warrants further investigation. Despite similarities in delivery mode across the interventions, patients who were eligible and settings in which interventions were delivered differed. Interventions that included an individual (one-to-one) session appeared to be successful. Two interventions seem suitable for adaptation using APEASE: the topical treatment program and motivational interviewing after climate therapy.

Towards the development of a RNAi-based topical treatment for psoriasis: Proof-of-concept in a 3D psoriasis skin model.

RNA interference has emerged as a powerful tool for therapeutic gene silencing, as it offers the possibility to silence virtually any known pathology-causing gene. However, in vivo delivery of RNAi molecules is hampered by their unfavourable physicochemical characteristics and susceptibility to degradation by endogenous enzymes. To overcome these limitations, we recently developed an elastic liposomal formulation, called DDC642, as topical delivery system of therapeutic RNAi molecules for skin disorders. In this study, we validated the therapeutic efficacy of DDC642-encapsulated RNAi molecules in the treatment of psoriasis using 3 different in vitro models: a standardized keratinocyte monolayer culture, psoriasis-induced keratinocytes and a psoriasis-reconstructed skin model. Four genes (IL22RA1, KRT17, DEFB4 and TSLP), known to be upregulated in psoriatic lesions, and thereby key players in psoriasis pathogenesis were selected. Moreover, the possibility of using a combined siRNA therapy in the topical treatment of psoriasis was explored. Results indicate a successful gene silencing of each different target, both at mRNA and protein levels. Additionally, siRNA-DDC642 treatment resulted in a reduced expression of specific psoriasis markers, indicating their potential in future therapeutic approach. The examined siRNA combination (ie simultaneous knockdown of KRT17, DEFB4 and TSLP) showed an enhanced reduction in TSLP expression, whereas the decrease in K17 protein expression was impaired in psoriatic keratinocytes. Although the here examined siRNA combination could still be further improved, our study proved already in vitro the clinical potential of targeting multiple genes at once, each playing a different role in a complex disease such as psoriasis.

Dual Inhibition of TNFR1 and IFNAR1 in Imiquimod-Induced Psoriasiform Skin Inflammation in Mice.

Psoriasis is a chronic inflammatory skin disease affecting 2-3% of the world population and is mainly characterized by epidermal hyperplasia, scaling, and erythema. A prominent role for TNF in the pathogenesis of psoriasis has been shown, and consequently various types of TNF antagonists such as etanercept and infliximab have been used successfully. Recently, increasing amounts of data suggest that type I IFNs are also crucial mediators of psoriasis. To investigate whether blocking their respective receptors would be useful, TNFR1- and IFNAR1-deficient mice were challenged with Aldara, which contains imiquimod, and is used as an experimental model to induce psoriasis-like skin lesions in mice. Both transgenic mice showed partial protection toward Aldara-induced inflammation compared with control groups. Additionally, TNFR1 knockout mice showed sustained type I IFN production in response to Aldara. Double knockout mice lacking both receptors showed superior protection to Aldara in comparison with the single knockout mice and displayed reduced levels of IL-12p40, IL-17F, and S100A8, indicating that the TNF and type I IFN pathways contribute significantly to inflammation upon treatment with Aldara. Our findings reveal that dual inhibition of TNFR1 and IFNAR1 may represent a potential novel strategic treatment of psoriasis.

Antisense oligonucleotides against TNFR1 prevent toxicity of TNF/IFNγ treatment in mouse tumor models.

Tumor necrosis factor (TNF) has remarkable antitumor effects, but its systemic therapeutic use is prevented by its lethal inflammatory effects. TNFR1 (P55) is essential for both the antitumor and toxic effects because both of them are absent in P55-deficient mice. In previous work we demonstrated that P55+/- mice are completely resistant to TNF toxicity, while the antitumor effects induced by TNF combined with interferon gamma (IFNγ) remain fully functional in these mice. Hence, a high dose of TNF/IFNγ has an excellent therapeutic potential when P55 levels are reduced, because TNF induces tumor regression without systemic toxicity. Here, we provide proof of principle for therapeutic application of this approach by using antisense oligonucleotides (ASOs). Treatment of mice with ASOs targeting P55 resulted in a strong reduction in P55 protein levels in liver, small intestine and blood mononuclear cells. This P55 downregulation was associated with significant protection of mice against acute TNF toxicity as measured by hypothermia, systemic inflammation and lethality. This treatment also protected mice against toxicity of TNF/IFNγ treatment in several cancer models: B16Bl6, Lewis lung carcinoma and a lung colony model. Our results confirm the therapeutic value of this strategy, which could lead to the development of a safer and more effective TNF/IFNγ antitumor therapy.

Dermatologists on the medical need for therapeutic drug monitoring of biologics in psoriasis: results of a structured survey.

BACKGROUND: Therapeutic drug monitoring (TDM) may lead to more rational use of biologics. Still, TDM is largely underexplored in psoriasis. Little is known about the dosing behavior of biologics by dermatologists, and their attitude toward TDM. OBJECTIVE: Exploration of the awareness and need for the concept of TDM in psoriasis amongst (inter)national dermatologists. METHOD: A survey was distributed at the Belgian Dermatology Days 2019 and Skin Inflammation & Psoriasis International Network (SPIN) Congress 2019. Next, an online survey version was launched amongst the SPIN Scientific Committee members. We collected physician's characteristics, prescription behavior of biologics, data regarding clinical response to biologics and attitude toward TDM. RESULTS: A total of 107 surveys were included for analysis. Most dermatologists were Belgium-based (54.2%), others from European (23.4%) or non-European countries (19.6%). Seventy percent performed either dose increase (64.8%), time interval shortening (74.6%), dose lowering (16.9%) or time interval extension (33.8%). The majority who performed dose adaptations acknowledged the need for TDM. CONCLUSION: This study showed most dermatologists perform dose adaptations empirically. The need for TDM was indicated by the majority, implying the need for effective communication regarding availability, utility and implementation of TDM assays in daily dermatology practice.

Patient-Relevant Outcomes in Psoriasis: A Systematic Review.

Importance: There is a need to define which outcomes matter to patients with psoriasis to deliver value for the patient when managing their condition. Objectives: To generate a comprehensive overview of all outcomes relevant in the management of psoriasis as defined by patients. Evidence Review: A systematic review was performed by searching 3 databases (MEDLINE, Embase, and Web of Science) from August 1, 2019, until March 27, 2021, using a comprehensive search strategy consisting of 4 concepts including psoriasis, patients, outcomes, and relevance. A (citing) reference search was also performed of all retrieved articles. Two independent reviewers screened the retrieved records by title/abstract against the eligibility criteria. Studies were eligible for inclusion if they reported on the importance of outcomes for patients with psoriasis. No language restrictions were used. Data extraction and quality assessment were also performed independently. Quality assessment was done using the QUALSYST tool. Findings: In total, 10 365 records were screened for eligibility, of which 24 studies were included for synthesis. A total of 23 317 patients were evaluated, and 273 (154 unique) items were retrieved. These items were aggregated into 23 outcomes: (almost) complete clearance; symptom control; difficult location clearance; time to clearance; treatment efficacy, sustainability, safety, tolerability, and convenience; comorbidity control; daily and social activity; emotional well-being; intimate relationships; productivity; health-related quality of life; confidence in care; control of disease; communication with care professional; information from other sources than care professional; and cost of care (societal and for the patient). These were then further grouped into 4 core areas: physical/clinical, life impact, resource use, and adverse effects. The mean overall quality of the studies was 75.6% (range, 35.7%-100%). Conclusions and Relevance: This systematic review analyzed patient-relevant outcomes reported in patients with psoriasis to aid in the transition to a value-based treatment approach.

The Effects of Modified Intermittent Fasting in Psoriasis (MANGO): Protocol for a Two-Arm Pilot Randomized Controlled Open Cross-over Study.

BACKGROUND: Psoriasis is a complex disease associated with multiple comorbidities, including metabolic syndrome and leaky gut syndrome. Dietary lifestyle interventions have been reported to affect the disease in terms of lesional severity. It remains unclear how diets affect these comorbidities and the general health in psoriasis patients. Modified intermittent fasting (MIF) on 2 nonconsecutive days has shown beneficial effects on metabolic parameters. A significant advantage of MIF over the currently investigated dietary changes is its feasibility. OBJECTIVE: Here, we aim to study the effects of MIF on skin, gut, and metabolic health in psoriasis patients. METHODS: A 2-arm pilot randomized controlled open cross-over study will be performed in 24 patients with psoriasis. Patients will be randomized 1:1 to either start with 12 weeks of MIF and go on a subsequent regular diet for another 12 weeks or start with 12 weeks of regular diet and do subsequent MIF for 12 weeks. The following parameters will be assessed: demographics, disease phenotype, medical and familial history, psoriasis severity, dermatology-specific and general quality of life, nutritional and physical habits, mental and intestinal health, intestinal and cutaneous integrity, inflammatory and metabolic markers, and satisfaction. RESULTS: A total of 24 participants have been enrolled in the study. The final visit is foreseen for June 2021. CONCLUSIONS: The aim is to uncover the effects of MIF on psoriasis severity and gut health integrity through clinical and molecular investigation. More precisely, we want to map the evolution of the different markers, such as psoriasis severity, permeability, and inflammation, in response to MIF as compared to a regular diet,. Understanding how dietary lifestyles can affect epithelial lineages, such as the skin and gut, will greatly improve our understanding of the development of psoriasis and may offer a nonpharmacological venue for treatments. TRIAL REGISTRATION: ClinicalTrials.gov NCT04418791; https://clinicaltrials.gov/ct2/show/NCT04418791. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/26405.

Promising Tools to Facilitate the Implementation of TDM of Biologics in Clinical Practice.

Therapeutic drug monitoring (TDM) of biologics-encompassing the measurement of (trough) concentrations and anti-drug antibodies-is emerging as a valuable tool for clinical decision making. While this strategy needs further validation, attention on its implementation into the clinic is warranted. Rapid testing and easy sampling are key to its implementation. Here, we aimed to evaluate the feasibility and volunteers' perception of home microsampling for quantification of adalimumab (ADM) concentrations in psoriasis patients. In addition, we compared lateral flow testing (LFT) with enzyme-linked immunosorbent assay (ELISA). Patients participating in the SUPRA-A study (clinicaltrials.gov NCT04028713) were asked to participate in a substudy where volumetric absorptive microsampling (VAMS) was performed at home. At three time points, whole blood and corresponding serum samples were collected for ADM measurement using an in-house ELISA. In addition, the patients' perspective on microsampling was evaluated via a questionnaire. LFT-obtained ADM concentrations agreed very well with ELISA results (Pearson's correlation = 0.95 and R2 = 0.89). ADM concentrations determined in both capillary (via finger prick) and corresponding venous blood VAMS samples correlated strongly with serum concentrations (Pearson's correlation = 0.87). Our preliminary data (n = 7) on rapid testing and home-based microsampling are considered promising with regard to TDM implementation for adalimumab, warranting further research.

Image analysis systems to calculate the surface area of vitiligo lesions: A systematic review of measurement properties.

Several digital image analysis systems have been developed for surface calculation of vitiligo lesions. Critical assessment of their measurement properties is crucial to support evidence-based recommendations on the most suitable instruments and will reveal the need for future research. A systematic review was performed to systematically summarize, compare, and critically assess the measurement properties of digital and analogue analysis systems for surface calculation of vitiligo lesions following the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) recommendations. Nineteen clinical trials were selected including 25 different instruments. Manual tracing on transparent sheets (contact planimetry) combined with digital measurement or point counting can be considered as the best validated method for the evaluation of target lesions taking into account the skin curvatures. Two-dimensional digital imaging analysis on photographs seems also robust although confirmatory data of different research groups using the same digital instrument in a wide range of skin types are missing. Analysis based on 3D photography is still in its early stage but is promising for whole-body analysis. However, the reported data on the quality of the instruments for surface area calculation of vitiligo lesions were in general rather limited. Therefore, future high-quality validation studies are required also including full body evaluations.

Gut-Skin Axis: Current Knowledge of the Interrelationship between Microbial Dysbiosis and Skin Conditions.

The microbiome plays an important role in a wide variety of skin disorders. Not only is the skin microbiome altered, but also surprisingly many skin diseases are accompanied by an altered gut microbiome. The microbiome is a key regulator for the immune system, as it aims to maintain homeostasis by communicating with tissues and organs in a bidirectional manner. Hence, dysbiosis in the skin and/or gut microbiome is associated with an altered immune response, promoting the development of skin diseases, such as atopic dermatitis, psoriasis, acne vulgaris, dandruff, and even skin cancer. Here, we focus on the associations between the microbiome, diet, metabolites, and immune responses in skin pathologies. This review describes an exhaustive list of common skin conditions with associated dysbiosis in the skin microbiome as well as the current body of evidence on gut microbiome dysbiosis, dietary links, and their interplay with skin conditions. An enhanced understanding of the local skin and gut microbiome including the underlying mechanisms is necessary to shed light on the microbial involvement in human skin diseases and to develop new therapeutic approaches.

The implementation of a structured specialized consultation for psoriasis management.

Objectives: Psoriasis is a chronic skin disease requiring a multidimensional approach, given its varying appearance, presence of comorbidities and complex treatment regimens. Psoriasis care is however often performed fragmented and, in case of flares, reactive with little integrated information on and for the patient. Literature suggests a multileveled approach of psoriasis, but the effects of its implementation have not yet been validated. The aim of this study is to analyze the impact of a multileveled psoriasis consultation format, named PsoPlus, which has been implemented since 2012 in the Department of Dermatology at Ghent University Hospital in Belgium.Methods: The patient population was divided into two groups: one following the regular consultation and one following the PsoPlus format. Demographic data, clinical outcome and treatment approach of psoriasis patients were compared.Results: Patients who opted for the specialized PsoPlus consultation were younger and had longer disease duration. Decision parameters such as disease severity and quality of life were reported more often in the PsoPlus group. In the latter, a higher rate of patients were started on systemic therapy compared to the regular consultation group, and reporting on adverse events was done more frequently.Conclusion: The implementation of a specialized consultation with comprehensive guidance facilitates documentation on disease-relevant parameters such as disease severity and quality of life. This format can be seen as a guidance for capturing data in a structured manner, with evidence showing that it significantly impacts treatment decision, treating not only psoriasis but the patient as a whole.

Dose reduction of the new generation biologics (IL-17 and IL-23 inhibitors) in psoriasis: study protocol for an international, pragmatic, multicenter, randomized, controlled, non-inferiority study-the BeNeBio study.

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory skin disease for which biologics are effective treatments. Dose reduction (DR) of the first generation biologics seems a promising way for more efficient use of expensive biologics. A substantial part of patients on tumor necrosis factor (TNF)-alfa inhibitors and ustekinumab could successfully lower their dose, after following a tightly controlled DR strategy. The objective of this study is to assess whether controlled DR of interleukin (IL)-17 and IL-23 inhibitors in psoriasis patients with low disease activity is non-inferior (NI) to usual care (UC). METHODS: This is an international, prospective, multicenter, pragmatic, randomized, non-inferiority trial. A total of 244 patients with stable low disease activity (Psoriasis Area and Severity Index (PASI) ≤ 5) for at least 6 months and using secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab, or tildrakizumab in the standard dose, together with stable low disease activity, defined as a PASI ≤ 5 and Dermatology Life Quality Index (DLQI) ≤ 5 at the moment of inclusion, will be randomized 2:1 to DR or UC. In the DR group, dosing intervals will be prolonged stepwise to achieve 66% and 50% of the original dose. Disease activity is monitored every 3 months by PASI and DLQI. In case of disease flare (i.e., PASI and/or DLQI increase), treatment is adjusted to the previous effective dose. The primary outcome is the incidence proportion of persistent flares (PASI > 5 for ≥ 3 months), which will be compared between arms. Secondary outcomes include proportion of patients with successful DR, (course of) PASI and DLQI, serious adverse events (SAEs), health-related quality of life, costs, and pharmacokinetic profile. Outcomes of DR will be compared to UC. DISCUSSION: With this study, we aim to assess whether DR of IL-17 and IL-23 inhibiting biologics can be achieved for psoriasis patients with low disease activity, without losing disease control. Reducing the dose may lead to more efficient use of biologics. TRIAL REGISTRATION: ClinicalTrials.gov NCT04340076 . Registered on April 9 2020.

Development and validation of immunoassays for monitoring of guselkumab and anti-guselkumab antibodies in patients with moderate-to-severe psoriasis.

Therapeutic drug monitoring, which is the measurement of drug concentrations in the blood, is a useful tool to guide clinical decision-making and treatment adjustments, on the condition that drug concentrations are correlated with treatment response. For guselkumab, an anti-IL-23 monoclonal antibody for the treatment of moderate-to-severe psoriasis, such a concentration-response relationship could not yet be determined as no commercial assays for the quantification of this drug or antibodies against this drug are available. Therefore, the aim of this study was to develop and validate immunoassays for the quantification of guselkumab and anti-guselkumab antibodies according to the guidelines of the European Medicines Agency (EMA). A diverse panel of 20 highly specific anti-guselkumab monoclonal antibodies (MA-GUS) was generated of which eight revealed a neutralizing capacity of ≥65 %. At least seven different antibody clusters were identified based on their epitope binning profile. Using MA-GUS9F6 as the capture antibody and MA-GUS12G12 as the detection antibody, an ELISA was developed with a dose-response curve ranging from 0.08 to 5 ng/mL. The assay was specific, selective and could accurately and precisely quantify guselkumab concentrations in spiked healthy control serum and serum from guselkumab-treated psoriasis patients with a cut-off for quantification of 0.014 µg/mL. The presence of IL-23 in physiological concentrations or of non-neutralizing antibodies did not impact the quantification of guselkumab, while the presence of neutralizing antibodies did. Using MA-GUS12A9 as a calibrator, two anti-guselkumab antibody assays were developed to detect anti-guselkumab antibodies, which differ in the threshold for detection and quantification and the tolerance to the presence of guselkumab. Together, these validated immunoassays are essential to establish a concentration-response relationship and will allow the future implementation of therapeutic drug monitoring in moderate-to-severe psoriasis patients receiving guselkumab treatment.

Improving Patient Involvement in the Lifecycle of Medicines: Insights From the EUPATI BE Survey.

EUPATI Belgium (EUPATI.be) is an informal gathering of local partners who are interested in improving patient involvement in healthcare innovation and medicines research and development. EUPATI.be brings together various stakeholders from different areas related to healthcare including patients, academia and industry. In doing so, we create an innovative collaborative approach where actors from different backgrounds work toward improving patient involvement in medical research, and putting the patient at the center of the Belgian healthcare system. Previously, we performed in-depth interviews with a small group of stakeholders on patient involvement. Here, we elaborate on our previous findings by using a nation-wide survey to inquire into Belgian stakeholders' perception on patient involvement. To this end, an electronic survey was available in French, Dutch and English, and accessible for 11 months. Twelve questions were asked, including 11 multiple choice questions and 1 open question. The latter was thematically analyzed according to the framework method. A total of 117 responses were registered and descriptive statistics were performed. The majority of respondents could be categorized into patient, academia and industry, whereas policy makers, payers, and healthcare professionals were underrepresented. We identified several barriers that hamper patient involvement, which were sometimes more reported by specific stakeholder groups. Next, we found that various stakeholders still consider patient involvement as a passive role, i.e., medical subject in a clinical trial. Respondents also reported that the role of the various stakeholders needed more clarification; this was also confirmed by the level of trust amongst the various stakeholders. Existing and the wish for more collaboration with the various stakeholders was reported by almost all respondents. Based on this survey, we can define the potential of involving patients in the medical research and development in the Belgian landscape. Our results will help to understand and tackle the various barriers that currently hamper patient involvement, whilst highlighting the need for a collaborative landscape from the multi-stakeholder perspective.

Validation of a physician global assessment tool for vitiligo extent: Results of an international vitiligo expert meeting.

Currently, vitiligo lacks a validated Physician Global Assessment (PGA) for disease extent. This PGA can be used to stratify and interpret the numeric scores obtained by the Vitiligo Extent Score (VES). We investigated the interrater reliability of a 5-point PGA scale during an international vitiligo workshop. Vitiligo experts from five different continents rated photographs of non-segmental vitiligo patients with varying degrees of extent with the PGA score. Good interrater agreements (intraclass correlation coefficient >0.6) were observed between the raters overall and within each continent. All hypotheses to evaluate construct validity were confirmed. Median VES values per category were for limited 1.10 [IQR: 0.21-1.67], moderate 3.17 [IQR: 1.75-6.21], extensive 9.58 [IQR: 6.21-13.03] and very extensive 42.67 [IQR: 21.20-42.67]. Defined categories for vitiligo extent can be valuable for inclusion criteria and may impact future reimbursement criteria.