Psoriasis is an immune-mediated inflammatory disorder, where the majority of the patients suffer from psoriasis capitis or scalp psoriasis. Current therapeutics remain ineffective to treat scalp lesions. In this study, we present a whole-metagenome characterization of the scalp microbiome in psoriasis capitis. We investigated how changes in the homeostatic cutaneous microbiome correlate with the condition and identified metagenomic biomarkers (taxonomic, functional, virulence factors, antimicrobial resistance genes) that could partly explain its emergence. Within this study, 83 top and back scalp samples from healthy individuals and 64 lesional and nonlesional scalp samples from subjects with untreated psoriasis capitis were analyzed. Using qPCR targeting the 16S and 18S ribosomal RNA genes, we found a significant decrease in microbial load within scalp regions affected by psoriasis compared with that in their nonlesional counterparts. Metagenomic analysis revealed that psoriatic lesions displayed significant lower Cutibacterium species (including C. modestum, C. namnetense, C. granulosum, C. porci), along with an elevation in Staphylococcus aureus. A heightened relative presence of efflux pump protein-encoding genes was detected, suggesting potential antimicrobial resistance mechanisms. These mechanisms are known to specifically target human antimicrobial peptides (including cathelicidin LL-37), which are frequently encountered within psoriasis lesions. These shifts in microbial community dynamics may contribute to psoriasis disease pathogenesis.

Introduction: Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, is approved in the US, EU, and other countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib was effective and well tolerated in the global, 52-week, phase 3 POETYK PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751) trials. Here, efficacy of deucravacitinib in scalp psoriasis was evaluated by baseline severity of psoriasis in the trial patients with scalp involvement. Methods: Patients with moderate to severe scalp involvement (scalp-specific Physician Global Assessment [ss-PGA] ≥3) at baseline were included in this analysis. Efficacy outcomes (ss-PGA 0/1 and Psoriasis Scalp Severity Index [PSSI] 90) were reported through Week 24 (pooled PSO-1/PSO-2, before PSO-2 rerandomization, n=514) and Week 52 (PSO-1, continuous deucravacitinib treatment, n=192). Outcomes were stratified by baseline PASI score 12-<15 (low) or ≥15 (high) and baseline BSA involvement 10%-≤15% (low) or >15% (high). Results: ss-PGA 0/1 response rates were high and slightly greater in the high versus low PASI subgroup at Week 24 (65.8% and 58.3%, respectively) and Week 52 (73.5% and 60.0%). Similarly, PSSI 90 response rates were high and also somewhat greater in the high versus low PASI subgroup at Week 24 (55.3% and 45.8%) and Week 52 (66.0% and 53.3%). Across the 2 baseline BSA subgroups, ss-PGA 0/1 and PSSI 90 response rates were comparable at Weeks 24 and 52. Conclusion: Deucravacitinib treatment was effective in patients with scalp involvement in psoriasis regardless of overall baseline disease severity.

Chronic pruritus (CP) is frequent in general medicine and the most common complaint in general dermatology. The prevalence of CP is expected to rise in the future due to the ageing population. The clinical presentation, underlying aetiology and treatment strategy of CP are heterogeneous. Also, individual treatment aims and physical, psychic and economic burdens of patients might vary. Chronic prurigo (CPG) is the most severe disease in the chronic pruritus spectrum, being associated with long-standing scratch-induced skin lesions and a therapy refractory itch-scratch-cycle. It is thus important to raise disease awareness for CP and CPG in the general public and among decision-makers in the health system. Further, there is a need to support a rational clinical framework to optimize both diagnostics and therapeutics. Currently, there is still a shortcoming regarding approved therapies and understanding CP/CPG as severe medical conditions. Therefore, the EADV Task Force Pruritus decided to publish this white paper based on several consensus meetings. The group consented on the following goals: (a) ensure that CP is recognized as a serious condition, (b) increase public awareness and understanding of CP and CPG as chronic and burdensome diseases that can greatly affect a person's quality of life, (c) clarify that in most cases CP and CPG are non-communicable and not caused by a psychiatric disease, (d) improve the support and treatment given to patients with CP to help them manage their disease and (e) publicize existing therapies including current guidelines. We aim to point to necessary improvements in access and quality of care directed to decision-makers in health policy, among payers and administrations as well as in practical care.

Abstract Background In the Belgian DISCOVER study, conducted in 2011–2012 before the advent of the IL‐17 and IL‐23 Inhibitors, significant undertreatment of patients with plaque psoriasis was reported. Objectives The present study aimed to re‐evaluate the real‐world clinical management and quality of care of moderate‐to‐severe plaque psoriasis patients treated with systemic treatment for at least 24 weeks in clinical practice in Belgium. Methods This cross‐sectional and retrospective chart review (REDISCOVER) was conducted in 2021–2022 in private practices and hospitals in Belgium. Patient data were collected during one single visit and included assessments of psoriasis severity (Psoriasis Area Severity Index [PASI], Body Surface Area [BSA], Pruritus VAS scale) and Health‐Related Quality of Life (Dermatology Life Quality Index [DLQI]) and other selected criteria of the Belgian treat‐to‐target (T2T) outcome set. Results Of the 306 patients included in the study, 81.4% received treatment with biologicals and 18.6% with traditional systemics, that is, methotrexate or apremilast. IL‐23 Inhibitors (33.7%) and methotrexate (10.8%) were the most prescribed biologicals and traditional systemic, respectively. Between the time of treatment initiation and enrolment, the average PASI and BSA scores decreased, indicating treatment benefits. PASI scores were lower in patients treated with biologicals versus patients treated with traditional systemics. Full achievement of the two Belgian T2T guidelines dimensions was observed in 51% of the patients. Nonetheless, patients were generally satisfied with their treatment (96.1%) and physicians evaluated the treatment as adequate for most patients (87.3%). Conclusions Compared to 10 years ago, a demonstrable improvement in care of moderate‐to‐severe psoriasis patients was observed in Belgium. This was reflected by substantial achievement of the current treatment goals and high treatment satisfaction by both patients and physicians. While one out of five patients is not achieving targeted goals, and is not treated with a biological, it seems there is still room for improvement.

Although warmth is a key sign of inflammatory skin lesions, an objective assessment and follow-up of the temperature changes are rarely done in dermatology. The recent availability of accurate, sensitive and cost-effective thermography devices has made the implementation of thermography in clinical settings feasible. The aim of this scoping review is to summarize the evidence around the value and pitfalls of infrared thermography (IRT) when used in the dermatology clinic. A systematic literature search was done for original articles using IRT in skin disorders. The results concerning the potential of IRT for diagnosis, severity staging and monitoring of skin diseases were collected. The data on the sensitivity and specificity of IRT were extracted. Numerous studies have investigated IRT in various skin diseases, revealing its significant value in wound management, skin infections (e.g. cellulitis), vascular abnormalities and deep skin inflammation (e.g. hidradenitis suppurativa). For other dermatological applications such as the interpretation of intradermal and patch allergy testing, hyper-/anhidrosis, erythromelalgia, cold urticaria and lymph node metastases more complex calculations, provocation tests or active cooling procedures are required. Dermatologists should be aware of a learning curve of IRT and recognize factors contributing to false positive and false negative results. Nonetheless, enough evidence is available to recommend IRT as a supplement to the clinical evaluation for the diagnosis, severity and follow-up of several skin diseases.

Introduction: As the COVID-19 pandemic becomes an endemic state, still many questions remain regarding the risks and impact of SARS-CoV-2 infection and vaccination in patients with immune-mediated inflammatory diseases (IMIDs) who were excluded from the phase 3 COVID-19 vaccination trials. Methods: The BELCOMID study collected patient data and serological samples from a large, multicentric IMID patient cohort that was prospectively followed during sequential stages of the pandemic. Patients were stratified according to vaccination status into five groups across three sampling periods. Interactions between SARS-CoV-2 infection, COVID-19 vaccination status, IMID-treatment modalities and IMID course were explored. Results: In total, 2165 patients with IBD, a dermatological or rheumatological IMID participated. SARS-CoV-2 infection rates increased over the course of the pandemic and were highest in IMID patients that had refused every vaccine. After baseline COVID-19 vaccination, serologic spike (S)-antibody responses were attenuated by particular types of immune-modulating treatment: anti-TNF, rituximab, JAKi, systemic steroids, combined biologic/immunomodulator treatment. Nonetheless, S-antibody concentration increased progressively in patients who received a booster vaccination, reaching 100% seroconversion rate in patients who had received two booster vaccines. Previous SARS-CoV-2 infection was found as a predictor of higher S-antibody response. Patients who had refused every vaccine showed the lowest rates of S-seroconversion (53.8%). Multiple logistic regression did not identify previous SARS-CoV-2 infection as a risk factor for IMID flare-up. Furthermore, no increased risk of IMID flare-up was found with booster vaccination. Conclusions: Altogether, the BELCOMID study provides evidence for the efficacy and safety of COVID-19 vaccination and confirms the importance of repeated booster vaccination in IMID patients.

Abstract Metabolic mediators play an important role in regulating inflammation(1). Rheumatoid arthritis and spondyloarthritis are common inflammatory diseases of the joint, aggravated in context of obesity(2). These patients experience systemic bone loss(3,4), which is not sufficiently controlled by disease-modifying therapeutics, despite adequate control of inflammation(5,6). Here we report an unexpected role for GDF15 (Growth Differentiation Factor 15), a central mediator of food intake(7–10), in inflammation-associated bone loss. Serum GDF15 levels were found to be elevated in arthritis patients and inversely correlated with bone density. However, GDF15 itself does not appear to promote arthritis. Rather, GDF15 mediates trabecular bone loss through its receptor GFRAL, which is expressed exclusively in the hindbrain(7–10). GDF15-GFRAL binding results in β-adrenergic activation of bone Marrow Adipogenic Lineage Precursors (MALPs), mesenchymal cells which are known to stimulate osteoclasts and trigger bone loss(11–14). These data demonstrate how a metabolic mediator controls bone loss through a brain-bone axis in inflammatory diseases. These findings may lead to more specific therapeutic interventions to protect bone through targeting GDF15 or MALPs.

Background: Infliximab, an anti–tumor necrosis factor monoclonal antibody, has revolutionized the pharmacological management of immune-mediated inflammatory diseases (IMIDs). This position statement critically reviews and examines existing data on therapeutic drug monitoring (TDM) of infliximab in patients with IMIDs. It provides a practical guide on implementing TDM in current clinical practices and outlines priority areas for future research. Methods: The endorsing TDM of Biologics and Pharmacometrics Committees of the International Association of TDM and Clinical Toxicology collaborated to create this position statement. Results: Accumulating data support the evidence for TDM of infliximab in the treatment of inflammatory bowel diseases, with limited investigation in other IMIDs. A universal approach to TDM may not fully realize the benefits of improving therapeutic outcomes. Patients at risk for increased infliximab clearance, particularly with a proactive strategy, stand to gain the most from TDM. Personalized exposure targets based on therapeutic goals, patient phenotype, and infliximab administration route are recommended. Rapid assays and home sampling strategies offer flexibility for point-of-care TDM. Ongoing studies on model-informed precision dosing in inflammatory bowel disease will help assess the additional value of precision dosing software tools. Patient education and empowerment, and electronic health record–integrated TDM solutions will facilitate routine TDM implementation. Although optimization of therapeutic effectiveness is a primary focus, the cost-reducing potential of TDM also merits consideration. Conclusions: Successful implementation of TDM for infliximab necessitates interdisciplinary collaboration among clinicians, hospital pharmacists, and (quantitative) clinical pharmacologists to ensure an efficient research trajectory.

Immune-mediated inflammatory diseases with skin manifestations (skIMIDs) may affect multiple organs. Interdisciplinary care (IC) can overcome the fragmented knowledge used in the management of skIMIDs. In skIMIDs-care, patient and healthcare practitioner (HCP) satisfaction with IC is unknown. Yet, patient experience influences adherence and medical outcomes. Moreover, HCP experience influences professional satisfaction, perception of care quality and autonomy. Thus, measuring patient and HCP experience can identify areas for improvement in care delivery. The aim of this scoping review was to gather evidence on patient- and HCP perceptions on skIMID-IC and their measurement. We systematically searched on 30 August 2023 PubMed/EMBASE/Cinahl/Web of Science. Eligible studies had to address explicitly experience of IC by patients or HCPs. A conceptional synthesis appraised how experiences were measured and IC was perceived by patients and HCPs. The database search resulted in 21 eligible studies. Fourteen described positive patient and HCP experiences with a specific IC programme. These studies were heterogenous on the levels of IC models, medical conditions, measurement methods and outcomes. Despite that patients and HCPs rated such tailored IC models positively, seven studies on a geographically broader region reported less satisfaction with IC. A conceptual analysis identified domains deemed as important regarding IC: 'general satisfaction', 'patient-HCP interaction', 'information', 'functioning of IC', 'benefits of IC'. For patients, 'access to care' and 'disease management' were added. For HCPs 'illness perception' was deemed relevant. The heterogeneous way in how IC experience is captured hinders strong conclusions, which mandates the development of standardized analysis tools. Experience with IC in skIMIDs strongly depends on the context of the provided IC and patient experience seems to be better in local IC programmes than systems rolled out in larger geographical regions. Future need is to develop a core IC outcome set including medical outcomes, process indicators, financial indicators, plus patient and HCP care experience measures.

Previously, we showed that the combination of methotrexate and adalimumab treatment leads to less antidrug antibody development. In this study, we quantify the pharmacokinetics/pharmacodynamics (PK/PD) of adalimumab and evaluate the influence of methotrexate cotreatment. A population PK-PD model was developed using prospective data from 59 patients with psoriasis (baseline PASI = 12.6) receiving adalimumab over 49 weeks. Typical PK and PD parameters and their corresponding interpatient variability were estimated. We performed a covariate analysis to assess whether interpatient variability could be explained by addition of methotrexate and other covariates. In total, 330 PASIs, 252 adalimumab serum concentrations, and 247 antidrug antibody titers were available. Presence of antidrug antibodies (adalimumab group = 46.7%, adalimumab + methotrexate group = 38.7%; P = .031) was correlated with increased adalimumab apparent clearance (P < .001). In the PD model, the use of concomitant methotrexate was borderline to significantly correlated with a decreased half-maximal inhibitory concentration (adalimumab concentration for which clinical response score is reduced by half; P < .10). On the basis of our PK-PD model, concomitant use of methotrexate indirectly increases adalimumab concentration, partially through less antidrug antibodies formation, which may result in better efficacy.

Abstract Background Biologics for psoriasis demonstrate varying clinical outcome in real‐world practice, implying potential under‐ and overexposure. Objectives In this prospective cohort study we aimed to develop and validate an in‐house sandwich‐type enzyme‐linked immunosorbent assay (ELISA) for ixekizumab (IXE), and to explore whether there is an exposure‐response relationship in standard maintenance dose for IXE, and whether patient factors influence IXE exposure and clinical outcome. Methods This was a prospective, multicentric, cohort study in psoriasis patients treated with IXE according to standard dosing regimen (BIOLOPTIM‐IXE). IXE trough concentrations (TCs) in sera collected at multiple timepoints were measured using an in‐house immunoassay. Results Using MA‐IXE117E12 and MA‐IXE100F5‐biotin as the capture and detection antibodies, respectively, an ELISA was developed with an exposure‐response curve ranging from 10 to 0.16525 ng/mL. One hundred‐fifteen steady‐state serum samples from 48 patients (17 [35.4%] bio‐experienced; median body weight, 81.5 kg) were measured. Optimal responders (Psoriasis Area and Severity Index [PASI] ≤ 2) had significantly higher TCs than suboptimal responders (PASI > 2) (median TCs, 4.4 and 3.0 μg/mL, respectively; p = 0.026). Median cohort IXE TC was 4.1 µg/mL [2.8−6.1]. An optimal steady‐state IXE TC of 3.4 µg/mL was identified for clinical outcome defined by absolute PASI. Median TCs and absolute PASI were significantly lower and worse, respectively, in patients ≥ 90 kg (p < 0.001 and p = 0.013, respectively) and in bio‐experienced subjects (p < 0.001 and p = 0.029, respectively). Conclusions This study identified an IXE exposure‐response relationship and an optimal effective steady‐state TC of 3.4 µg/mL in real‐world psoriasis patients, revealing the potential of therapeutic drug monitoring in optimising IXE use.

Background: Scalp involvement in plaque psoriasis is challenging to treat. Objective: To evaluate the efficacy and safety of deucravacitinib (DEUC) in scalp psoriasis. Methods: POETYK PSO-1 and PSO-2 were global phase 3, 52 -week, double -blinded trials in adults with moderate to severe psoriasis. Patients were randomized 1:2:1 to oral placebo, DEUC 6 mg once daily, or apremilast 30 mg twice daily. This pooled secondary analysis evaluated scalp -specific Physician Global Assessment score of 0 or 1 (0/1), >= 90% improvement from baseline in Psoriasis Scalp Severity Index, and change from baseline in Psoriasis Scalp Severity Index. Adverse events were evaluated through week 16. Results: Overall, 1084 patients with moderate to severe scalp psoriasis at baseline were included. At week 16, response rates were greater with DEUC versus placebo or apremilast for scalp -specific Physician Global Assessment 0/1 (64.0% vs 17.3% vs 37.7%; P < .0001), >= 90% improvement from baseline in Psoriasis Scalp Severity Index (50.6% vs 10.5% vs 26.1%; P < .0001), and change from baseline in Psoriasis Scalp Severity Index. Responses were maintained through 52 weeks with continuous DEUC. Safety was consistent with the entire study population. Limitations: Lack of data in milder scalp psoriasis. Conclusion: DEUC was significantly more efficacious than placebo or apremilast in improving moderate to severe scalp psoriasis and was well tolerated.

Background: Value-based healthcare (VBHC) is an increasingly employed strategy to transform healthcare organizations into economically sustainable systems that deliver high-value care. In dermatology, the need for VBHC is evident as chronic skin diseases require long-term, often expensive treatments. This narrative review aims to introduce dermatologists to the principles and implementation of VBHC. Summary: VBHC emphasizes maximizing outcomes that are directly relevant to patients. Key components of VBHC include a systematic assessment of standardized patient-relevant outcomes by using core outcome sets and measurement of healthcare cost for the individual patient. Systematic reporting and comparing of risk-adjusted outcomes across the full cycle of care for a specific condition provide benchmarked feedback and actionable insights to promote high-value care and reduce low-value care. VBHC aims to organize care around the patient in condition-specific and team-based integrated practice units with multidisciplinary collaboration, utilize information technology platforms to enable digital data monitoring, reduce cost, and eventually reform payment systems to support bundled payments for the overall care cycle. VBHC implementation in practice necessitates the establishment of a systematic framework for outcome-based quality improvement, the incorporation of value and outcomes in shared decision-making practices, and the cultivation of a value-centric culture among healthcare professionals through continuous training. Key Messages: Dermatologists can benefit from implementing VBHC principles in their practice. An essential step toward value-driven dermatological care is to start measuring outcomes relevant for patients for each patient, which is lacking partly due to the absence of core outcome sets developed for clinical practice. By reducing low-value care and emphasizing optimal patient-centered outcomes, VBHC has the potential to improve the quality of care and ensure cost containment. Efforts are needed to enhance the development and uptake of VBHC in dermatological clinical practice to realize these benefits.

In recent years, there have been significant breakthroughs in the identification of immunological components of skin diseases and in the development of immunomodulatory drugs. Novel therapies create exciting prospects for personalized care. This article provides an overview of the role played by Th1, Th2, Th17, and follicular Th pathways in the most common skin diseases. Additionally, it elucidates the impact of current and upcoming treatments on each of these signaling cascades. Skin diseases predominantly influenced by a single dominant Th pathway such as psoriasis and atopic dermatitis are well-suited for biologics. However, in many other disorders a complex interplay between different immune pathways exists. This can lead to inconsistent efficacy of biologics based on individual patient profiles. In case of activation of several Th pathways, it may be more suitable to consider conventional therapies or JAK inhibitors. Increasing immunological insights have transitioned from laboratory research to practical applications, a trend that is expected to continue growing in the future.

Psoriasis is a chronic immune-mediated skin disease with several comorbidities and a considerable influence on quality of life. Many patients with moderate-to-severe psoriasis are undertreated and have a substantial disease duration before effective treatment is started. This study analyzed patient and disease characteristics and time to effective treatment of patients with psoriasis who consulted PsoPlus. It also examined whether a treat-to-target (T2T) approach, which is implemented in PsoPlus, has an impact on treatment choice and disease progression. Through a single center, retrospective study, 170 patients in the PsoPlus dedicated clinic were compared at moment of enrollment in PsoPlus and at the last recorded consultation in 2021. Median disease duration at the first PsoPlus consultation was 16.0 (interquartile range (IQR) 19.0) years. There was a significant difference in Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) between the first and the last recorded PsoPlus consultation (PASI 6.0 (IQR 6.4) vs. 0.6 (IQR 2.6); DLQI 11 (IQR 11) vs. 2 (IQR 6); p < 0.001). A weak positive Spearman correlation (rs) was found between disease duration and PASI at the first PsoPlus consultation (rs = 0.175; p = 0.034), while a weak negative correlation (rs = − 0.2; p = 0.013) was found at the last registered PsoPlus consultation. Patients with a disease duration of more than 20 years had significantly more switches of treatment than those with a shorter disease duration (p < 0.001). Median time from psoriasis onset until PASI ≤ 2 was 16.0 years. Median time from the first PsoPlus consultation until PASI ≤ 2 was 7.0 months. The PsoPlus program with its T2T approach effectively improves clinical outcomes and quality of life for patients with psoriasis in a relatively short period, emphasizing the value of a structured, personalized treatment plan for long-term management.

Introduction: Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, is approved in the US, EU, and other countries for treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib was effective and well-tolerated in the global, 52-week, phase 3 POETYK PSO-1 (NCT03624127) and PSO-2 (NCT03611751) trials. Here, efficacy of deucravacitinib in scalp psoriasis was evaluated by baseline severity of psoriasis in the trial patients with scalp involvement.

Background: Response to biologics in psoriasis varies in real-world settings. Serum biomarkers could aid biologic selection and dose modifications to improve patient outcomes while encouraging cost-effective care. Objectives: To explore the exposure-response relationship for guselkumab (GUS), to define a GUS concentration target for optimal response and to evaluate the potential of serum protein levels as predictive biomarker candidates. Methods: This is a prospective, multicentric, cohort study in psoriasis patients treated with GUS. Serum GUS trough concentrations (TCs) collected at multiple timepoints were measured using an in-house immunoassay. Next, proximity extension assay technology (Target 96 Inflammation Panel Olink (R)) was used to measure serum protein levels in a subcohort including 38 GUS patients (week 0 and week 4), six psoriasis patients naive for systemic treatment and four healthy controls. Results: Seventy-five patients participated and 400 samples were collected. Guselkumab TCs and clinical response were correlated at week 4, week 12 and in steady-state (>= 20 weeks). Optimal responders (Psoriasis Area and Severity Index [PASI] <= 2) had significantly higher TCs than suboptimal responders from week 4 onwards in treatment. An optimal steady-state TC of 1.6 mu g/mL was defined. Although TC and absolute PASI were lower and worse, respectively, in patients weighing >= 90 kg, clinical outcomes referred to desirable to excellent PASI ranges. Therefore, we do not recommend systematically higher GUS doses in obese patients. We could not reveal early differentially expressed proteins to distinguish future optimal from suboptimal responders. Conclusions: We demonstrated an exposure-response relationship for GUS and an optimal steady-state TC of 1.6 mu g/mL in real-world psoriasis patients. Hereby, we deliver more evidence that therapeutic drug monitoring poses a promising strategy in optimizing GUS treatment. No biomarker candidates were identified through serum proteomics. We propose protein screening should be repeated in larger cohorts to continue the quest for predictive biomarkers.