A Prospective, Monocentric Case-Control Study on Uncontrolled Psoriasis as Independent Risk Factor for a Hypercoagulable State.

INTRODUCTION: Chronic inflammatory diseases, including psoriasis, are associated with development of venous thromboembolism (VTE). The clot lysis profile (CLP) provides information on both the clotting tendency and fibrinolysis activity. We hypothesized that CLP in uncontrolled psoriasis patients is disturbed towards more clotting/less lysis compared to healthy controls (HC) and that successful psoriasis treatment could normalize the CLP. In this project, we aim to compare the CLP in patients with uncontrolled psoriasis with age- and sex-matched HC and investigate the effect of anti-inflammatory treatment on CLP. METHODS: Patients with uncontrolled psoriasis [psoriasis area severity index (PASI) or body surface area (BSA) > 10] (n = 87) and HC (n = 87) were recruited at a tertiary dermatology department. Samples from patients were obtained before treatment and when disease control was obtained (PASI < 3). Amplitude, area under the curve (AUC) and 50% clot lysis time were determined. RESULTS: At baseline, psoriasis patients had higher median amplitude and AUC compared with HC (p < 0.0001). After correction for possible confounders (BMI, smoking behavior, psoriatic arthritis, arterial hypertension, diabetes and coronary artery disease), the increased amplitude in psoriasis patients compared to HC remained significant. Successful anti-inflammatory treatment resulted in a significant decrease in amplitude (p = 0.0365). CONCLUSION: This is the first prospective study comparing the CLP of psoriasis patients with that of HC. A significant increase in both amplitude and area under the curve, indicative of a hypercoagulable CLP, was observed in psoriasis patients compared to HC. After successful anti-inflammatory treatment, amplitude significantly decreased.

Identifying risk factors of anti-TNF induced skin lesions and other adverse events in paediatric patients with inflammatory bowel disease.

OBJECTIVES: While higher infliximab (IFX) trough concentrations (TCs) are associated with better outcomes in patients with inflammatory bowel disease (IBD), they could pose a risk for adverse events (AEs), including IFX-induced skin lesions. Therefore, we studied correlations between IFX TCs and occurrence of AEs in paediatric IBD patients. METHODS: In this single-centre study, all children with Crohn's disease (CD) and ulcerative colitis (UC) receiving IFX maintenance therapy who underwent proactive drug monitoring between March 2015 and August 2022 were included. IFX doses/intervals/TCs and patient characteristics were systematically registered, as well as AEs and skin lesions appearance. RESULTS: A total of 109 patients (72 CD and 37 UC) contributed 2913 IFX TCs. During a median follow-up of 3.0 [1.5-4.5] years, we observed 684 AEs in 101 patients and 49 skin lesions in 35 patients. There was no significant difference (p = .467) in median TCs between patients with and without skin lesions. However, higher median IFX doses were associated with an increased hazard rate of skin lesions [HR 1.084 (1.024-1.148), p = .005], in addition to female sex [2.210 (1.187-5.310), p = .016] and diagnosis of CD [1.695 (1.241-1.877), p = .011]. Considering IFX therapeutic TC cut-offs of 5.0 and 9.0 µg/mL, there was no significant difference in AE rate (p = .749 and p = .833, respectively). Also, no significant association between IFX doses and AE rate (p = .159). CONCLUSIONS: Increasing the IFX dose to achieve therapeutic TCs may not increase the overall risk of AEs in paediatric IBD patients. However, concerns arise regarding the risk of skin lesions, especially in female CD patients.

Gender perspective in psoriasis: a scoping review and proposal of strategies for improved clinical practice by European dermatologists.

Background: The prevalence of psoriasis is similar between men and women; however, evidence exists of sex- and gender-related differences in disease expression, impact, coping, and needs of patients with psoriasis. These differences are essential and should be considered in clinical practice and research. Objective: To compile available evidence on sex- and gender-related differences in psoriasis, identify the most critical gaps in clinical practice and research, and use it to propose strategies for improved clinical practice. Methods: Six European dermatologists selected the topics to consider according to their relevance in the dermatology setting with the support of methodologists. Evidence on sex- and gender-related differences was obtained by a scoping review based on search strategies in Medline and Cochrane Library from inception to October 2021 using the following terms: arthritis, psoriatic, psoriasis, gender, and sex. The panel discussed the results and proposed strategies by consensus. Results: The scoping review identified broad themes: (1) clinical expression, (2) severity and patient-reported outcomes, (3) psychosocial impact, (4) access to treatments and propensity to treat, (5) comorbidities, and (6) treatment effect. The strategies are based on these broad themes. Limitations: No risk of bias assessment was done due to the scoping nature of the review. Conclusion: This review offers insights into gender differences in psoriasis, providing a foundation for improving clinical practice and patient outcomes.

Phage therapy for hidradenitis suppurativa: a unique challenge and possible opportunity for personalized treatment of a complex, inflammatory disease.

Phage therapy is an emerging antimicrobial treatment for critical multidrug-resistant pathogens. In this review, the specific potential and challenges of phage therapy for patients with hidradenitis suppurativa (HS) are discussed. This represents a unique challenge as HS is a chronic inflammatory disease, but presenting with acute exacerbations, which have an enormous negative impact on patient's quality of life. The therapeutic arsenal for HS has expanded in the past decade, for example, with adalimumab and several other biologicals that are currently under investigation. However, treatment of HS remains challenging for dermatologists because there are individuals who do not respond to any classes of the current treatment options when used for a first or second time. Furthermore, after several courses of treatment, a patient may lose their response to therapy, meaning long-term use is not always an option. Culturing studies and 16S ribosomal RNA profiling highlight the complex polymicrobial nature of HS lesions. Despite the detection of various bacterial species in lesion samples, several key pathogens, including Staphylococcus, Corynebacterium and Streptococcus, may be potential targets for phage therapy. Using phage therapy for the treatment of a chronic inflammatory disease could potentially provide new insights into the role of bacteria and the immune system in HS development. In addition, it is possible more details on the immunomodulatory effects of phages may come to light.

SARS-CoV-2 infection and COVID19 vaccination across eight immune-mediated inflammatory disorders: A prospective, real-life Belgian cohort study - the BELCOMID study.

Background: The risks and impact of COVID19 disease and vaccination in patients with Immune Mediated Inflammatory Diseases (IMID) remain incompletely understood. IMID patients and particularly patients receiving immunosuppressive treatment were excluded from the original, registrational phase-3 COVID19 vaccination efficacy and safety trials. Real-world observational data can help to fill this gap in knowledge. The BELCOMID study aims to explore the interaction between IMIDs, immune-modulating treatment modalities and SARS-CoV-2 infection and vaccination in a real-life patient cohort. Methods: A multidisciplinary, prospective, observational cohort study was set up. Consecutive patients with IMIDs of the gut, joints and skin followed at two high-volume referral centers were invited. Both patients under conventional treatment or targeted immune modulating therapies were included. Patient data and serological samples were collected at 3 predefined periods (before COVID19 vaccination, before booster vaccination, after booster vaccination). Primary endpoints were positive PCR-test and SARS-CoV-2 serology reflecting previous SARS-CoV-2 infection or vaccination. Associations with IMID treatment modality and IMID disease activity were assessed. Results of the first two inclusion periods (before booster vaccination) are reported. Results: At the first inclusion period data was assessed of 2165 IMID-patients before COVID19 vaccination. At the second inclusion period, data of 2065 patients was collected of whom 1547 had received complete baseline COVID19 vaccination and 222 were partially vaccinated. SARS-CoV-2 infection rate remained low in both groups. No significant increase in IMID flare-up rate was noted in patients with prior SARS-CoV-2 infection. Multiple logistic regression analyses did not show a significant influence of IMID-treatment modality or IMID activity on SARS-CoV-2 infection risk (based on PCR positivity or N-serology). Patients treated with conventional immunomodulators, systemic steroids, and patients on advanced therapies such as biologics or small molecules, had reduced S-antibody seroconversion. S-antibody response was also lower in patients without prior SARS-CoV-2 infection and in active smokers. A subset of patients (4.1%) had no S- nor N-antibody seroconversion following complete baseline vaccination. Conclusion: The BELCOMID study results confirm the benign course of COVID19 infection and vaccination in a large real-life IMID-population. However, our results underscore the need for repeated vaccination and smoking cessation in patients with IMIDs treated with immune-modulating therapies or systemic steroids during the pandemic.

Treatment of Psoriasis in Patients With Psoriatic Arthritis: An Updated Literature Review Informing the 2021 GRAPPA Treatment Recommendations.

OBJECTIVE: Our aim was to summarize and evaluate the current quality of evidence regarding the efficacy of therapies for cutaneous psoriasis (PsO) in patients with psoriatic arthritis (PsA). METHODS: A literature search of MEDLINE, Embase, Cochrane Library databases, and conference abstracts was conducted to identify interventional randomized controlled trials in patients with PsA between February 2013 and December 2021. Studies were included if PsO outcomes included achieving at least 75% improvement in the Psoriasis Area and Severity Index and the blinded comparison period was ≥ 10 weeks. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology was employed to assess quality of the evidence to inform and update the 2021 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations. RESULTS: A total of 116 studies and 36 abstracts identified in the initial search were screened. A total of 37 studies (40 treatment arms) met the criteria for final inclusion. Phosphodiesterase 4 inhibitors, Janus kinase inhibitors, and tyrosine kinase 2 inhibitors, interleukin 17 inhibitors (IL-17i), IL-12/23i, IL-23i, and tumor necrosis factor inhibitors (TNFi) had high-quality data broadly supporting the efficacy of each class for plaque PsO over placebo. Head-to-head studies with high-quality data supported both IL-17i and IL-23i over TNFi. CONCLUSION: Several pharmacologic therapeutic classes have high-quality evidence demonstrating efficacy for cutaneous PsO in the PsA population. The findings will be integrated into the 2021 GRAPPA treatment recommendations, intended to guide selection of a therapeutic class where efficacy in 1 or more cutaneous or musculoskeletal domains is required.

Comorbid Psoriasis and Metabolic Syndrome: Clinical Implications and Optimal Management.

Purpose: To review the literature on guidance on the follow-up of psoriasis and its comorbidities and to provide practical recommendations. Patients and Methods: A PubMed search was conducted using MeSH terms and free text keywords related to "psoriasis", "obesity", "hypertension", "diabetes", "dyslipidemia", "metabolic syndrome" and "Psoriatic arthritis". The search was conducted between September 2021 and January 2022. References of selected articles were scanned to identify additional articles. Results: Recommendations on the follow-up of hypertension, obesity, dyslipidemia, type 2 diabetes, metabolic syndrome, psoriatic arthritis, non-alcoholic fatty liver disease and inflammatory bowel disease in psoriasis patients were extracted from the included articles. These data are presented in summary tables for both adults and children. A practical and feasible approach for each comorbidity is discussed. Conclusion: Awareness among dermatologists for relevant psoriasis-associated comorbidities is crucial. The dermatologist should function as gatekeeper and screen for comorbidities, in order to make timely referrals when indicated.

Real-Life Effectiveness of Apremilast for the Treatment of Psoriasis in Belgium: Results From the Observational OTELO Study.

INTRODUCTION: Apremilast is approved for the treatment of psoriasis and psoriatic arthritis. However, data on the efficacy and safety of apremilast in clinical practice are limited. We assessed the real-world use and effectiveness of apremilast in patients with moderate to severe plaque psoriasis visiting dermatologist practices in Belgium, from the perspectives of the patient and the physician. METHODS: This prospective observational study enrolled adults aged 18 years or more initiating apremilast between 6 April 2017 and 30 June 2018, per Belgian reimbursement criteria. Primary outcome was the Patient Benefit Index for Skin Diseases (PBI-S). Secondary outcomes included the Patient Global Assessment (PtGA), Dermatology Life Quality Index (DLQI), Psoriasis Area and Severity Index (PASI), and body surface area (BSA). Patients were followed up for up to 18 months. RESULTS: Overall, 122 enrolled patients received at least one dose of apremilast, of which 89 received treatment for more than 150 days and were included in the reference population. Treatment goals most frequently identified (at least 70% of patients) as "very important" in the PBI-S were related to physical impairments. After 6 months of apremilast treatment, 61-78% of patients reported they had achieved these goals; only 12.5% assessed their disease as severe (PtGA, 53.6% at apremilast initiation) and over half reported a DLQI score of 5 or less, indicating improved quality of life. As assessed by the physician, 68.4% and 35.1% of patients achieved at least a 50% and 75% reduction in PASI, respectively, at month 6. Apremilast was well tolerated with no new safety signals identified. CONCLUSIONS: Our real-world data indicate that apremilast fulfils the expectations of Belgian patients with moderate to severe psoriasis, and from the perspectives of both the patient and physician, apremilast has a positive impact on their disease. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03097003.

Venous thrombotic events in psoriasis patients: a systematic review with meta-analysis.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease associated with numerous comorbidities. Psoriasis has been linked to an increased risk of metabolic syndrome and atherosclerotic arterial disease. Inflammatory conditions are known to increase the risk of venous thromboembolism (VTE), a frequent cause of morbidity and mortality. However, the relationship between psoriasis and VTE has received little attention and existing studies have shown conflicting results. OBJECTIVES: This systematic review aims to perform a meta-analysis on VTE in psoriasis patients. METHODS: We conducted a systematic electronic search of the incidence of VTE (pulmonary embolism [PE], deep venous thrombosis [DVT] and/or retinal vein occlusion [RVO]) in psoriasis patients on PubMed, Web of Science, Embase and Cochrane (specifics: see Appendix 1 in Supporting information). Only English literature and full manuscripts were included; abstracts were excluded. Pooled risk ratio and 95% confidence interval were calculated using Review Manager. RESULTS: Seven articles were included. Each study separately indicated a correlation between psoriasis and VTE after adjustment for several clinical parameters. The confounders included in the adjustment differed between studies, but all included adjustment for age, gender and comorbidities. A meta-analysis of the unadjusted data of the five studies that reported raw data on number of VTE events and patient follow-up (person-years) showed a pooled risk ratio for VTE and psoriasis of 1.29 (95% CI: 0.92-1.81). The statistical heterogeneity was high with I2 of 97%. CONCLUSIONS: Published data adjusted for key confounders demonstrate in general a significantly increased prevalence of VTE in psoriasis patients. Both psoriasis severity and number of confounders assessed seem to have an impact on this correlation. In this review, we pooled unadjusted data of the studies and we found a non-significant increased risk for VTE in psoriasis patients compared to healthy controls. This discrepancy suggests that psoriasis severity, age, gender or comorbidities may influence the risk of VTE in subgroups of the psoriasis population. Future research to identify subgroups at risk for VTE is warranted.Key messagesThe included studies reported an increased risk of VTE, DVT, PE and RVO in psoriasis patients.A meta-analysis was performed on five studies that reported raw data and showed that the pooled risk ratio for VTE in psoriasis patients overall was increased, however not significantly, compared to healthy controls.Further research to pinpoint psoriasis subgroups at risk (e.g. severe psoriasis patients, younger age, associated comorbidities) of developing VTE is warranted.

The Use of Metrics in Daily Practice and the Perception of Psoriasis-Associated Comorbidities: Discrepancies Between Research and Real-World.

OBJECTIVE: To assess the feasibility of the future implementation of a recently published Belgian treat-to-target scoring in daily practice, we investigated to what extent Belgian dermatologists use metrics and take comorbidities into account in the follow-up of psoriasis patients. METHODS: Belgian dermatologists were addressed to fill out an online questionnaire in April 2020. RESULTS: A total of 149 dermatologists completed the survey. About 55% (n = 78) indicated to do a full-body examination during every visit. Psoriasis Area Severity Index (PASI) was the most frequently used clinical score: 25% (n = 35) and 61% (n = 87) indicated to use it every visit or sometimes (>1/year), respectively. The most frequently used patient-reported outcome scoring system was the Dermatology Life Quality Index: 35% use it sometimes. Overall, there is awareness for the association with metabolic syndrome. CONCLUSION: Among tools for follow-up on moderate-to-severe psoriasis patients, Belgian dermatologists most frequently apply full-body examination and PASI score. Patient-reported outcome scoring systems are used infrequently. Psoriasis is perceived as a disease with comorbidities beyond the skin, especially obesity and hypertension. These real-world data on the use of clinical scores and PROs indicate a discrepancy from the academic setting in which new drugs are developed and evaluated. Furthermore, these data are imperative to estimate the feasibility of implementing a treat-to-target strategy published earlier by a Belgian expert group.