Psoriasis Research Articles

Value of ultrasound-assessed dactylitis in the early diagnosis of psoriatic arthritis.

The primary objective of this prospective, longitudinal, observational, single-centre study was to evaluate the association between ultrasound-assessed lesions of dactylitis and the diagnosis of psoriatic arthritis (PsA) in patients with psoriasis (PsO) and hand arthralgia. We included adult patients diagnosed with PsO with hand arthralgia, with or without other musculoskeletal complaints. They were clinically assessed at baseline, 6 and 12 months by a rheumatologist blinded to the ultrasound findings. At baseline, patients underwent a B-mode (BM) and power Doppler (PD) ultrasound assessment by other rheumatologist blinded to clinical data. The ultrasound evaluation included bilateral detection and scoring of synovitis (3 joints, 0-3), tenosynovitis (flexor tendons, 0-3), enthesitis (9 sites, 0-1), peri‑extensor tendon inflammation (PETI) (0-3), and subcutaneous tissue inflammation (SCTI) (0-3) in the 2nd-5th fingers. Seventy patients [44 women; mean (SD) age 51 (12.4) years] were included, of whom 64 completed the study. Of these, 15 (23.4 %) were diagnosed with PsA during the 12-month follow-up period. At finger level, the presence and amount of baseline BM and PD synovitis, BM tenosynovitis, BM and PD enthesitis, and BM and PD PETI were associated with PsA diagnosis (p < .05). A predictive model including two variables, presence of PD synovitis and BM enthesitis, was found to predict PsA diagnosis (χ2 = 35.38; p < .001) with an accuracy of 89.1 %, a sensitivity of 86.7 % and a specificity of 89.8 %. Ultrasound-assessed lesions of dactylitis were associated with a diagnosis of PsA and the short-term development of PsA in patients with PsO and hand arthralgia.

Glycobiology of psoriasis: A review.

Psoriasis is a chronic inflammatory skin disease with etiologies related to genetics, immunity, and the environment. It is characterized by excessive proliferation of keratinocytes and infiltration of inflammatory immune cells. Glycosylation is a post-translational modification of proteins that plays important roles in cell adhesion, signal transduction, and immune cell activation. Abnormal glycosylation is associated with inflammation, tumors, autoimmunity, and several diseases. Glycan profiles and glycosylation-related enzymes are altered in patients with psoriasis. Specific glycan structures, such as glycosaminoglycans and gangliosides, inhibit the development of psoriasis through various pathways. Lectins are glycan-binding proteins that are widely involved in the pathogenesis of psoriasis. The differential serum, epidermal, and dermal expression of galectins in patients with psoriasis distinguishes psoriasis from other nonspecific psoriasis-like dermatitis. This article summarizes relevant literature on psoriasis-related glycans to help clarify the potential molecular mechanisms of psoriasis and identify novel biomarkers and targets for the treatment of psoriasis.

Genetically mimicked effects of evinacumab on psoriasis: a drug target Mendelian randomization study.

Dyslipidemia has been reported to contribute to the psoriasis pathogenesis. Thus, evinacumab, a novel lipid-lowering drug targeting angiopoietin-like 3, may have therapeutic potential to treat and/or manage psoriasis. Summary statistics were obtained from genome-wide association studies addressing psoriasis (FinnGen Consortium; n=216,752) and serum lipid concentrations (United Kingdom Biobank; n=403,943-440,546). Two-sample Mendelian randomization analyses were conducted to evaluate the associations of serum lipid concentrations and genetically mimicked effects of evinacumab, respectively, with the risks of psoriasis and its subtypes. Genetically determined per standard deviation increase in triglyceride concentrations was associated with increased risk of psoriasis (OR: 1.17, 95% CI: 1.03-1.32, p=0.018), whereas that in low-density lipoprotein-cholesterol (LDL-C) was associated with both psoriasis (OR: 1.22, 95% CI: 1.05-1.43, p=0.011) and its subtypes, including arthropathic psoriasis (OR: 1.30, 95% CI: 1.02-1.65, p=0.032), psoriasis vulgaris (OR: 1.87, 95% CI: 1.16-2.99, p=0.0095), and guttate psoriasis (OR: 2.19, 95% CI: 1.17-4.07, p=0.014). Moreover, genetically mimicked effects of evinacumab, via angiopoietin-like 3 inhibition, significantly reduced the risk of psoriasis (OR: 0.752 per standard deviation reduction in triglycerides, 95% CI: 0.577-0.982, p=0.036) and arthropathic psoriasis (OR: 0.266 per standard deviation reduction in LDL-C, 95% CI: 0.0886-0.799, p=0.018). The genetically mimicked effect of evinacumab has the potential to reduce the risk of psoriasis and arthropathic psoriasis by lowering circulating triglyceride and LDL-C concentrations, respectively. These findings suggest that evinacumab may help prevent psoriasis and psoriatic arthritis progression in clinical practice.

Interleukin-23 versus Interleukin-17 Inhibitors in Preventing Incidental Psoriatic Arthritis in Patients with Psoriasis: A Real-World Comparison From the TriNetX US Collaborative Network.

Psoriatic arthritis (PsA) is a common comorbidity in patients with psoriasis (PsO) that leads to significant disease burden. Biologic therapies targeting the interleukin (IL)-23/IL-17 axis have been widely used for PsO, but their comparative effectiveness in preventing PsA remains unclear. The study objective was to compare the occurrence of developing incidental PsA among PsO patients treated with interleukin-23 inhibitors (IL23is) or interleukin-17 inhibitors (IL17is). A retrospective cohort study was conducted using real-world data from the TriNetX US Collaborative Network, including 53 healthcare organizations. Adult PsO patients treated with IL23is or IL17is between January 2019 and June 2022 were identified. Cox regression analysis was used to assess the risk of PsA incidence, with hazard ratios (HRs) and 95% confidence intervals (CIs) reported. Subgroup analyses were performed based on age, sex, and ethnicity. Sensitivity analyses included comparisons with tumor necrosis factor (TNF) inhibitors (TNFis) to ensure robustness. A total of 4,580 PsO patients were included in the study, with 2,273 receiving IL23is and 2,307 receiving IL17is. Treatment with IL23is was associated with a significantly lower incidence of PsA compared to IL17is (HR = 0.60, 95% CI 0.44-0.82, P = 0.001). This reduction in risk was particularly notable in the 41- to 65-year age group (HR = 0.42, 95% CI 0.27-0.64, P < 0.001) and among females (HR = 0.57, 95% CI 0.38-0.86, P = 0.007). Subgroup analyses based on ethnicity revealed varying outcomes, with White patients showing a significant risk reduction (HR = 0.55, 95% CI 0.38-0.79, P = 0.001) but no significant risk reduction was observed in Black or African American patients (HR = 1.37, 95% CI 0.37-5.13, P = 0.637). Sensitivity analyses comparing IL23is and TNFis confirmed the robustness of the findings. IL23is are associated with a lower risk of PsA incidence compared to IL17is in PsO patients, particularly in specific age, sex, and ethnic groups. These findings suggest that IL23is may be more suitable for PsO patients at high risk of PsA and could inform potential updates to treatment guidelines. Further research should focus on refining therapeutic strategies by incorporating patient-specific factors such as comorbidities, ethnicity, and genetic predispositions, which could optimize biologic selection and enhance PsA prevention efforts in clinical practice.

Efficacy and safety of various drug combinations in treating plaque Psoriasis: A meta-analysis

Efficacy and safety of various drug combinations in treating plaque Psoriasis: A meta-analysis

Portuguese consensus on first line treatment of moderate-to-severe psoriasis with a non-TNF inhibitor therapy – a delphi methodology

Introduction Psoriasis (PsO) is a common chronic, inflammatory, immune-mediated disease. In 2023, a 4.4% prevalence of PsO was reported in Portugal. Currently, Tumor Necrosis Factor inhibitors (TNFi) are the recommended first-line (1 L) biologic agents in Portugal given their lower cost. However, TNFi may not be suitable for several patients. In these patients, interleukin inhibitors (ILi) should be considered as they provide more effective outcomes and a better safety profile. Methods Qualitative interviews with PsO experts were conducted to identify PsO biologic treatment needs, resulting in an online survey to explore clinical cases focused on subpopulations of PsO. A delphi study evaluated consensus on clinical criteria to initiate non-TNFi therapy in seven predefined subpopulations of patients. Results This study highlights the benefit of starting non-TNFi therapy in all PsO predefined subpopulations. Patients with infection risk, mild heart failure and associated comorbidities, autoimmune diseases and family history of demyelinating disease consensually benefit from starting non-TNFi therapy in 1 L. Several risks associated with latent tuberculosis, advanced age and oncological disease were also evaluated. Conclusion Given the existence of various risks associated with TNFi usage, this clinical perspective overview of Portuguese experts in PsO treatment emphasizes the need for a tailored therapeutic framework in the management of PsO.

Factors predisposing to limited flexion after total hip arthroplasty for the treatment of axial spondyloarthritis.

Hip involvement is a common condition in about one-third of patients with axial spondyloarthritis (axSpA). We assessed the incidence of possible factors that predispose patients to limited flexion after total hip arthroplasty (THA) for the treatment of axSpA. We retrospectively reviewed 516 patients with axSpA (759 hips) who underwent THA. Baseline patient demographics and clinical, laboratory, and surgery-related parameters were retrospectively collected. The preoperative and latest follow-up Harris hip score (HHS) and hip flexion ability were compared. After documenting the degree of postoperative hip flexion at the latest follow-up visit, we classified hips into good flexion group (> 90°) and poor flexion group (≤ 90°). The differences of baseline parameters between good flexion and poor flexion group were examined. Then those baseline parameters with P < 0.1 in intergroup comparisons were further included into the multivariate logistic models. The median duration of follow-up was 118.5months (range, 25.0-269.1months). The median HHS increased from 36.0 (25.0, 44.0) before surgery to 85.0 (77.0, 92.0) at the latest follow-up visit (P < 0.001). At the latest follow-up visit, 406 hips (53.5%) had hip flexion > 90°. The patients who were somewhat dissatisfied represented 147 hips (19.4%), and those who were very dissatisfied represented 46 hips (6.1%). The primary cause of dissatisfaction was limited range of motion (ROM) (323 hips, 80.1%). The multivariate logistic regression model revealed that the significant variables for postoperative poor hip flexion were the younger age of disease onset (OR = 0.967; P = 0.024), psoriasis (PSO) (OR = 2.071; P = 0.007), elevated C-reactive protein (CRP) (OR = 1.031; P < 0.001), and the lack of direct anterior approach (DAA) (OR = 0.372; P = 0.015). Although THA reconstruction for axSpA patients with end-stage hip involvement achieved encouraging clinical outcomes, it was prone to a restriction of hip flexion, which is closely associated with patient satisfaction. The younger age of disease onset, PSO, elevated CRP and the lack of DAA were significantly associated with limited postoperative hip flexion. Key Points • The restriction of hip flexion after THA reconstruction for axSpA patients is closely associated with patient satisfaction. • The younger age of disease onset, PSO, elevated CRP and the lack of DAA were significantly associated with limited postoperative hip flexion.

Cross-sectional study of proteomic differences between moderate and severe psoriasis

Although an ongoing understanding of psoriasis vulgaris (PV) pathogenesis, little is known about the proteomic differences between moderate and severe psoriasis. In this cross-sectional study, we evaluated the proteomic differences between moderate and severe psoriasis using data-independent acquisition mass spectrometry (DIA-MS). 173 differentially expressed proteins (DEPs) were significantly differentially expressed between the two groups. Among them, 85 proteins were upregulated, while 88 were downregulated (FC ≥ ± 1.5, P < 0.05). Eighteen DEPs were mainly enriched in the IL − 17 signalling pathway, Neutrophil extracellular trap formation, Neutrophil degranulation and NF − kappa B signalling pathway, which were associated with psoriasis pathogenesis. Ingenuity pathway Analysis (IPA) identified TNF and TDP53 as the top upstream up-regulators, while Lipopolysaccharide and YAP1 were the top potential down-regulators. The main active pathways were antimicrobial peptides and PTEN signalling, while the inhibitory pathways were the neutrophil extracellular trap pathway, neutrophil degranulation, and IL-8 signalling. 4D-parallel reaction monitoring (4D-PRM) suggested that KRT6A were downregulated in severe psoriasis. Our data identify Eighteen DEPs as biomarkers of disease severity, and are associated with IL − 17 signalling pathway, Neutrophil extracellular trap formation, NF − kappa B signalling pathway, and defence response to the bacterium. Targeting these molecules and measures to manage infection may improve psoriasis’s severity and therapeutic efficacy.

Histone Modifications and DNA Methylation in Psoriasis: A Cellular Perspective.

In recent years, epigenetic modifications have attracted significant attention due to their unique regulatory mechanisms and profound biological implications. Acting as a bridge between environmental stimuli and changes in gene activity, they reshape gene expression patterns, providing organisms with regulatory mechanisms to respond to environmental changes. A growing body of evidence indicates that epigenetic regulation plays a crucial role in the pathogenesis and progression of psoriasis. A deeper understanding of these epigenetic mechanisms not only helps unveil the molecular mechanisms underlying the initiation and progression of psoriasis but may also provide new insights into diagnostic and therapeutic strategies. Given the unique roles and significant contributions of various cell types involved in the process of psoriasis, a thorough analysis of specific epigenetic patterns in different cell types becomes a key entry point for elucidating the mechanisms of disease development. Although epigenetic modifications encompass multiple complex layers, this review will focus on histone modifications and DNA methylation, describinghow they function in different cell types and subsequently impact the pathophysiological processes of psoriasis. Finally, we will summarize the current problems in research concerning histone modifications and DNA methylation in psoriasis and discussthe clinical application prospects and challenges of targeting epigenetic modifications as therapeutic strategies for psoriasis.

Case report: Dupilumab-induced linear psoriasis: a rare presentation

A 42 year-old male with prurigo nodularis treated with dupilumab showed a case of linear psoriasis, highlighting the potential of dupilumab to induce immune shift and chimeric gene expression.

Bimekizumab efficacy and safety through 3 years in patients with moderate to severe plaque psoriasis: Long-term results from the BE RADIANT phase 3b trial open-label extension period.

Overexpression of interleukin (IL)-17A and IL-17F significantly influences psoriasis pathology. Until recently, biologics targeting IL-17A alone, like secukinumab, were used to treat psoriasis. Bimekizumab is a monoclonal IgG1 antibody that targets both IL-17A and IL-17F. BE RADIANT was the first phase 3 study to investigate switching from selective inhibition of IL-17A to dual inhibition of IL-17A and IL-17F.Bimekizumab has previously shown superior achievement of complete skin clearance (PASI 100) versus secukinumab through 48 weeks. Switching from secukinumab to bimekizumab resulted in improved clinical responses. Over 2 years, no new safety signals were observed. To report 3-year efficacy and safety of bimekizumab in patients with moderate to severe plaque psoriasis receiving continuous bimekizumab, or switching from secukinumab after 1 year. The BE RADIANT phase 3b randomised controlled trial had a 48-week double-blinded period, in which patients received bimekizumab (320 mg every 4 weeks [Q4W]), or secukinumab (300 mg weekly to Week 4, then Q4W). At Week 16, bimekizumab-randomised patients underwent re-randomisation to receive Q4W or Q8W maintenance dosing. From Week 48 onwards (open-label extension), all received bimekizumab. 336 bimekizumab- and 318 baseline secukinumab-randomised patients entered the open-label extension. Among these, more bimekizumab-randomised patients achieved PASI 100 (modified non-responder imputation) at Year 1 (74.9%) versus secukinumab-randomised patients (52.8%). PASI 100 response rates were maintained over 3 years in bimekizumab-treated patients (68.8%) and increased in secukinumab-randomised patients switching to bimekizumab (68.8%).Bimekizumab was well-tolerated to 3 years. In patients receiving ≥1 bimekizumab dose, the most common treatment-emergent adverse events (TEAEs) over 3 years were nasopharyngitis, oral candidiasis, and upper respiratory tract infection (exposure adjusted incidence rates: 12.2, 10.0, and 5.5/100 patient-years, respectively). Rates of TEAEs of interest, including serious infections, inflammatory bowel disease, and suicidal ideation and behaviour, did not increase with longer exposure to bimekizumab from 1 to 3 years. Over two-thirds of bimekizumab-randomised patients and those switching from secukinumab to bimekizumab achieved and maintained complete skin clearance over 3 years of treatment. Over 3 years, bimekizumab was well-tolerated, and TEAE rates did not increase with longer exposure.

Management of Systemic Anti-psoriatic Drugs in PsoriasisPatients with ConcurrentParaplegia or Tetraplegia: Insights From a 6-Year Multicenter, Retrospective Observational Study.

Patients with psoriasis (PsO) and permanent spinal cord injuries (SCI) resulting in paraplegia and tetraplegia may experience a higher rate of infections compared to patients with PsO without SCI. It can result in further challenges for therapeutic management with immunosuppressants (biological and non-biological treatments). Thus, weaimed to evaluate the rate of infections in patients with PsO and SCI treated with systemic immunosuppressants. This multicenter, retrospective observational study enrolled patients with PsO and traumatic SCI undergoing systemic immunosuppressive treatments for at least 5years. All patients were evaluated by experienced, board-certified dermatologists and neurologists. Demographic and clinical data were collected. We enrolled 23 patients with SCI (16 with paraplegia and 7 with tetraplegia) treated with methotrexate (MTX) and different biologics (tumor necrosis factor (TNF) inhibitors (i) and interleukin (IL)-17i/IL-23i). Globally, patients with SCI treated with MTX displayed higher rates of infection compared to those treated with biologics. Patients with paraplegia had lower rates of infection compared to patients with tetraplegia during anti-psoriatic therapies (p < 0.05). Those treated with TNFi had greater rates of infection than those treated with IL-17i/IL-23i (p < 0.001). Patients with psoriatic arthritis (PsA) experienced a significant diagnostic delay and clinical monitoring of PsA severity was challenging. In patients with moderate-to-severe PsO and concurrent traumatic SCI, dermatologists should consider using IL-17i/IL-23i as first-line therapy.

Real-Life Experience with Tildrakizumab in Plaque Psoriasis with Palmoplantar Involvement: A Multi-Center Retrospective Italian Study.

Palmoplantar psoriasis (PPp) has a profound negative impact on patients' quality of life, and it represents a therapeutic challenge, as palms and soles are difficult to treat area. Although the efficacy profile of tildrakizumab has been well evaluated in the literature, data on its use for PPp are still limited. The objective of the study was to evaluate the efficacy and safety of tildrakizumab on moderate-to-severe plaque psoriasis with involvement of the palmoplantar area. A multicenter, retrospective, real-life study was performed enrolling patients with moderate-to-severe plaque psoriasis involving the palmoplantar area undergoing treatment with tildrakizumab with a follow-up of at least 52weeks. At baseline, demographic and clinical data were assessed. Psoriasis severity was evaluated by using Psoriasis Activity Severity Index (PASI), body surface area (BSA), Psoriasis Global Assessment (PGA), Pruritus-Numerical Rating Scale (P-NRS) and Dermatology Life Quality Index (DLQI). Palmoplantar PASI (ppPASI) was used to evaluate psoriasis severity in the palmoplantar region. Clinical improvement was evaluated at each follow-up visit [week (W) 4, 16, 52]. A total of 99 patients were enrolled. A reduction in PASI, BSA, PGA, P-NRS and DLQI was observed at each time point. Mean ppPASI at baseline was 16.9 ± 13.2, which started to improve at W4 (8.9 ± 9.1) and continued to decrease at W16 (2.1 ± 3.1) and W52 (0.5 ± 1.0). Moreover, a sub-analysis showed that the probability of achieving ppPASI50 at W4 increased in case of nail psoriasis (p < 0.05) and decreased in bio-experienced patients (p < 0.001). Similarly, the probability of achieving ppPASI75 at W4 decreased in the case of prior biologic exposure (p < 0.05). Finally, patients with nail psoriasis showed a higher probability of reaching ppPASI75 at W16 (p < 0.05), whereas patients previously treated with systemic therapies for psoriasis reported a reduced probability of ppPASI75 achievement at this time point (p < 0.05). Tildrakizumab was shown to be a fast and effective treatment for patients with PPp, being able to achieve significant results already after only 4weeks of treatment. Moreover, the identification of potential clinical factors predictive of response may improve the selection of the best treatment in patients with PPp.

Long-Term Safety of Ixekizumab Treatment in Patients with Psoriasis, Psoriatic Arthritis, or Axial Spondyloarthritis: a PostHoc Analysis of Cerebro-Cardiovascular Events.

Psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) may confer an increased risk for cardiovascular (CV) disease, including major adverse cerebro-cardiovascular events (MACE), deep vein thrombosis (DVT), and pulmonary embolism (PE). Patients with these conditions are often exposed for extended time periods to biologics, such as ixekizumab (IXE). Therefore, understanding the risk of CV events, especially MACE, in patients with PsO, PsA, and axSpA exposed to IXE is important. The incidence of MACE (i.e., adjudicated cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke), DVT, and PE was assessed in adults who received ≥ 1 dose of IXE across 25 randomized clinical trials (17 PsO, 4 PsA, 4 axSpA). Rates of CV events were analyzed for pooled studies by indication and analyzed from treatment initiation up to the end of the study program. Exposure-adjusted incidence rates per 100 patient-years (IR/100PY) are reported. This integrated safety analysis included 6892 patients with PsO, 1401 with PsA, and 932 with axSpA. The median duration of IXE exposure was 478.5days (1.3years) for patients with PsO, 504.5days (1.4years) for patients with PsA, and 981.0days (2.7years) for patients with axSpA. The incidence of adjudicated MACE was low (IR/100PY: PsO = 0.5; PsA = 0.5; axSpA = 0.3) and stable over the treatment periods. The most common types of MACE reported were non-fatal myocardial infarction (IR/100PY: PsO = 0.3; PsA = 0.3; axSpA = 0.3), followed by non-fatal stroke (IR/100PY: PsO = 0.1; PsA = 0.2; axSpA = 0.0), and cardiovascular death (IR/100PY: PsO = 0.1; PsA = 0.1; axSpA = 0.0). The incidences of DVT (IR/100PY: PsO = 0.1; PsA = 0.1; axSpA = 0.1) and PE (IR/100PY: PsO = 0.1; PsA = 0.0; axSpA = 0.0) were low. This integrated safety analysis of 25 randomized clinical trials showed that the incidence of adjudicated MACE was low among adult patients with PsO, PsA, and axSpA and that the rates did not increase with increasing IXE exposure. The supplementary TableS1 provides a comprehensive list of clinical trials and their registration numbers.

Multi-omics analysis reveals novel causal pathways in psoriasis pathogenesis

BackgroundTo elucidate the genetic and molecular mechanisms underlying psoriasis by employing an integrative multi-omics approach, using summary-data-based Mendelian randomization (SMR) to infer causal relationships among DNA methylation, gene expression, and protein levels in relation to psoriasis risk.MethodsWe conducted SMR analyses integrating genome-wide association study (GWAS) summary statistics with methylation quantitative trait loci (mQTL), expression quantitative trait loci (eQTL), and protein quantitative trait loci (pQTL) data. Publicly available datasets were utilized, including psoriasis GWAS data from the European Molecular Biology Laboratory–European Bioinformatics Institute and the UK Biobank. Heterogeneity in dependent instruments (HEIDI) test and colocalization analyses were performed to identify shared causal variants, and multi-omics integration was employed to construct potential regulatory pathways.ResultsOur analyses identified significant causal associations between DNA methylation, gene expression, protein abundance, and psoriasis risk. We discovered two pathways involving the long non-coding RNA RP11-977G19.11 and apolipoprotein F (APOF). Methylation at sites cg26804944 and cg02705573 was negatively associated with RP11-977G19.11 expression. Reduced expression of RP11-977G19.11 was linked to increased APOF levels, which were positively associated with a higher risk of psoriasis. Methylation at sites cg00172967, cg00294382, and cg24773560 was positively associated with RP11-977G19.11 expression. Elevated expression of RP11-977G19.11 was associated with decreased APOF levels, reducing the risk of psoriasis. Colocalization analysis highlighted APOF as a key protein in psoriasis pathogenesis. Validation using skin tissue, EBV-transformed lymphocytes data and inflammation-related protein panels confirmed the associations of RP11-977G19.11 and APOF with psoriasis.ConclusionsOur multi-omics analysis provides preliminary evidence for potential molecular mechanisms in psoriasis pathogenesis. Through the integration of GWAS and molecular QTL data, we identify candidate pathways that may be relevant to disease biology. While these findings require extensive experimental validation, they offer a framework for future investigations into the molecular basis of psoriasis.

P0946 Switching from intravenous to subcutaneous Infliximab in patients with immune mediated diseases in clinical remission

Abstract Background We aimed to report on the efficacy and safety of elective switching from intravenously (IV) to subcutaneously (SC) administered Infliximab (IFX) in patients with immune mediated diseases. Methods This was a multicenter retrospective study in which we analyzed data collected from consecutive patients with immune mediated diseases treated in a hospital setting. Each hospital department was considered a study center and overall, 8 gastroenterology departments, 6 rheumatology departments and 1 dermatology department from 13 Greek hospitals, that are all referral centers, recruited patients for the study. Patients with Crohn’s disease (CD), Ulcerative Colitis (UC), Spondyloarthritis (SpA), Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA) and chronic plaque Psoriasis (PsO) who were receiving IFX-IV for maintenance of remission and were switched to IFX-SC based on their physician’s choice were included. All patients with gastrointestinal and skin diseases were in clinical remission, while those with musculoskeletal disease had inactive disease or low disease activity. The primary endpoint was disease deterioration during the follow up period, according to disease specific composite measures. Results Between April 2023 and April 2024, a total of 344 patients (CD=136, UC=62, SpA=52, PsA=38, RA=7, PsO=44, co-existence of more than one disease=5) were switched from IFX-IV to IFX-SC. The mean duration of treatment with IFX before switching was a mean (SD) 53.7 (36.2) months. Eleven patients (3.2%) were receiving combination treatment with an immunomodulator and 2 patients (0.6%) were using oral or iv steroids at the time of switch. After a mean (SD) follow up period of 8 (4) months, 12 patients (3.5%) discontinued treatment with IFX-SC. Five of them (1.5%) because of disease worsening and the remaining 7 (2.0%) because of the occurrence of side effects. All other 332 patients (96.5%) showed favorable response, none of them requested an unscheduled visit, or developed an adverse event (clinical or laboratory) or needed escalation of treatment. Conclusion Elective switching from IFX-IV to IFX-SC seems to be an effective and safe approach in real-world every day clinical practice to maintain long-term clinical remission, inactive disease or low disease activity in patients with immune-mediated diseases.

P0879 The totality of evidence for FYB202 – an EU-approved and US-licensed biosimilar to reference ustekinumab

Abstract Background Ustekinumab is a fully human IgG1/kappa monoclonal antibody to interleukin (IL)-12/23. It is authorized for the treatment of moderate to severe plaque psoriasis, active psoriatic arthritis, and active inflammatory bowel disorder. FYB202 has been approved by both EMA and FDA in September 2024 as a biosimilar to reference ustekinumab based on extensive comparative analytical characterization data and the proof of equivalence in clinical performance. Methods A full set of critical quality attributes was investigated with a comprehensive set of analytical methods. Functional comparability of FYB202 to the reference product for the main mechanism of action was assessed with IL-12 and IL-23 binding and bioassays. Equivalence in PK and efficacy as well as similarity in safety, tolerability, and immunogenicity were evaluated in clinical trials in healthy subjects and psoriasis patients. Results FYB202 was found to be analytically similar to reference ustekinumab with respect to physicochemical and biological properties, including structure, function, purity, and potency. Most relevant potency results are shown in Figure 1. A 3-arm PK study in 491 healthy volunteers demonstrated PK equivalence between FYB202 and both EU-approved and US-licensed ustekinumab and between the two reference drugs (all 90% CIs were within the predefined equivalence margin of 80 to 125% (Balser1). FYB202 was shown to be equivalent to reference ustekinumab in 392 patients with moderate-to-severe plaque psoriasis, with the mean percent improvement in PASI score from baseline to week 12 within the predefined equivalence intervals for both the EU- and US-specific analyses. The similarity in response was maintained over the whole course of the study. Transitioning from reference product to FYB202 had no clinically relevant effect on efficacy, safety, or immunogenicity (Papp2). Conclusion FYB202 has been shown to have similar physicochemical and functional properties and equivalent clinical performance was shown in clinical studies. Based on a totality of evidence approach, proof of therapeutic equivalence in the sensitive psoriasis population allows for extrapolation to other indications, with similar clinical performance of FYB202 and reference ustekinumab assumed across all approved indications. FYB202 provides a safe and effective biosimilar alternative for patients in need of ustekinumab therapy.

P0276 Psoriasis is more frequently induced and displays a distinct phenotype in patients with Inflammatory Bowel Disease.

Abstract Background Specific psoriasis (Pso) phenotypes seem to emerge in inflammatory bowel disease (IBD) patients. Our study explored Pso phenotypes under and outside biologic therapy in IBD, comparing them to those in chronic inflammatory rheumatism (IRD). Methods From a prospective university hospital cohort of patients with IBD, IRD, and Pso, we selected those with IBD and/or IRD (axial and peripheral spondyloarthritis or rheumatoid arthritis) associated with Pso, excluding psoriatic arthritis cases. Each case was reviewed to classify psoriasis as therapy-induced or not, define prevalence with phenotype description, examine treatments responsible for induced Pso, and assess risk factors for therapy-induced Pso in IBD. Results Among 2,412 patients in the database, 237 (9.8%) had psoriasis associated with IBD and/or IRD: 98 with IBD, 110 with IRD, and 29 with both IBD and IRD. Pso prevalence was 12.1% in IBD vs. 8.5% in IRD (p=0.0056). After analysis, 92 (93.9%) IBD and 86 (78.2%) IRD patients had been exposed to systemic therapy (p=0.0013). The mean age for IBD+Pso and IRD+Pso was 46.4 (±15.8) and 52.8 (±15.5) years, respectively (p=0.0034); 62 (63.3%) and 49 (45%) were women (p=0.0083). Phenotypic details of Pso were available in 97/98 IBD and 90/110 IRD cases: 70 (71.4%) vs. 33 (30%) were therapy-induced Pso, respectively (p&amp;lt;0.0001). The main systemic therapy linked to induced Pso was biologics: adalimumab in 44 (62.9%) IBD and 15 (45.5%) IRD patients (p=0.0957). Plaque and inverse psoriasis were noted in 72 (73.5%) and 39 (39.8%) IBD vs. 53 (48.2%) and 6 (5.4%) IRD patients (p=0.0002 and p&amp;lt;0.0001). Lesions appeared on the face in 26 (26.5%) IBD vs. 6 (5.4%) IRD (p&amp;lt;0.0001), on the scalp in 40 (40.8%) IBD vs. 30 (27.3%) IRD (p=0.0391), and on nasal wings in 13 (13.3%) IBD patients only (p&amp;lt;0.0001), suggesting this as a specific site. In IBD, inverse and scalp Pso were more frequent in therapy-induced cases. Regarding Pso treatments, biologic therapy was discontinued in 13 (13.3%) IBD patients vs. 2 (1.8%) IRD patients (p=0.0014), and a swap out of biologic class was made in 32 (32.7%) IBD patients vs. 5 (4.5%) IRD patients (p&amp;lt;0.0001). Factors associated to therapy-induced Pso in IBD were active smoking (OR= 2.02, 95% CI [1.14–3.56], p=0.0193), inflammatory phenotype in Crohn’s disease (OR=1.94, 95% CI [1.21;3.10], p=0.0047), and female sex (OR=2.04 [1.25–3.31], p=0.0041). Conclusion In this large cohort, Pso prevalence in IBD was high, with therapy-induced Pso being more frequent among women and smokers. Specific phenotypes were observed (induced, inverse, scalp, nasal wings), suggesting a common pathophysiology with the underlying inflammatory disease.

The Impact of Family History on Clinical Presentation and Biologic Treatment Response in Patients with Psoriasis: A Multicenter Prospective Cohort Study.

Family history (FH) of psoriasis has been implicated as a risk factor for developing psoriasis. However, whether FH also carries information on clinical presentation and treatment response to biological agents in patients with psoriasis remains unclear. This prospective, multicenter observational study aimed to analyze the clinical presentation and efficacy differences between patients with psoriasis with and without a FH. The SPEECH registry is an observational, multicenter, and prospective registry that has been collecting data on psoriasis treatment since November 2022. This study included adult patients diagnosed with moderate-to-severe plaque psoriasis initiating treatment with biologics, including guselkumab, secukinumab, ixekizumab, ustekinumab, and adalimumab. FH of psoriasis was identified through patient self-report in which a positive FH was defined as a first-degree relative having psoriasis. The primary outcome measures include 75% improvement in Psoriasis Area and Severity Index (PASI75) and the Physician's Global Assessment score of cleared/minimal (PGA 0/1) after 3 months of treatment. Logistic regression was employed to determine the adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the achievement of response in selected outcomes for patients with a FH compared with those without a FH. The study included a total of 859 patients, of whom 22.9% had a FH of psoriasis. Patients with psoriasis who had a FH experienced an earlier onset of the disease and more severe anxiety symptoms than those without a FH. After 3 months of treatment, patients with psoriasis with a FH exhibited a higher likelihood of achieving PASI75 (aOR 1.60 [95% CI 1.02, 2.51]) and PGA 0/1 (aOR 1.54 [95% CI 1.03, 2.31]). Notably, these differences persisted after 6 months of treatment, confirming the sustained effectiveness of biologic treatments in patients with a positive FH. Further mediation analysis uncovered a significant indirect effect of FH on the treatment response to biologics through age of onset (p = 0.028), and the proportion mediated was 20.5%. FH of psoriasis may affect the clinical course of patients and enhance their treatment response to biologics, highlighting the importance of FH assessment in optimizing treatment outcome and guiding clinical decision of biologic selection. Future studies on biologic treatment responses in psoriasis should consider family history as a significant confounding factor. ChiCTR2000036186.

Biologic Therapy and Cardiometabolic Risk in Psoriasis: A Retrospective Review.

Psoriasis is a systemic inflammatory disease with increased cardiometabolic risk including dyslipidaemia and diabetes. Biologic therapy effectively treats the cutaneous inflammatory burden of psoriasis and evolving evidence suggests potential to reduce systemic inflammatory sequalae that can elevate cardiovascular risk. This study aimed to assess the change in cardiometabolic risk markers in a cohort of patients with psoriasis treated with 1year of continuous biologic treatment. A retrospective review was conducted of patients receiving biologic therapy for chronic plaque psoriasis in a single dermatology centre at a major tertiary hospital in Sydney, Australia. The effect of biologic therapy on psoriasis was assessed using the psoriasis area severity index (PASI). Cardiometabolic risk markers assessed included lipid profile (total cholesterol [TC], low-density lipoprotein [LDL] cholesterol, high-density lipoprotein [HDL] cholesterol and triglycerides [TG]) and haemoglobin A1c (HbA1c). Measurements at baseline and 1year were compared using paired ttests for analysis of the parameters which approximated normal distribution (TC, LDL, HDL) and Wilcoxon signed-rank test for analysis of those which did not (TG, HbA1c, PASI). Two-tailed Pvalues < 0.05 were considered significant. A total of 200 patients were reviewed, of which 39had complete data sets. The participants' ages ranged from 21 to 85years (mean 51, SD 16.9). Of the 39 participants, 31 (79.5%) were male, 8 (20.5%) were female; 26 (67%) were biologic experienced (BE) and 13 (33%) were biologic naïve (BN). The mean PASI at baseline (for BN + BE) was 13.4 (SD 9.8). The biologic agents used, according to frequency, included risankizumab, with 14 participants (35.9%), secukinumab by 7 (17.9%), ustekinumab by 6 (15.4%), ixekizumab by 6 (15.4%), guselkumab by 3 (7.7%), infliximab by 2 (5.1%), and adalimumab by 1 (2.6%). After 12months, significant skin improvement was seen [PASI reduced from 13.43 (SD 9.8) to 1.1 (SD 2.1), p < 0.001]. There was no significant change in lipid profile, including TC (mean difference -0.1mmol/L, p = 0.532), LDL-C (mean difference = -0.1mmol/L, p = 0.476), HDL (mean difference = -0.1mmol/L, p = 0.125), triglycerides (mean difference = 0.0mmol/l, p = 0.748) or HbA1c (mean difference 0.38%, p = 0.468). Markers of cardiometabolic risk (lipid profile and HbA1c) did not significantly improve after 1year of biologic therapy despite significant reduction in psoriasis skin severity. Further research in larger cohorts is needed to elucidate the benefits, if any, of biologic therapy on cardiometabolic parameters in individuals with psoriasis, in order to optimise care for this vulnerable cohort.