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Secondary failure to biologic DMARDs (bDMARDs) is challenging and contributes to the complexity of managing psoriatic arthritis (PsA). We aimed to define the frequency and incidence of this phenomenon in PsA and identify the risk factors for its occurrence.Methods
We retrieved data on PsA patients from our single-centre, specialized-care, prospective observational cohort who initiated and remained on bDMARDs for ≥1 year after clinic enrollment between 2000 and 2023. We defined response to therapy at the one-year visit (baseline) as achievement of ≥40% reduction in the swollen joint count (SJC) and either ≥50% reduction in PASI or PASI ≤2. We defined secondary failure as the inability to maintain response criteria or as the clinician's judgment of loss of effectiveness. To examine factors associated with secondary failure, we fitted Cox regression models.Results
Of 482 patients included in the study, 264 (54.8%) were responders at one year. Of these, 94 (35.6%) developed secondary failure at a median of 1.6 [IQR: 0.7, 3.8] years from response. In the multivariable model, higher SJC (HR 1.39, 95% CI 1.05-1.84) and PASI (HR 1.14, 95% CI 1.01-1.29) at baseline were associated with secondary failure. TNFi vs. other bDMARD use (HR 0.39, 95% CI 0.18-0.88), initiation as first-line bDMARD (HR 0.48, 95% CI 0.25-0.91), and treatment initiation during more recent calendar years (HR 0.34, 95% CI 0.12-0.98) were associated with less secondary failure.Conclusion
Secondary failure to bDMARDs is common in PsA and may be influenced by both disease- and therapy-related factors.Weiterlesen
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Psoriatic disease (PsD) is a chronic, multisystem, inflammatory disorder encompassing psoriasis, psoriatic arthritis (PsA), and their associated comorbidities.Objective
The aim of this subanalysis of the global "Psoriasis and Beyond" study was to evaluate patients' experiences of living with PsD in the USA.Methods
The study included a cross-sectional, quantitative, 25-min online survey of adults with self-reported, healthcare professional-diagnosed, moderate-to-severe psoriasis, with or without PsA. USA-based patients were recruited through online panels by the Institut de Publique Sondage D'Opinion Secteur and The National Psoriasis Foundation.Results
This analysis included 793 US patients with psoriasis; 43% also had PsA. Overall, 75% of patients knew that their disease was systemic, and 65% had heard the term "psoriatic disease." Of patients without diagnosed PsA, 50% screened positive for PsA using the Psoriasis Epidemiology Screening Tool. Psoriasis negatively affected emotional well-being and quality of life (QoL) in the majority of patients (87% and 91%, respectively). Overall, 29% of patients reported that they could not work or study in the week prior to the survey; of these, 98% responded that psoriasis had a very or extremely large impact on their QoL. Mean diagnostic delays of 3.7 and 3.3 years for psoriasis and PsA, respectively, were reported.Conclusions
This analysis of USA-based patients with PsD highlights the profound impact of PsD on emotional well-being and QoL and suggests potential underdiagnosis of PsA. There is a need to ensure early PsD diagnosis and to provide holistic treatment, including mental health support.Weiterlesen
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Psoriasis is associated with a significant comorbidity burden, especially cardiovascular and metabolic complications. Glucagon-like peptide-1 receptor agonists (GLP-1RA), such as semaglutide, used to treat obesity and diabetes, could potentially reduce comorbidity in patients with psoriasis.Objective
To investigate all-cause mortality, cardiovascular, inflammatory, psychiatric outcomes, and adverse events in psoriasis patients treated with GLP-1RA.Methods
This retrospective population-based cohort study utilized real-world data from the US TriNetX database. Patients with psoriasis who were treated for diabetes or obesity with GLP-1RA during the full follow-up period of 2 years were compared with those treated with other systemic anti-diabetic or obesity drugs. After 1:1 propensity-score matching for relevant risk factors, 3,048 participants were included in each cohort. The primary outcomes included the risk of cardiometabolic, psychiatric, and autoimmune sequelae of psoriasis, as well as all-cause mortality and potential adverse drug events. The analysis was repeated using cohorts without psoriasis and results were further validated through two sensitivity analyses involving (i) later follow-up periods, or (ii) exclusion of patients with pustular psoriasis.Results
In the matched cohorts of 3,048 patients with psoriasis treated with GLP-1RA (60.37% females, mean age 56.94 years, standard deviation [SD] 12.02 years) versus other antidiabetic and obesity drugs (61.91% females, mean age 56.42 years, SD 14.16 years), GLP-1RA treatment was associated with significantly decreased all-cause mortality (hazard ratio [HR] 0.219, 95% confidence interval [CI] 0.123-0.391, p<0.0001) and reduced risk for major adverse cardiac events (MACE, HR 0.561, 95% CI 0.442-0.714, p<0.0001). Additionally, lower risks for alcohol (HR 0.346, CI 0.174-0.685, p=0.009) and substance abuse (HR 0.510, CI 0.350-0.743, p=0.002) were observed. Typical adverse drug events were not more frequent in the GLP-1RA cohort. The risk reductions were more pronounced in the cohorts with psoriasis compared to persons with obesity or diabetes without psoriasis. Findings were consistent across all sensitivity analyses.Conclusions
GLP-1RA treatment was safe and associated with reduced risks of cardiovascular and psychiatric comorbidities, as well as lower mortality in patients with psoriasis, with risk reductions markedly higher than in cohorts without psoriasis. Physicians should consider this drug class for patients with psoriasis and comorbid obesity or diabetes.Weiterlesen
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Psoriasis is a chronic immune-mediated skin disease that significantly impacts patients' quality of life due to its physical, psychological, and systemic burden. Phosphodiesterase-4 (PDE-4) plays a pivotal role in the inflammatory cascade of the disease through the modulation of intracellular cyclic adenosine monophosphate (cAMP) levels. This systematic review evaluates current evidence on the clinical efficacy and safety of novel PDE-4 inhibitors in the treatment of psoriasis.Methods
A systematic search was conducted in PubMed/Medline, Ovid Embase, and Web of Science databases through January 18th, 2025, to identify clinical studies evaluating PDE-4 inhibitors in patients with psoriasis. Methodological quality and risk of bias were assessed using the National Institutes of Health (NIH) quality assessment tool and the Murad et al.quality assessment tool.Results
Out of 1,942 related studies, twelve studies with 642 patients met our inclusion criteria. Among oral PDE-4 inhibitors, oral roflumilast demonstrated consistent improvements in the Psoriasis Area and Severity Index (PASI) and the Dermatology Life Quality Index (DLQI), as well as patient-reported outcomes, in cases with moderate to severe plaque psoriasis. Gastrointestinal symptoms were the most common adverse events. Similarly, orismilast and ME3183 also demonstrated significant PASI reductions and favorable tolerability, while topical agents like crisaborole and PF-07038124 showed a rapid localized response in patients suffering from mild to moderate psoriasis, with minimal adverse effects in sensitive areas, including the face and intertriginous regions.Conclusion
PDE-4 inhibitors, both oral and topical, demonstrate promising efficacy and acceptable safety profiles in the treatment of psoriasis. To confirm their long-term benefits and improve clinical use, larger-scale studies with longer follow-up and a wider range of patients are required.Weiterlesen
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The nature of the relationship between psoriasis and alcohol consumption has been the topic of discussion for many years. Some studies have found that a higher intake of alcohol may be associated with a more severe manifestation of the disease. At the same time, patients with psoriasis often demonstrate elevated levels of alcohol consumption. It has not yet been fully established whether alcohol abuse serves as a trigger for psoriasis or if patients with psoriasis are simultaneously more prone to alcohol abuse.Objective
The objective of this study was to employ Google Trends as a tool for crowdsourcing data on a national level to explore the relationship between psoriasis and the consumption of alcohol in Sweden.Methods
This study examines crowdsourced web search data related to psoriasis and other skin disease-related search terms (such as utslag [rash]) as well as search interest in different types of alcohol. The analysis covers a 5-year period from 2018 to 2023 in Sweden, focusing on search behavior and correlations across this period.Results
The search behavior regarding psoriasis and alcohol-related search terms showed seasonal variations throughout the year. The relative search volume for psoriasis peaked in February, while alcohol-related searches, particularly Systembolaget and vodka, peaked in December and June. Our statistical analysis revealed relationships between the search interest regarding psoriasis and terms related to alcohol consumption, with disparities between different types of alcohol. The term "psoriasis" was negatively correlated with "Systembolaget" (r=-0.210), "vitt vin" (r=-0.224), and "vodka" (r=-0.220) (all P<.001), while the term "utslag" showed positive correlations with these same alcohol-related terms (r=0.278-0.347; P<.001).Conclusions
Crowdsourced data can offer valuable insights into population-level behavior. The observed negative correlations between psoriasis and alcohol-related searches suggest complex interactions, possibly reflecting reduced disease awareness or care during periods of higher alcohol consumption. The direction and strength of the correlations with psoriasis were not consistent across the different types of alcohol investigated in this study, which poses the question whether the relationship might be influenced by the type of beverage consumed. Further research is warranted to explore underlying mechanisms and validate these findings in clinical populations.Weiterlesen
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Psoriasis is an immune-mediated chronic inflammatory condition characterized by significant neutrophil infiltration in the skin. Given that the spleen is the largest peripheral immune organ in the body, it is important to investigate whether it has any impact on skin inflammation in psoriasis.Methods
To investigate this mechanism, a psoriatic mouse model was established by IMQ application. Flow cytometry and immunohistochemistry analyses were performed to determine the percentage of various immune cells in the spleen. The role of neutrophils was specifically assessed using the anti-Gr-1 antibody. Splenic granulopoiesis was evaluated using EdU labeling. To understand the spleen's role in skin inflammation, splenectomy was performed on the experimental mice. IL-6 levels were measured by ELISA, and P-STAT3 in neutrophils was detected via immunofluorescence. Further examination of IL-6's effects on neutrophil formation involved treating mice with IL-6 antibody. The severity of psoriasis was evaluated through histological staining and PASI scoring.Results
Our study revealed that the spleens of psoriatic mice were enlarged compared to those of vehicle mice. Among immune cell populations, neutrophils showed the most significant changes, with marked increases in both spleen and skin of psoriatic mice and patients, contributing to disease progression. Post-splenectomy, neutrophil infiltration in the skin was reduced by approximately 60% in psoriatic mice. This indicates that the neutrophils in the skin were primarily derived from the spleen. Additionally, the spleen showed a notable capacity for granulopoiesis with elevated neutrophils. Moreover, we found elevated IL-6 levels in the skin, blood, and spleen in the model, which was decreased after splenectomy. Treatment with an IL-6 antibody reduced neutrophil formation in both the spleen and skin, which alleviated skin inflammation in psoriatic mice. Additionally, P-STAT3 signaling was decreased following IL-6 antibody treatment. The neutrophil infiltration in spleen and skin was decreased after injection with the inhibitor of P-STAT3, which also alleviated the inflammation of psoriatic model. Thus, IL-6 served as the dominant regulator of spleen granulopoiesis, a process potentially mediated by P-STAT3 signaling.Conclusions
The spleen plays a crucial role in the immune microenvironment of psoriasis as a major site of granulopoiesis, influencing neutrophil infiltration in the skin of psoriatic mice. Additionally, IL-6 is a key regulator of neutrophil formation in the spleen of psoriatic mice, likely through P-STAT3-dependent mechanisms.Weiterlesen
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Network pharmacology and Mendelian randomization analysis of Xiao Bi decoction in treating psoriasis
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