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David Bergman,1 Bjorn Roelstraete,1 Jiangwei Sun,1 Fahim Ebrahimi,1,2 Rickard Lidström,3 Axel Svedbom,4,5 Mona Ståhle,4 Jonas F Ludvigsson1,6,7 1Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; 2Department of Gastroenterology and Hepatology, Clarunis University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland; 3Diagnostiskt Centrum Hud, Stockholm, Sweden; 4Division of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; 5Dermatology and Venereology Clinic, Karolinska University Hospital, Stockholm, Sweden; 6Department of Pediatrics, Orebro University Hospital, Orebro, Sweden; 7Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USACorrespondence: David Bergman, Email David.bergman.1@ki.seBackground: Microscopic colitis (MC) has been associated with several immune-mediated diseases including psoriasis, but earlier research has been limited to psoriasis occurring before MC. Data from large-scale cohort studies investigating MC and risk of future psoriasis are lacking.Objective: To examine the association between MC and psoriasis.Methods: In a nationwide, population-based, matched cohort study in Sweden from 2007 to 2021, we identified 8404 patients with biopsy-verified MC (diagnosed in 2007– 2017), 37,033 matched reference individuals, and 8381 siblings without MC. Information on MC was obtained through the ESPRESSO cohort (a Swedish histopathology database with nationwide coverage). Using Cox regression, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for psoriasis up until 2021.Results: During a median follow-up of 9.2 years (interquartile range = 6.7– 11.7), 179 MC patients and 440 reference individuals were diagnosed with psoriasis (241.1 vs 131.8 events per 100,000 person-years), corresponding to one extra case of psoriasis in 91 patients with MC over 10 years. After adjustment for the matching variables (birth year, sex, county of residence, and calendar period) and level of education, we computed an adjusted hazard ratio (aHR) of 1.82 (95% CI = 1.53– 2.17). Stratified by sex, estimates were similar and when examining the aHR across different lengths of follow-up, we found significantly elevated estimates up to 10 years after MC diagnosis. Compared to MC-free siblings, the aHR was 1.85 (95% CI = 1.36– 2.51).Conclusion: Patients with MC are at an almost doubled risk of psoriasis compared to the general population. Clinicians need to consider psoriasis in MC patients with skin lesions.Keywords: microscopic colitis, psoriasis, epidemiology

Background: Patients treated with systemics for moderate‐to‐severe psoriasis have increased risk of cardiovascular disease (CVD). However, to the best of our knowledge, there are no data on the association between clinical disease activity and future cardiovascular events in this population. Such data could help identify patients at increased CVD risk and inform the potential for CVD prevention with effective psoriasis treatment. Objective: To estimate the association between the Psoriasis Area and Severity Index (PASI) and cardiovascular events defined as hospitalization for CVD and cardiovascular death. Methods: We linked prospectively collected data on PASI and CVD risk factors to population‐based administrative data on hospitalizations and causes of death. We estimated the association between PASI and cardiovascular events using Cox proportional hazard models with PASI and Framingham 10‐year cardiovascular risk as time‐varying covariates. Results: A total of 767 patients with 6264 PASI scores were included. After adjusting for 10‐year cardiovascular risk and prior CVD, a one‐point increase in PASI was associated with a hazard ratio of 1.04 (95% CI: 1.01–1.07) for cardiovascular events. The findings were robust in sensitivity analyses. Conclusion: PASI is an independent marker for future cardiovascular events in patients with moderate‐to‐severe psoriasis. [ABSTRACT FROM AUTHOR]

Background: APPRECIATE is a multinational, observational, retrospective, cross‐sectional study in patients treated for psoriasis with apremilast, an oral phosphodiesterase 4 inhibitor. Objectives: To describe the characteristics of patients with psoriasis treated with apremilast in the clinical setting, to evaluate real‐world outcomes of psoriasis treatment with apremilast and to better understand the perspectives of patients and physicians on treatment outcomes. Methods: In six European countries, patients with chronic plaque psoriasis treated in clinical practice who could be contacted 6 (±1) months after apremilast initiation were enrolled. Patient characteristics, Dermatology Life Quality Index (DLQI) and Psoriasis Area and Severity Index (PASI) were obtained from medical records when available. Outcomes were evaluated using patient/physician questionnaires. Results: In 480 patients at treatment initiation, mean [median; 95% confidence interval (CI)] PASI and DLQI scores were 12.5 (10.7; 11.6–13.4) and 13.4 (13.0; 11.4–14.2), respectively. At 6 (±1) months, 72.3% of patients (n = 347) continued apremilast treatment [discontinuations: lack of efficacy (13.5%), safety (11.7%), other (2.5%)]. In patients continuing treatment, 48.6% achieved a ≥75% reduction in PASI score; mean (95% CI) DLQI score was 5.7 (4.5–6.9), and mean (SD) Patient Benefit Index score was 2.8 (1.2). Physicians perceived clinical improvement in 75.6% of patients. Physicians' perspective on overall success of apremilast in meeting expectations correlated with patients' perception of treatment benefit (r = 0.691). Most commonly reported adverse events (>5% of patients) were diarrhoea, nausea and headache. Conclusions: Patients in APPRECIATE reported high disease burden despite more moderate skin involvement than those who enrolled in clinical trials of apremilast. Findings from APPRECIATE demonstrate the real‐world value of apremilast for psoriasis treatment, as 7 of 10 patients continued therapy and showed notable improvement in disease severity and quality of life 6 (±1) months after apremilast initiation. Linked Commentary: P. Gisondi et al. J Eur Acad Dermatol Venereol 2021; 35: 13. https://doi.org/10.1111/jdv.17067. [ABSTRACT FROM AUTHOR]

Background: Psoriatic arthritis (PsA) develops in ~30% of patients with psoriasis. The diagnosis of PsA is challenging, and there are no reliable molecular markers in clinical use. MicroRNAs are short non‐coding regulatory RNAs, which can be actively packaged into extracellular vesicles (EVs) and secreted to the circulation. Objectives: To explore whether plasma‐derived EV microRNAs may serve as biomarkers for PsA in patients with psoriasis. Methods: Plasma samples were obtained from patients with cutaneous‐only psoriasis (PsC) and patients with psoriasis and PsA. Plasma EVs were isolated using miRCURY™ Exosome Isolation Kit. RNA sequencing was used to identify differentially expressed EV miRNAs in the discovery phase (PsC, n = 15; PsA, n = 14). In the validation phase (PsC, n = 29; PsA, n = 28), 41 selected miRNAs were analysed in plasma EVs by qPCR. The association of the identified miRNAs with PsA was assessed by logistic regression analysis. Results: RNA sequencing identified 19 plasma EV miRNAs with significantly different levels between PsA and PsC in the discovery cohort. Significantly lower levels of plasma EV let‐7b‐5p and miR‐30e‐5p in PsA vs. PsC were confirmed in the validation cohort, and their decreased levels were found to be associated with the presence of PsA. ROC analysis revealed an AUC of 0.68 (95% CI 0.53–0.83) for let‐7b‐5p and 0.69 (95% CI 0.55–0.84) for miR‐30e‐5p. Conclusions: Circulating EV microRNA levels are altered in patients with PsA as compared with PsC. Findings of this exploratory study suggest that circulating EV microRNAs may serve as biomarkers for arthritis in psoriasis patients. [ABSTRACT FROM AUTHOR]

Background: The advent of biosimilars may render etanercept (ETN) and adalimumab (ADA) viable alternatives to methotrexate (MTX) as first‐line systemics in psoriasis. However, real‐world relative effectiveness data comparing ADA and ETN to MTX are limited. Objective: To estimate the relative effectiveness of ADA and ETN compared to MTX. Methods: We analysed data from DermaReg, a regional register in Stockholm, Sweden, to estimate drug survival and mean Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) during maintenance treatment. Results: A total of 524 patients initiated 727 treatment episodes with ADA, ETN or MTX. After adjusting for confounders, patients treated with ADA had better drug survival (HR: 0.67; P = 0.003), lower mean PASI (−2.0; P < 0.001) and lower mean DLQI (−0.9; P < 0.001) during maintenance treatment compared to patients treated with MTX. The results for ETN compared to MTX were mixed. After adjusting for confounding, there was no significant difference in drug survival (HR 1.23; P = 0.082), but patients on ETN had lower mean PASI (−0.7; P = 0.006) during maintenance treatment. Conclusion: Adalimumab is superior to MTX in clinical practice whereas the relative effectiveness between ETN and MTX is less clear. This study also highlights the importance of appropriate confounding control in effectiveness analysis. [ABSTRACT FROM AUTHOR]