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Background: The skin–gut axis, characterized by bidirectional communication between the skin and gut, plays a crucial role in the pathogenesis of psoriasis and inflammatory bowel diseases (IBD). Objectives: We aimed to explore the association between psoriasis and IBD and identify predictors associated with IBD development among patients with psoriasis. Design: Retrospective cohort study. Methods: A retrospective study which utilized an electronic database from the Meuhedet Health Maintenance Organization (MHMO) in Israel. Psoriasis was categorized as severe if any systemic agent or phototherapy was administered. Univariate and multivariate logistic regressions were used to identify specific predictors for IBD, with adjustments made for potential confounders. The study received approval from the Ethical Committee of the MHMO. Results: In total, 61,003 adult patients who were diagnosed with psoriasis between 2000 and 2022 were included. Among them, 1495/61,003 patients (2.4%) were diagnosed with IBD, as compared to 3834/244,012 patients (1.6%) in the non-psoriasis group [adjusted odds ratio (OR): 1.47; 95% confidence interval (CI): 1.37–1.56; p < 0.001]. Increased age (OR: 1.01; 95% CI: 1.01–1.02; p < 0.001), male gender (OR: 1.22; 95% CI: 1.03–1.45; p = 0.024), and Jewish ethnicity (OR: 2.5; 95% CI: 1.2–4.1; p < 0.001) were identified as significant risk factors for IBD. Spondyloarthropathies, including psoriatic arthritis (OR: 2.27; 95% CI: 1.86–2.77; p < 0.001) and ankylosing spondylitis (OR: 2.82; 95% CI: 1.5–5.32; p < 0.05), were associated with a higher prevalence of IBD. Furthermore, severe psoriasis was significantly associated with a higher likelihood of IBD, compared to mild psoriasis (OR: 16.03; 95% CI: 11.02–23.34; p < 0.001). Conclusion: A significant association between psoriasis and IBD was demonstrated, including its subtypes: Crohn's disease and ulcerative colitis. Moreover, such association may depend on psoriasis severity as determined by the treatment used. This association warrants further investigation and implies a potential need for closer monitoring of patients with severe psoriasis. Plain language summary: Association between psoriatic disease severity and risk of inflammatory bowel diseases 1- Gut and skin barrier play an integral role in psoriasis and inflammatory bowel disease (IBD) development. 2- Shared genetic and environmental factors could explain the association between both diseases. 3- We report increased association between psoriasis and IBD, a relationship that is more pronounced in patients with severe psoriasis. 4- Patients with spondyloarthritis related diseases have a stronger association with IBD. [ABSTRACT FROM AUTHOR]

Objective The association between chronic inflammatory conditions and cardiovascular disease is well established. Considering FMF, few studies exist investigating the risk of ischaemic heart disease, and none address the risk of stroke. We aimed to evaluate the incidence and risk for stroke in FMF patients compared with the general population. Methods A retrospective cohort study using the electronic database of Clalit Health Services (CHS), the largest health organization in Israel. All FMF patients diagnosed between 2000 and 2016 were included and matched with control according to age, gender and place of residence. Follow-up continued until the first diagnosis of stroke or death. The incidence of stroke was compared between the groups using univariate and multivariate models adjusting for cardiovascular risk-factors. Results A total of 9769 FMF patients and a similar number of controls were followed up for a median period of 12.5 years. The mean age at the beginning of the follow-up was 25.7 years. In total, 208 FMF patients were diagnosed with stroke compared with 148 controls, resulting in an incidence rate (per 10 000 persons-years) of 19.8 (95% CI 17.2, 22.7) and 13.9 (95% CI 11.8, 16.4), respectively, and a crude HR of 1.42 (95% CI 1.15–1.76; P  < 0.001). In a multivariate analysis, FMF patients who developed amyloidosis with related or non-related renal failure demonstrated significant stroke risk (HR = 2.16; 95% CI 1.38, 3.38; P  < 0.001), as well as for those who did not develop these complications (HR = 1.32; 95% CI 1.04, 1.67; P  < 0.05). Conclusion FMF patients are at increased risk for stroke regardless of known complications. [ABSTRACT FROM AUTHOR]

Introduction: Active metabolite of vitamin D has neuro-immunomodulatory and neuroprotective properties. However, there is still a debate about the potential association between low serum levels of hydroxy-vitamin D and increased risk for dementia. Objectives: To determine an association between hypovitaminosis D and dementia for different 25-hydroxyvitamin-D (25(OH)D) serum level cutoffs. Methods: Patients were identified utilizing the database of Clalit Health Services (CHS), the largest healthcare provider in Israel. For each subject, all available values of 25(OH)D during the study period, which lasted from 2002 to 2019, were obtained. Rates of dementia were compared across different cutoffs of 25(OH)D levels. Results: Cohort included 4278 patients, of whom 2454 (57%) were women. The mean age at the beginning of follow-up was 53 (±17). During the 17-year study period, a total of 133 patients (3%) were diagnosed with dementia. In a fully adjusted multivariate analysis, the risk for dementia was almost 2-fold higher in patients with an average of vitamin D insufficiency (<75 nmol/l) measurements (OR = 1.8, 95% C.I. = 1.0-3.2) compared to reference values (≥75 nmol/l). Patients with vitamin D deficiency (<50 nmol/l) demonstrated higher rates of dementia (OR = 2.6, 95% C.I. = 1.4-4.8). In our cohort, patients were diagnosed with dementia at a younger age in the deficiency (77 vs. 81 P -value = 0.05) and the insufficiency groups (77 vs. 81 P -value = 0.05) compared to the reference values (≥75 nmol/l). Conclusion: Insufficient levels of vitamin D are associated with dementia. Dementia is diagnosed at a younger age in patients with insufficient and deficient vitamin D levels. [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy and safety of ABBV‐3373, a novel antibody–drug conjugate (ADC) composed of the anti–tumor necrosis factor (anti‐TNF) monoclonal antibody adalimumab linked to a glucocorticoid receptor modulator (GRM), compared to adalimumab, in patients with rheumatoid arthritis (RA). Methods: In this randomized, double‐blind, active‐controlled, proof‐of‐concept trial (ClinicalTrials.gov identifier: NCT03823391), adults with moderate‐to‐severe RA receiving background methotrexate were administered intravenously (IV) ABBV‐3373 100 mg every other week for 12 weeks, followed by placebo for 12 weeks, or subcutaneous adalimumab 80 mg every other week for 24 weeks. The primary end point was change from baseline in the Disease Activity Score in 28 joints using C‐reactive protein (DAS28‐CRP) at week 12, with 2 prespecified primary comparisons of ABBV‐3373 versus historical adalimumab (80 mg every other week or equivalent dose) and versus combined in‐trial/historical adalimumab. Secondary end points included change from baseline in the Clinical Disease Activity Index, Simplified Disease Activity Index, and DAS28 using erythrocyte sedimentation rate, as well as the proportion of patients achieving a DAS28‐CRP of ≤3.2 and the American College of Rheumatology 50% improvement criteria. Results: Forty‐eight patients were randomized to receive either ABBV‐3373 (n = 31) or adalimumab (n = 17). At week 12, ABBV‐3373 demonstrated a reduction in DAS28‐CRP compared to historical adalimumab (−2.65 versus −2.13; P = 0.022) and compared to combined in‐trial/historical adalimumab (−2.65 versus −2.29; probability 89.9%), with numerically greater improvement than in‐trial adalimumab (−2.51). For secondary end points, greater efficacy was observed with ABBV‐3373 compared to historical adalimumab; ABBV‐3373 was predicted with 79.3–99.5% probability to be more effective than adalimumab based on combined in‐trial/historical adalimumab data. Of the ABBV‐3373–treated patients who achieved DAS28‐CRP ≤3.2 at week 12, 70.6% maintained this response at week 24 despite switching to placebo. Four serious adverse events (SAEs) were reported with ABBV‐3373 (noncardiac chest pain, pneumonia, upper respiratory tract infection, and anaphylactic shock) and 2 SAEs with adalimumab (breast abscess and bronchitis). After increasing the duration of IV ABBV‐3373 administration from 3 minutes to 15–30 minutes, no similar events of anaphylactic shock were reported. Conclusion: Data from this proof‐of‐concept trial support the continued development of a TNF–GRM ADC for the treatment of RA, with the potential to achieve superior outcomes compared to currently available therapies. [ABSTRACT FROM AUTHOR]