INTRODUCTION: Real-world data on the effectiveness of upadacitinib for inflammatory bowel disease (IBD) are limited. To assess upadacitinib persistence, effectiveness, and safety in a real-world scenario. METHODS: Retrospective multicenter study of patients with IBD who received upadacitinib before 31st December 2022 and at least 12 weeks before the recruitment date. Clinical effectiveness was assessed based on partial Mayo score for ulcerative colitis (UC) and Harvey–Bradshaw index for Crohn's disease (CD). RESULTS: We included 100 patients (68 with CD, and 32 with UC). Patients had previously received a median of 4 advanced therapies. Twenty-three discontinued the treatment (median follow-up 7.6 months). CD (vs UC) (hazard ratio 3.7; 95% confidence interval [CI]: 1.04–12.9) and age below 40 years at upadacitinib initiation (hazard ratio 2.4; 95% CI: 1.0–5.8) were associated with treatment discontinuation in multivariable analysis. Clinical remission for IBD was achieved in 59% of patients at week 8, 64% at week 12, and 42% at week 52. The proportion of patients with UC previously exposed to tofacitinib (n = 25) who achieved clinical remission was 78% at week 12, and 50% at week 52. Factors associated with clinical remission at week 12 were UC diagnosis (odds ratio [OR] 4.6; 95% CI: 1.3–17), mild or moderate activity at baseline (OR 8; 95% CI: 1.1–56), and not smoking (OR 4.4; 95% CI: 1.5–13). Dose escalation recaptured remission in 60% of patients with relapse. Eighty percent of patients with active immune-mediated diseases or extraintestinal manifestations improved with upadacitinib. Forty-three patients reported adverse events, 11 of them serious. DISCUSSION: Upadacitinib is effective and safe for treating patients with highly refractory IBD, even in previously treated with Janus kinase inhibitors.

Malondialdehyde (MDA) is a naturally occurring organic compound produced as a byproduct of lipid peroxidation. It serves as one of the most widely recognized biomarkers for oxidative stress. Elevated levels of MDA have been observed in patients with inflammatory bowel disease (IBD), suggesting its involvement in the pathogenesis and progression of the disease. In this study, we analyzed MDA levels within a well-characterized and extensive cohort of IBD patients. Our objective was to investigate the association between MDA levels and disease characteristics in this population. This is a cross-sectional study that encompassed 197 patients with IBD. Multivariable linear regression analysis was performed to study the relationship between disease characteristics and circulating MDA. MDA was significantly associated with male sex in IBD patients but not with other demographic characteristics or classic cardiovascular risk factors. Regarding disease features such as phenotype or activity indices, their relationship with MDA was scarce. Several lipid profile molecules showed a significant association with MDA levels after multivariable analysis. Similarly, the liver fibrosis-4 index and hepatic elastography values were significantly related to higher MDA levels after adjusting for covariates. In conclusion, the sources of elevated MDA in IBD are primarily linked to lipid profile abnormalities and liver disease.

The addition of carotid ultrasound into cardiovascular (CV) risk scores has been found to be effective in identifying patients with chronic inflammatory diseases at high-CV risk. We aimed to determine if its use would facilitate the reclassification of patients with inflammatory bowel disease (IBD) into the very high-CV-risk category and whether this may be related to disease features. In this cross-sectional study encompassing 186 IBD patients and 175 controls, Systematic Coronary Risk Evaluation (SCORE), disease activity measurements, and the presence of carotid plaques by ultrasonography were assessed. Reclassification was compared between patients and controls. A multivariable regression analysis was performed to evaluate if the risk of reclassification could be explained by disease-related features and to assess the influence of traditional CV risk factors on this reclassification. After evaluation of carotid ultrasound, a significantly higher frequency of reclassification was found in patients with IBD compared to controls (35% vs. 24%, p = 0.030). When this analysis was performed only on subjects included in the SCORE low-CV-risk category, 21% IBD patients compared to 11% controls (p = 0.034) were reclassified into the very high-CV-risk category. Disease-related data, including disease activity, were not associated with reclassification after fully multivariable regression analysis. Traditional CV risk factors showed a similar influence over reclassification in patients and controls. However, LDL-cholesterol disclosed a higher effect in controls compared to patients (beta coef. 1.03 (95%CI 1.02–1.04) vs. 1.01 (95%CI 1.00–1.02), interaction p = 0.035) after adjustment for confounders. In conclusion, carotid plaque assessment is useful to identify high-CV risk IBD patients.

Background. Insulin resistance (IR) has been linked to inflammatory states. The aim of this study was to determine whether IR is increased in a cohort of inflammatory bowel disease (IBD) patients with low disease activity. We additionally intended to establish which factors were the determinants of IR in this population, including the presence of nonalcoholic fatty liver disease (NAFLD). Methods. Cross-sectional study encompassing 151 IBD patients and 174 non-diabetic controls. Insulin and C-peptide serum levels and IR and beta cell function (%B) indices based on homoeostatic model assessment (HOMA2) were assessed in patients and controls. Liver stiffness as measured by transient elastography, and the presence of NAFLD detected via ultrasound were additionally assessed. A multivariable regression analysis was performed to evaluate the differences in IR indexes between patients and controls, and to determine which predictor factors were associated with IR in IBD patients. Results. Neither HOMA2-IR (beta coef. −0.26 {95%CI −0.64–0.13}, p = 0.19) nor HOMA2-%B (beta coef. 15 {95%CI −14–44}, p = 0.31) indexes differed between patients and controls after fully multivariable analysis. Among classic IR risk factors, obesity, abdominal circumference, and triglycerides significantly and positively correlated with IR indexes in IBD patients. However, most features related to IBD, such as disease patterns, disease activity, and inflammatory markers, were not associated with IR. The presence of NAFLD was independently and significantly associated with beta cell dysfunction in patients with IBD (HOMA2—B grade 4, 251 ± 40 vs. grade 1, 107 ± 37, p = <0.001). Conclusions. IR is not increased in IBD patients with low disease activity compared to controls. However, the presence of NAFLD favors the development of IR in patients with IBD.

The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and the systemic immune-inflammatory index (SIRI, neutrophils × monocytes/lymphocytes) have been identified as potential inflammatory biomarkers. In this work we aimed to analyze whether the hematological composite scores differ between inflammatory bowel disease (IBD) patients and healthy controls, and if they are related to disease activity. A total of 197 IBD patients—130 Crohn’s (CD) disease and 67 ulcerative colitis (UC)—and 208 age- and sex-matched healthy controls were enrolled. C-reactive protein and fecal calprotectin were assessed. Multivariable linear regression analysis was executed. After adjustment, NLR and PLR, but not SIRI and MLR, were significantly higher in IBD patients compared to controls. C-reactive protein and SIRI and NLR were correlated in IBD patients. However, fecal calprotectin was not related to any of these blood scores. Furthermore, disease activity parameters were not associated with any of the blood composite scores in both CD and UC patients. In conclusion, NLR and PLR, but not SIRI and MLR, are independently higher in IBD patients compared to controls. However, the four hematological scores are not related to disease activity in either CD or UC patients. Based on these results, blood-based inflammatory scores may not serve as subrogated biomarkers of disease activity in IBD.