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Background: The emergence of new treatments the inflammatory bowel diseases (IBD) raised questions regarding the role of older agents, namely thiopurines., Aims: To clarify the benefits of combination treatment with thiopurines on Crohn's disease (CD) patients in the maintenance phase of infliximab., Methods: In this analysis of the 2-year prospective multicentric DIRECT study, patients were assessed in terms of clinical activity, faecal calprotectin (FC), C-reactive protein (CRP), and infliximab pharmacokinetics. A composite outcome based on clinical- and drug-related items was used to define treatment failure., Results: The study included 172 patients; of these, 35.5 % were treated with combination treatment. Overall, 18 % of patients achieved the composite outcome, without statistically significant differences between patients on monotherapy and on combination treatment (21.6% vs 11.5 %, p = 0.098). Median CRP, FC, and infliximab pharmacokinetic parameters were similar in both groups. However, in the sub-analysis by infliximab treatment duration, in patients treated for less than 12 months, the composite outcome was reached in fewer patients in the combination group than in the monotherapy group (7.1% vs 47.1 %, p = 0.021)., Conclusion: In CD patients in maintenance treatment with infliximab, combination treatment does not seem to have benefits over infliximab monotherapy beyond 12 months of treatment duration., Competing Interests: Conflict of interest PS served as speaker for Janssen and received Congress support from Janssen, Abbvie, Dr. Falk, Norgine and Pfizer. IR reports personal fees and/or non-financial support from Faes Pharma, Ferring, Pharmakern, Janssen and Takeda, outside the submitted work. She also reports research grants from Abbvie and Ferring, outside the submitted work. HTS served as speaker for Janssen and received Congress support from Abbvie, Ferring, Janssen, Pfizer, Takeda, Tillots, Dr. Falk and Biogen. FM served as a speaker and received honoraria from Abbvie, Biogen, Falk, Ferring, Hospira, Janssen, Laboratórios Vitória, Lilly, Pfizer, Merck Sharp & Dohme, Sandoz, Takeda, UCB and Vifor. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Subclinical intestinal inflammation is common in Crohn's disease (CD). We aimed to explore its impact in the disease progression of infliximab-treated patients and the usefulness of fecal calprotectin (FC) and C-reactive protein (CRP) as surrogate minimally invasive biomarkers. The registry-based, prospective, observational, multicenter DIRECT (study to investigate the correlation of fecal calprotectin with serum Drug levels and development of an antI-dRug antibodiEs among adult patients with inflammatory bowel disease reCeiving anti-TNF-alfa treatment or vedoluzimab treatment) study followed infliximab-treated CD patients for 2 years in a tertiary care setting. Persistent inflammation definition was based on FC (>150 μg/g, >250 μg/g, or >350 μg/g) or serum CRP (>3 μg/mL) concentrations over 2 consecutive or at least 3 visits. Patients were categorized according to a composite outcome reflecting disease progression that incorporated surgery; hospitalizations; new fistulae, abscess, or stricture; and treatment escalation. Of 322 DIRECT study patients, 180 asymptomatic, infliximab treated on maintenance regimen were included in the analysis. Patients developing the composite endpoint (n = 96) presented higher median levels of FC (205 [interquartile range, 98–515] μg/g; P =.045) but not of CRP (2.50 [interquartile range, 0.80–6.00] μg/mL; P =.895). Biomarker-defined persistent subclinical inflammation prevalence ranged from 24% to 81%. Considering FC >250 μg/g in 2 consecutive visits, prevalence was 50%, odds of achieving the endpoint were increased 3-fold (odds ratio, 2.996 [95% confidence interval, 1.557–5.776]), and time-to-outcome occurrence was significantly lower among subjects with persistent inflammation (median time: 11 months). Both clinical-related and treatment-related components were significantly associated with persistent inflammation. Definitions based on CRP >3 μg/mL, FC >150 μg/g, FC >350 μg/g, double biomarkers (FC >250 μg/g and/or CRP >3 μg/mL), or more visits did not improve predictive ability. Persistent inflammation, defined simply and readily by FC >250 μg/g over 2 consecutive visits, was associated with a significantly higher risk and shorter time to occurrence of a composite outcome reflecting disease progression in asymptomatic infliximab-treated CD patients. [ABSTRACT FROM AUTHOR]

Background: Suppressor of Tumorigenicity 2 (ST2) is an IL33 receptor detected in the mucosa and serum of ulcerative colitis (UC) patients. We evaluated soluble ST2 (sST2) as a surrogate biomarker of disease outcome and therapeutic response, in moderate-to-severe UC patients treated with golimumab. Methods: We conducted an open-label single-arm multicentre prospective study. At screening/baseline, week 6 (W6) and week 16 (W16), clinical and endoscopic activity (total Mayo score), histologic activity (Geboes index) and biomarkers were evaluated. Results: From 38 patients, 34 (89.5%) completed W6 and 29 (76.3%) completed W16. Mean age (±SD) was 34.6 ± 12.6 years; 55.9% were female. At W16, 62.1% achieved clinical response. Patients with endoscopic activity at W6 (n = 20) had higher baseline sST2 (median, 24.5 versus 18.7 ng/ml, p = 0.026) and no decrease from baseline (median change, 0.8 versus −2.7, p = 0.029). At W6, sST2 levels correlated with endoscopic activity (rs = 0.45, p = 0.007) but not with histological activity (rs = 0.25, p = 0.151). The best cut-offs for endoscopic activity were sST2 = 16.9 ng/ml (sensitivity = 85%; specificity = 71%) and faecal calprotectin (FC) = 353 μg/g (sensitivity = 90%, specificity = 67%). Patients with histological activity at W6 (n = 27) had higher baseline ST2 levels (median, 23.0 versus 13.7 ng/ml, p = 0.035). sST2 did not correlate with FC or serum C-reactive protein. FC levels correlated with histological activity and baseline FC were higher when Geboes ⩾3.1 at W6. Conclusions: sST2 may be a surrogate biomarker of UC activity and therapeutic response as it correlates with endoscopic and clinical activity at W6 of golimumab treatment, and subjects with endoscopic and histological activity at W6 had higher baseline ST2 levels. [ABSTRACT FROM AUTHOR]