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Background: Data on predictors of complicated ulcerative colitis (UC) course from unselected populations cohorts are scarce. We aimed to utilize a nationwide cohort to explore predictors at diagnosis of disease course in children and adults with UC., Methods: Data of patients diagnosed with UC since 2005 were retrieved from the nationwide epi-IIRN cohort. Complicated disease course was defined as colectomy, steroid-dependency, or the need for biologic drugs. Hierarchical clustering categorized disease severity at diagnosis based on complete blood count, albumin, C-reactive protein and erythrocyte sedimentation rate (ESR), analyzed together., Results: A total of 13 471 patients with UC (1427 [11%] pediatric-onset) including 103 212 person-years of follow-up were included. Complicated disease course was recorded in 2829 (21%) patients: 1052 (7.9%) escalated to biologics, 1357 (10%) experienced steroid-dependency, and 420 (3.1%) underwent colectomy. Probabilities of complicated disease course at 1 and 5 years from diagnosis were higher in pediatric-onset (11% and 32%, respectively) than adult-onset disease (4% and 16%; P < .001). In a Cox multivariate model, complicated course was predicted by induction therapy with steroids (hazard ratio [HR], 1.5; 95% CI, 1.2-2.0), extraintestinal manifestations (HR, 1.3; 95% CI, 1.03-1.5) and the disease severity clusters of blood tests (HR, 1.8; 95% CI, 1.01-3.1), while induction therapy with enemas (HR, 0.6; 95% CI, 0.5-0.7) and older age (HR, 0.99; 95% CI, 0.98-0.99) were associated with noncomplicated course., Conclusion: In this nationwide cohort, the probability of complicated disease course during the first 5 years from diagnosis was 32% in pediatric-onset and 16% in adults with UC and was associated with more severe clusters of routinely collected laboratory tests, younger age at diagnosis, extraintestinal manifestations, and type of induction therapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: In this nationwide study, our objective was to compare the durability of first-line biologics in ulcerative colitis (UC), categorized into monotherapy and combotherapy with immunomodulators., Methods: We utilized data from the nationwide epi-IIRN cohort from 2005 to 2020. Durability was defined as consistent treatment without surgery. Comparisons were based on stringent propensity score-matching., Results: We included 15 111 patients with UC, of whom 2322 (15%) received biologics, with a median follow-up of 7.0 years (interquartile range, 3.8-11.0). The durability rate was similar between pediatric-onset and adults after 1 and 5 years from initiation of treatment (72% and 43% vs 71% and 43%, respectively; P = .8). Durability of adalimumab vs infliximab after 1 or 5 years was similar, whether prescribed as monotherapy (65%/46% vs 63%/33%, respectively; n = 182 matched pairs, P = .3) or combotherapy (78%/56% vs 91%/58%, respectively; n = 46 matched pairs, P = .4). Durability of infliximab was higher as combotherapy (85%/50%) vs monotherapy (69%/42%; n = 174 matched pairs, P = .007), while it was similar for adalimumab (80%/52% vs 74%/52%; n = 53 matched pairs, P = .4). The durability rate was similar for vedolizumab monotherapy (77%/56%) compared with adalimumab monotherapy (69%/52%; n = 125 matched patients, P = .1), and infliximab monotherapy (73%/55% vs 62%/44%; n = 78 matched patients, P = .1). However, combotherapy of antitumor necrosis factors (TNFs) had longer durability than vedolizumab (85%/50% vs 75%/43%, respectively; n = 131 matched pairs, P = .02)., Conclusion: After 5 years of treatment, 43% of the patients with UC sustained their first biologic, with similar durability in pediatric and adult-onset onset disease. Anti-TNFs had similar durability to vedolizumab and superior durability when prescribed as combotherapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background and Aims: We conducted this nationwide study to evaluate the association between peripheral blood eosinophilia (PBE) and long-term outcomes in children and adults with inflammatory bowel diseases (IBDs)., Methods: Data from the Epidemiology Group of the Israeli IBD Research Nucleus (epi-IIRN) cohort, a validated population-based IBD database, included patients diagnosed between 2005 and 2020, who had an eosinophil count recorded at diagnosis, and non-IBD controls. PBE was defined as an eosinophil count of >0.5 × 109/L. Severe disease course was defined as corticosteroid dependency, use of ≥2 biologics from different classes, or surgery. Time-to-outcomes, including severe disease course, was determined by Cox proportional hazard models., Results: This study included 28 133 patients (15 943 Crohn's disease [CD] and 12 190 ulcerative colitis [UC]) and 28 724 non-IBD controls. The prevalence of PBE was 13% in the IBD group and 5% in the control group (p < 0.001). PBE was more prevalent in UC (16.1%) compared to CD (10.6%, odds ratio [OR] = 1.52, 95% confidence interval [CI], 1.42-1.63; p < 0.001) and in pediatric-onset (23.5%) compared to adult-onset (11%) IBD (OR = 2.14, 95% CI, 1.97-2.31; p < 0.001). In a multivariate analysis, PBE was a predictor of severe disease course in IBD (hazard ratio [HR] = 1.49, 95% CI, 1.38-1.62, p < 0.001). PBE also predicted time-to-hospitalization (HR = 1.24, 95% CI, 1.19-1.30), use of corticosteroids (HR = 1.32, 95% CI, 1.28-1.36), corticosteroid dependency (HR = 1.37, 95% CI, 1.31-1.43), and need for biologics (HR = 1.27, 95% CI, 1.21-1.33)., Conclusions: In this largest nationwide study, PBE predicted severe IBD course. These findings support the use of PBE as a marker of adverse outcomes of IBD and as a potential target for future therapies., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Urinary tract infections (UTIs) often prompt empiric outpatient antibiotic prescriptions, risking mismatches. This study evaluates the impact of "UTI Smart-Set" (UTIS), an AI-driven decision-support tool, on prescribing patterns and mismatches in a large outpatient organization. UTIS integrates machine learning forecasts of antibiotic resistance, patient data, and guidelines into a user-friendly order set for UTI management. From 6/1/2021-8/31/2022, 171,010 UTI diagnoses were recorded, with UTIS used in 75,630 cases involving antibiotic prescriptions. Overall acceptance rate of UTIS recommendations was 66.0%. Among 19,287 cases with urine cultures, antibiotic mismatch rate was significantly lower when UTIS recommendations were followed (8.9% vs. 14.2%, p < 0.0001). Among women over 18, mismatch rate was 47.5% lower, and among women over 50, 55.6% lower (p < 0.001). Additionally, an overall reduction of 80.5% in ciprofloxacin usage (6.4% vs 32.9%, p < 0.0001) was observed. UTIS improved prescribing accuracy, reduced mismatches, and minimized quinolone use, highlighting AI's potential for personalized infection management., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Since data on predictors of complicated Crohn's disease (CD) from unselected populations are scarce, we aimed to utilize a large nationwide cohort, the epi-IIRN, to explore predictors of disease course in children and adults with CD., Methods: Data of patients with CD were retrieved from Israel's 4 health maintenance organizations, whose records cover 98% of the population (2005-2020). Time-to-event modeled a complicated disease course, defined as CD-related surgery, steroid-dependency, or the need for >1 class of biologics. Hierarchical clustering categorized disease severity at diagnosis based on available laboratory results., Results: A total of 16 659 patients (2999 [18%] pediatric-onset) with 121 695 person-years of follow-up were included; 3761 (23%) had a complicated course (750 [4.5%] switched to a second biologic class, 1547 [9.3%] steroid-dependency, 1463 [8.8%] CD-related surgery). Complicated disease was more common in pediatric- than adult-onset disease (26% vs 22%, odds ratio, 1.3; 95% confidence interval [CI], 1.2-1.4). In a Cox multivariate model, complicated disease was predicted by induction therapy with biologics (hazard ratio [HR], 2.1; 95% CI, 1.2-3.6) and severity of laboratory tests at diagnosis (HR, 1.7; 95% CI, 1.2-2.2), while high socioeconomic status was protective (HR, 0.94; 95% CI, 0.91-0.96). In children, laboratory tests predicted disease course (HR, 1.8; 95% CI, 1.2-2.5), as well as malnutrition (median BMI Z score -0.41; 95% CI, -1.42 to 0.43 in complicated disease vs -0.24; 95% CI, -1.23 to 0.63] in favorable disease; P < .001)., Conclusions: In this nationwide cohort, CD course was complicated in one-fourth of patients, predicted by laboratory tests, type of induction therapy, socioeconomic status, in addition to malnutrition in children., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Both corticosteroids and exclusive enteral nutrition (EEN) have been used as induction therapy in children with Crohn's disease (CD)., Aim: To compare in a nationwide study the long-term outcomes of children with CD receiving either EEN or corticosteroids as induction therapy., Methods: We retrieved data of all children diagnosed with CD (2005-2020) from the epi-IIRN cohort covering 98% of the Israeli population. The primary outcome was time to complicated disease course (i.e., surgery, steroid-dependency, or at least 2 biologic class). Patients were matched individually utilising propensity score adjustments., Results: We included 410 children treated with EEN and 375 with corticosteroids without other treatments (median follow-up, 4.73 [IQR: 2.2-7.2] years [1433 patient-years]). For 274 matched children, the probability of a complicated course was higher with corticosteroids than EEN at 0.5, 3 and 5 years (14% vs. 4%, 42% vs. 27% and 54% vs. 41%, respectively, p = 0.0066), despite similar use of biologics. Steroid-dependency (10% vs. 2%, 15% vs. 3%, and 20% vs. 5%, respectively, p = 0.00018), and hospitalisations (20% vs. 11%, 37% vs. 26%, and 55% vs. 38%, respectively, p = 0.002) were higher with corticosteroids. During follow-up, children receiving corticosteroids as induction treatment were more often further exposed to corticosteroids, and those on EEN were more often further exposed to nutritional treatment (p < 0.001). Induction with EEN had no advantage over corticosteroids regarding survival probability of surgeries, biologic use and growth., Conclusions: EEN in paediatric CD is associated with lower long-term risks of corticosteroid dependency and hospitalisation than corticosteroids. These results may lend support to favouring nutritional therapy in paediatric CD., (© 2024 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background & Aims: In this nationwide study, we explored whether early initiation of biologics is associated with improved outcomes in children and adults with Crohn's disease (CD) and ulcerative colitis (UC)., Methods: All patients diagnosed with CD or UC in Israel (2005-2020) were included in the Epidemiology Group of the Israeli Inflammatory Bowel Disease Research Nucleus cohort, encompassing 98% of the population. We compared disease duration at biologics initiation (ie, 0-3 months, >3-12 months, >1-2 years, and >2-3 years) using the cloning, censoring, and weighting by inverse probabilities method to emulate a target trial, adjusting for time-varying confounders and selection bias., Results: Of the 34,375 included patients (of whom 5240 [15%] were children), 7452 of 19,264 (39%) with CD and 2235 of 15,111 (15%) with UC received biologics. In CD, by 10 years postdiagnosis, the probability of CD-related surgery decreased gradually but modestly with earlier initiation of biologics; a significant difference was noted between >2-3 years (31%) and 0-3 months (18%; P = .02; number needed to treat, 7.7), whereas there was no difference between the 0-3-month and >3-12-month periods. The 10-year probability of steroid dependency for the 0-3-month period (19%) differed both from the >2-3-year (31%; P < .001) and 1-2-year periods (37%; P < .001). In UC, no significant differences in colectomy or steroid dependency rates were observed between the treatment initiation periods. Similar trends were noted in the pediatric population., Conclusions: Very early initiation of biologics was not associated with some outcomes except for a modest risk reduction of surgery and steroid dependency for CD, which requires confirmation in future studies. In UC, early introduction of biologics was not associated with reduced risk of colectomy or steroid dependency., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Data regarding patients with ulcerative colitis (UC) not receiving maintenance treatment are scarce. In this nationwide study, we aimed to explore the frequency and long-term outcomes of untreated patients with UC vs treated patients., Methods: We retrieved data from Israel's Health Maintenance Organizations, covering 98% of the population. No maintenance treatment (NMT) was defined as lack of treatment during the period from 3 to 6 months from diagnosis, allowing at most 3 months for induction treatment., Results: A total of 15 111 patients have been diagnosed with UC since 2005, of whom 4410 (29%) have had NMT, with 36 794 person-years of follow-up. NMT was more likely in adults (31%) and in elderly-onset UC (29%) than in pediatric-onset UC (20%; P < .001) and decreased from 38% in 2005 to 18% in 2019 (P < .001). The probability of remaining without treatment was 78%, 49%, and 37% after 1, 3, and 5 years from diagnosis, respectively. In propensity score-matched analysis of 1080 pairs of treated (93% with 5-aminosalicylic acid) and untreated patients, outcomes were comparable for time to biologics (P = .6), surgery (P = .8), steroid dependency (P = .09), and hospitalizations (P = .2). Multivariable modeling indicated that failing NMT was less likely in adults or elderly-onset patients who received at most rectal therapy or antibiotics as induction therapy., Conclusions: Nowadays, 18% of patients with UC do not receive maintenance therapy, of whom half remain without treatment after 3 years. Matched pairs of patients on NMT and 5-aminosalicylic acid, representing the mildest patients of the latter, had similar outcomes. Prospective studies are needed to further explore the role of NMT in UC., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: In this nationwide study we aimed to compare the durability of the first initiated biologic in Crohn's disease [CD], stratified by monotherapy and combotherapy., Methods: We used data from the epi-IIRN cohort, which includes 98% of the Israeli inflammatory bowel disease population [2005-2020]. Durability was defined as consistent treatment without surgery or added medications [except for combination therapy with thiopurines or methotrexate]. All comparisons were based on stringent propensity-score matching and paired time-to-event analyses., Results: A total of 19 264 patients with CD were included, of whom 7452 [39%] received biologics with a median follow-up of 6.8 years (interquartile range [IQR] 3.6-10.7). Time to biologics decreased gradually from 6.7 years [IQR 2.7-10.4] in 2005 to 0.2 years [0.07-0.23] in 2020. The durability of the first biologic after 1 and 3 years was higher with adalimumab monotherapy [88%/61%] than vedolizumab monotherapy [81%/59%; n = 394 matched patients, p = 0.04] and similar between infliximab monotherapy and vedolizumab monotherapy [65%/43%; n = 182 matched patients, p = 0.1]. Durability was higher in adalimumab monotherapy vs infliximab monotherapy [83%/62% vs 71%/48% at 1/3 years; p <0.001] and it was similar in adalimumab monotherapy vs infliximab combotherapy [87%/63% vs 80%/58%, respectively; p = 0.1]. Durability was higher in combotherapy compared with monotherapy for both infliximab [85%/64% vs 67%/43%, respectively; n = 496 matched pairs, p <0.001], and adalimumab [93%/76% vs 82%/62%, respectively; n = 540 matched pairs, p <0.001]., Conclusion: Durability of the first biologic in CD was highest for adalimumab monotherapy. Combotherapy further increased the durability of adalimumab and infliximab. Unless otherwise indicated, our data may support using anti-tumour necrosis factors [TNFs] as first-line biologics in CD, particularly adalimumab if monotherapy is advised., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Timely access to quality medical care impacts patient outcomes in inflammatory bowel disease (IBD). In a nationwide study from the epidemiology group of the Israeli IBD research nucleus we aimed to assess the impact of residence and socioeconomic status (SES) on disease outcomes., Methods: We utilized data from the 4 health maintenance organizations in Israel, representing 98% of the population. Regions were defined as central, northern and southern; SES was graded from lowest to highest (from 1 to 4) as per Israel Central Bureau of Statistics. The primary outcome was steroid dependency, with secondary outcomes of surgeries and biologic therapy use., Results: A total of 28 216 IBD patients were included: 15 818 (56%) Crohn's disease (CD) and 12 398 (44%) ulcerative colitis; 74%, 12% and 14% resided in central, southern, and northern Israel, respectively (SES 1: 21%, SES 4: 12%). Lower SES was associated with steroid dependency (20% in SES 1 vs 12% in SES 4 in CD; P < .001; and 18% vs 12% in ulcerative colitis; P < .001), and higher surgery rates (12% vs 7%; P < .001, and 1.4% vs 0.7%; P = .115, respectively). There were higher steroid dependency and CD surgery rates in peripheral vs central regions. In multivariable models, both SES and peripheral region were independently associated with poorer outcomes., Conclusions: We found that lower SES and peripheral residence were associated with deleterious outcomes in IBD. This should be considered by policymakers and should encourage strategies for improving outcomes in populations at risk., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The Lymphocyte-Activation Protein 3 (LAG-3) inhibitory receptor is expressed on regulatory plasma cells (PCs). Micro-environmental cells that express LAG-3 were found to be increased during the progression of smoldering multiple myeloma (SMM). To assess the possible role of LAG-3 expression on regulatory PCs in patients with plasma cell dyscrasia. Purified Cluster of Differentiation 138 (CD138 +) PCs from patients with premalignant conditions, active multiple myeloma (MM), and controls were analyzed for the expression of LAG-3 by flow cytometry. Autologous CD8 + T cells were incubated with sorted LAG-3 pos or LAG-3 neg PCs for 24 h. The expression of granzyme (Grz) in CD8 + T cells was assessed by flow cytometry. LAG-3 expression on PCs in active MM (newly diagnosed and relapse refractory MM) was significantly increased compared to monoclonal gammopathy of undetermined significance (MGUS)/ SMM. Grz expression was significantly decreased in CD8 + T cells incubated with CD138 + LAG-3 pos PCs, compared to CD138 + LAG-3 neg PCs in patients with plasma cell dyscrasia, n = 31, p = 0.0041. LAG-3 expression on malignant PCs can be involved in the development of MM from MGUS by decreasing the expression of Grz in CD8 + T cells.

Background: Israel has a high rate of Jewish immigration and a high prevalence of inflammatory bowel disease (IBD)., Aim: To compare IBD prevalence in first-generation immigrants vs Israel-born Jews., Methods: Patients with a diagnosis of IBD as of June 2020 were included from the validated epi-IIRN (Israeli IBD Research Nucleus) cohort that includes 98% of the Israeli population. We stratified the immigration cohort by IBD risk according to country of origin, time period of immigration, and age group as of June 2020., Results: A total of 33544 patients were ascertained, of whom 18524 (55%) had Crohn's disease (CD) and 15020 (45%) had ulcerative colitis (UC); 28394 (85%) were Israel-born and 5150 (15%) were immigrants. UC was more prevalent in immigrants (2717; 53%) than in non-immigrants (12303, 43%, P < 0.001), especially in the < 1990 immigration period. After adjusting for age, longer duration in Israel was associated with a higher point prevalence rate in June 2020 (high-risk origin: Immigration < 1990: 645.9/100000, ≥ 1990: 613.2/100000, P = 0.043; intermediate/low-risk origin: < 1990: 540.5/100000, ≥ 1990: 192.0/100000, P < 0.001). The prevalence was higher in patients immigrating from countries with high risk for IBD (561.4/100000) than those originating from intermediate-/low-risk countries (514.3/100000; P < 0.001); non-immigrant prevalence was 528.9/100000., Conclusion: Lending support to the environmental effect on IBD etiology, we found that among immigrants to Israel, the prevalence of IBD increased with longer time since immigration, and was related to the risk of IBD in the country of origin. The UC rate was higher than that of CD only in those immigrating in earlier time periods., Competing Interests: Conflict-of-interest statement: All the authors declare that they have no conflicts of interest to disclose., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Thiopurines and methotrexate have long been used to maintain remission in Crohn's disease [CD]. In this nationwide study, we aimed to compare the effectiveness and safety of these drugs in CD., Methods: We used data from the epi-IIRN cohort, including all patients with CD diagnosed in Israel. Outcomes were compared by propensity-score matching and included therapeutic failure, hospitalisations, surgeries, steroid dependency, and adverse events., Results: Of the 19264 patients diagnosed with CD since 2005, 3885 [20%] ever received thiopurines as monotherapy and 553 [2.9%] received methotrexate. Whereas the use of thiopurines declined from 22% in 2012-2015 to 12% in 2017-2020, the use of methotrexate remained stable. The probability of sustaining therapy at 1, 3, and 5 years was 64%, 51%, and 44% for thiopurines and 56%, 30%, and 23% for methotrexate, respectively [p <0.001]. Propensity-score matching, including 303 patients [202 with thiopurines, 101 with methotrexate], demonstrated a higher rate of 5-year durability for thiopurines [40%] than methotrexate [18%; p <0.001]. Time to steroid dependency [p = 0.9], hospitalisation [p = 0.8], and surgery [p = 0.1] were comparable between groups. These outcomes reflect also shorter median time to biologics with methotrexate (2.2 [IQR 1.6-3.1 years) versus thiopurines (6.6 [2.4-8.5]; p = 0.02). The overall adverse events rate was higher with thiopurines [20%] than methotrexate [12%; p <0.001], including three lymphoma cases in males, although the difference was not significant [4.8 vs 0 cases/10 000 treatment-years, respectively; p = 0.6]., Conclusion: Thiopurines demonstrated higher treatment durability than methotrexate but more frequent adverse events. However, disease outcomes were similar, partly due to more frequent escalation to biologics with methotrexate., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Deep learning approaches are gradually being applied to electronic health record (EHR) data, but they fail to incorporate medical diagnosis codes and real-valued laboratory tests into a single input sequence for temporal modeling. Therefore, the modeling misses the existing medical interrelations among codes and lab test results that should be exploited to promote early disease detection. To find connections between past diagnoses, represented by medical codes, and real-valued laboratory tests, in order to exploit the full potential of the EHR in medical diagnosis, we present a novel method to embed the two sources of data into a recurrent neural network. Experimenting with a database of Crohn's disease (CD), a type of inflammatory bowel disease, patients and their controls (~1:2.2), we show that the introduction of lab test results improves the network's predictive performance more than the introduction of past diagnoses but also, surprisingly, more than when both are combined. In addition, using bootstrapping, we generalize the analysis of the imbalanced database to a medical condition that simulates real-life prevalence of a high-risk CD group of first-degree relatives with results that make our embedding method ready to screen this group in the population., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Different antibiotic classes were reported to have variable effects on immunogenicity towards anti-tumour necrosis factor [TNF] agents. However, the impact of antibiotic administration on biologic treatment durability was not investigated. We aimed to assess the association between antibiotic treatment and persistence of different classes of biologic therapy in inflammatory bowel disease [IBD] patients., Methods: Data from the epi-IIRN, a nationwide registry of all Israeli IBD patients were analysed. All patients who filled a prescription of either infliximab, adalimumab, vedolizumab, or ustekinumab, were included. Treatment cessation was defined as drug discontinuation of at least 6 months. Macrolides, cephalosporins, fluoroquinolones, and penicillins with beta-lactamase inhibitors were selected as primary exposure variables. Survival analysis was performed using marginal structural models for each drug separately., Results: In all 13 513 IBD patients, with a total of 39 600 patient-years, were included. Significant differences of overall treatment persistence were demonstrated, with highest persistence rates for ustekinumab and the lowest for infliximab treatment. Macrolides were found to be significantly associated with reduced risk of infliximab cessation (adjusted hazard ratio [aHR] 0.72, 95% CI 0.62-0.89]. Fluoroquinolones and cephalosporins were associated with an elevated risk of adalimumab treatment cessation [aHR 1.33, 95% CI 1.22-1.46; and aHR 1.20, 95% CI 1.08-1.34, respectively]. No significant effects of the studied antibiotics were observed in ustekinumab and vedolizumab users., Conclusions: Specific antibiotic classes are associated with duration of anti-TNF treatment, but not with durability of vedolizumab or ustekinumab treatments. Further research is required to study the effect of specific antibiotics on response to biologics., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)