Predictors of Complicated Disease Course in Adults and Children With Crohn's Disease: A Nationwide Study from the epi-IIRN.

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.

Prognostic factors of complicated disease course are vital for considering early escalation to biologics. In this nationwide cohort, complicated disease course was apparent in approximately one-fourth of patients and was predicted particularly by routinely collected laboratory tests, age, and type of induction therapy at diagnosis.

Factors associated with corticosteroid use in Crohn's disease and ulcerative colitis patients in Israel: A multicenter cross-sectional study.

BACKGROUND: We examined corticosteroid use among Israeli patients with Inflammatory Bowel Disease (IBD), focusing on demographic, disease-related, and psychosocial factors. The objective was to contribute to the development of strategies minimizing corticosteroid dependence and improving patient outcomes, given the adverse effects associated with prolonged corticosteroid use. METHODS: A comprehensive analysis was conducted on data collected from adult IBD patients attending six gastroenterological outpatient clinics in Israel. The data collected encompassed disease characteristics, demographic information, service level characteristics, social data, and steroid use. Statistical analyses were performed to associate these variables with steroid use. RESULTS: Out of 402 patients, 26 % had been treated with corticosteroids in the previous year, with a majority of these having only one treatment course. Of patients treated with steroids, 57% (n-44) met steroid dependent/excess criteria. Steroid use was more common in patients diagnosed with ulcerative colitis (UC) compared to those with Crohn's disease. Factors such as a diagnosis of UC, male gender, elevated C-reactive protein and fecal calprotectin, and decreased albumin and hemoglobin were associated with steroid use. CONCLUSION: Corticosteroid use among Israeli IBD patients was associated with disease-related factors and some demographic characteristics. The results highlight the need for continued research to inform strategies aimed at reducing corticosteroid dependence in managing IBD, thereby improving patient outcomes.

Prevalence and Outcomes of No Treatment Versus 5-ASA in Ulcerative Colitis: A Nationwide Analysis From the epi-IIRN.

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 rate of no maintenance treatment (NMT) decreased in the last years, but in a propensity score­matched analysis, 5-aminosalicylic acid monotherapy did not demonstrate any therapeutic advantage over NMT. NMT seems to be a viable option in a subset of patients with mild ulcerative colitis.

Dysplasia detection rates under a surveillance program in a tertiary referral center for inflammatory bowel diseases: Real-world data.

BACKGROUND AND AIMS: Surveillance colonoscopies are crucial for high-risk patients with inflammatory bowel diseases (IBD) to detect colorectal carcinoma (CRC). However, there is no established quality metric for dysplasia detection rate (DDR) in IBD surveillance. This study assessed the DDR in a dedicated surveillance program at a tertiary referral center for IBD. METHODS: Consecutive patients with quiescent colitis were enrolled in a cross-sectional study evaluating DDR. High-definition colonoscopy with dye chromoendoscopy (DCE) was performed by a specialized operator. Advanced dysplasia (AD) was defined as low-grade dysplasia ≥ 10 mm, high-grade dysplasia, or colorectal cancer. Risk factors for dysplasia detection were analyzed. RESULTS: In total, 119 patients underwent 151 procedures, identifying 206 lesions, of which 40 dysplastic with seven AD . Per-lesion and per-procedure DDR were 19.4 % and 20.5 %, respectively. The per-procedure AD detection rate (ADDR) was 4.6 %. A Kudo pit pattern of II-V had a sensitivity of 92.5 % for dysplasia detection but a false positive rate of 64.8 % (p < 0.001). Age at diagnosis and at index colonoscopy and past or indefinite dysplasia were associated with per-procedure dysplasia detection. CONCLUSIONS: In a real-world setting, a dedicated surveillance program achieved a high DDR. We suggest that optimal DDR in high-risk IBD patients be defined and implemented as a standardized quality measure for surveillance programs.

Curcumin-QingDai Combination for Patients With Active Ulcerative Colitis: A Randomized, Double-Blinded, Placebo-Controlled Trial.

BACKGROUND & AIMS: We evaluated the efficacy of herbal combination of curcumin-QingDai (CurQD) in active ulcerative colitis (UC). METHODS: Part I was an open-label trial of CurQD in patients with active UC, defined by a Simple Clinical Colitis Activity Index score of 5 or higher and a Mayo endoscopic subscore of 2 or higher. Part II was a placebo-controlled trial conducted in Israel and Greece, randomizing active UC patients at a 2:1 ratio to enteric-coated CurQD 3 g/d or placebo for 8 weeks. The co-primary outcome was clinical response (reduction in the Simple Clinical Colitis Activity Index of ≥3 points) and an objective response (Mayo endoscopic subscore improvement of ≥1 or a 50% fecal calprotectin reduction). Responding patients continued either maintenance curcumin or placebo alone for an additional 8 weeks. Aryl-hydrocarbon receptor activation was assessed by cytochrome P450 1A1 (CYP1A1) mucosal expression. RESULTS: In part I, 7 of 10 patients responded and 3 of 10 achieved clinical remission. Of 42 patients in part II, the week 8 co-primary outcome was achieved in 43% and 8% of CurQD and placebo patients, respectively (P = .033). Clinical response was observed in 85.7% vs 30.7% (P < .001), clinical remission in 14 of 28 (50%) vs 1 of 13 (8%; P = .01), a 50% calprotectin reduction in 46.4% vs 15.4% (P = .08), and endoscopic improvement in 75% vs 20% (P = .036) in the CurQD and placebo groups, respectively. Adverse events were comparable between groups. By week 16, curcumin-maintained clinical response, clinical remission, and clinical biomarker response rates were 93%, 80%, and 40%, respectively. CurQD uniquely up-regulated mucosal CYP1A1 expression, which was not observed among patients receiving placebo, mesalamine, or biologics. CONCLUSIONS: In this placebo-controlled trial, CurQD was effective for inducing response and remission in active UC patients. The aryl-hydrocarbon receptor pathway may merit further study as a potential UC treatment target. CLINICALTRIALS: gov ID: NCT03720002.

Mesenchymal stem cell therapy for Crohn's perianal fistula-a real-world experience.

AIM: Remission rates of medically and surgically treated complex perianal fistulas in Crohn's disease are low. Recently, trials have demonstrated the potential for long-term remission with local injection of allogeneic adipose-derived mesenchymal stem cells (darvadstrocel). Our aim was to analyse outcomes from our real-world experience with this new treatment. METHODS: All patients with Crohn's disease suffering complex perianal fistulas who consecutively underwent administration of darvadstrocel at two centres were followed up and evaluated. Patients were assessed for clinical remission, response, failure, and any complications during follow-up. The results of all patients with a minimum of 3 months' follow-up are presented. RESULTS: Thirty-three patients with Crohn's disease and complex perianal fistulas were included. Of these, 20 (61%) experienced clinical remission that was maintained for a mean follow-up of 14 (3-32) months. A total of 24 of 33 (73%) experienced at least 3 months of clinical remission, with four later having recurrence (3-12 months). Among the remaining nine patients who did not experience clinical remission, two (6%) had partial remission (such as one of two fistulas closing), two (6%) showed signs of response but not remission, and five (15%) showed no signs of healing. The mean time to maintained clinical remission was 6 weeks (range 2 weeks to 6 months), and there were no severe adverse events. CONCLUSION: In this real-world experience, treatment of Crohn's disease complex perianal fistulas with darvadstrocel had a 61% success rate for maintained clinical remission.

Early Initiation of Adalimumab Significantly Diminishes Postoperative Crohn's Disease Endoscopic Recurrence and Is Superior to 6-Mercaptopurine Therapy: An Open-Label, Randomized Controlled Study.

Postoperative recurrence (POR) is the rule in patients with Crohn's disease (CD), mitigated with prophylactic therapy. The evidence for therapeutic choice and timing of intervention is lacking. We aimed to compare the rates of POR in patients treated early with prophylactic 6-mercaptopurine (6-MP) or adalimumab. We conducted a prospective single-center randomized open-label clinical study in which patients in surgical remission following their first ileocecectomy were randomized to receive early treatment with 6-MP or adalimumab. Patients were followed up clinically every 3 months and underwent endoscopy at weeks 32 and 58 postoperatively. The primary endpoint was endoscopic recurrence (ePOR) at 1 year (week 58), defined as a Rutgeerts score ≥ i2. We enrolled 35 patients (25 males, mean age 35 ± 1.4 years, median disease duration 5 ± 6.1 years) following ileocecectomy. Of these, seven (20%) were current smokers and nine (26%) biologics-experienced. Patients allocated to adalimumab had significantly less ePOR than patients treated with 6MP at week 32 (21% vs. 69%, p = 0.004) and 58 (47% vs. 75%), (p = 0.03, HR = 0.39, 95% CI = 0.16-0.93). POR was associated with an increased diameter of the resected small bowel surgical specimen, lower baseline body mass index (BMI), increased week 18 fecal calprotectin, increased week 18 serum alanine aminotransferase and decreased week 18 hemoglobin level. Adalimumab was more effective than 6-MP in preventing ePOR. Increased operative small bowel diameter and lower postoperative BMI were associated with ePOR. At eighteen weeks, serum hemoglobin, ALT and fecal calprotectin levels were predictive of endoscopic disease recurrence. (ClinicalTrials.gov ID NCT01629628).

A Real-World Prospective Cohort Study of Patients With Newly Diagnosed Crohn's Disease Treated by a Multidisciplinary Team: 1-Year Outcomes.

Background: Real-world data on outcomes of patients with newly diagnosed Crohn's disease (ndCD) is limited. We aimed to assess the achievement of corticosteroid-free clinical remission (CS-free CR) and other therapeutic targets 1 year after diagnosis in a cohort of patients with ndCD treated by a multidisciplinary team (MDT). Methods: A prospective observational cohort study was conducted on consecutive treatment-naïve adults with ndCD. Patients received management at the treating physician's discretion, along with a tailored nutritional plan provided by an inflammatory bowel disease (IBD)-oriented dietitian. Patients were guided and educated by an IBD nurse, with flexible communication access to the IBD team. Therapeutic targets were assessed at 1 year. Multivariable logistic regression was used to evaluate predictors of CS-free CR. Results: Seventy-six patients (50% female) with a median age of 27 (22-39) years were eligible. Over 75% of patients were assessed by IBD-oriented dietitians and the IBD nurse. Within a median of 4.3 (2.5-6.7) months from diagnosis 60.5% initiated biologics (96% anti- tumor necrosis factor). Dietary intervention was applied to 77.6% of the cohort, either monotherapy (33.9%) or add-on (66.1%). At 1 year, 64.5% of patients achieved sustained CS-free CR, 56.6% biochemical remission, 55.8% endoscopic response, 44.2% endoscopic remission, 30.8% deep remission, and in 39.5% there was an improvement in health-related quality of life (HRQoL). Predictors for CS-free CR were uncomplicated phenotype (B1/P0), lower body mass index, and lower patient-reported outcome 2 scores at diagnosis. Conclusions: In a real-world setting at a tertiary medical center, a cohort of ndCD patients treated by an MDT resulted in favorable 1-year outcomes. Over 60% achieved CS-free CR, along with significant improvements in biomarkers and HRQoL.

The Crohn's Disease Exclusion Diet: A Comprehensive Review of Evidence, Implementation Strategies, Practical Guidance, and Future Directions.

Dietary therapy is increasingly recognized for the management of Crohn's disease (CD) over recent years, including the use of exclusive enteral nutrition (EEN) as first-line therapy for pediatric CD according to current guidelines. The Crohn's disease exclusion diet (CDED) is a whole-food diet designed to reduce exposure to dietary components that are potentially pro-inflammatory, mediated by negative effects on the gut microbiota, immune response, and the intestinal barrier. The CDED has emerged as a valid alternative to EEN with cumulative evidence, including randomized controlled trials, supporting use for induction of remission and possibly maintenance in children and adults. We gathered a group of multidisciplinary experts, including pediatric and adult gastroenterologists, inflammatory bowel diseases (IBD) expert dietitians, and a psychologist to discuss the evidence, identify gaps, and provide insights into improving the use of CDED based on a comprehensive review of CDED literature and professional experience. This article reviews the management of CDED in both children and adults, long-term aspects of CDED, indications and contraindications, selecting the best candidates, identifying challenges with CDED, globalization, the role of the multidisciplinary team, especially of dietitian, and future directions. We concluded that CDED is an established dietary therapy that could serve as an alternative to EEN in many pediatric and adult cases, especially with mild to moderate disease. In severe disease, complicated phenotypes, or with extraintestinal involvement, CDED should be considered on a case-by-case basis, according to physician and dietitians' discretion. More studies are warranted to assess the efficacy of CDED in different scenarios.

The Crohn's disease exclusion diet (CDED) has emerged as an alternative to exclusive enteral nutrition for the treatment of pediatric Crohn's disease. In this review, we summarize data on efficacy and challenges and identify research priorities, clinical gaps, and opportunities.

The Impact of Crohn's Perianal Fistula on Quality of Life: Results of an International Patient Survey.

Background: Crohn's perianal fistula is a disabling manifestation of Crohn's disease. However, the additional burden of perianal fistula on patients with only Crohn's disease remains to be addressed. This patient-reported survey considered outcomes of two domains: "diagnosis" (eg, symptoms) and "living with the disease" (eg, quality of life, well-being, and relationships). Methods: Patients with perianal fistula and Crohn's disease completed an online, self-selective, anonymous, 46-item survey available in 11 languages hosted on the European Federation of Crohn's & Ulcerative Colitis Associations and national patient association websites. The survey was conducted between July and December 2019 in Europe and other regions. Likert scales and closed questions were used to assess outcomes. Results: Of the 820 respondents with Crohn's disease (67.2% women; median age, 40.0 years), 532 (64.9%) reported the presence of perianal fistula. Patients with perianal fistula reported a greater impact on overall quality of life (P < .001), well-being (P < .001), relationships (P < .001), social life (P = .001), and work life (P = .012) than patients with only Crohn's disease. Conclusions: Perianal fistulas impact several domains of the life of patients with Crohn's disease. These results may help healthcare practitioners plan therapeutic strategies that address the symptomatic and psychological burden experienced by patients with perianal fistulizing Crohn's disease.

Real-Life Efficacy of Tofacitinib in Various Situations in Ulcerative Colitis: A Retrospective Worldwide Multicenter Collaborative Study.

BACKGROUND AND AIMS: Tofacitinib (TFB) appears to be effective in the treatment of ulcerative colitis (UC); however, available real-world studies are limited by cohort size. TFB could be an option in the treatment of acute severe ulcerative colitis (ASUC). We aimed to investigate efficacy and safety of TFB in moderate-to-severe colitis and ASUC. METHODS: This retrospective, international cohort study enrolling UC patients with ≥6-week follow-up period was conducted from February 1 to July 31, 2022. Indications were categorized as ASUC and chronic activity (CA). Baseline demographic and clinical data were obtained. Steroid-free remission (SFR), colectomy, and safety data were analyzed. RESULTS: A total of 391 UC patients (median age 38 [interquartile range, 28-47] years; follow-up period 26 [interquartile range, 14-52] weeks) were included. A total of 27.1% received TFB in ASUC. SFR rates were 23.7% (ASUC: 26.0%, CA: 22.8%) at week 12 and 41.1% (ASUC: 34.2%, CA: 43.5%) at week 52. The baseline partial Mayo score (odds ratio [OR], 0.850; P = .006) was negatively associated with week 12 SFR, while biologic-naïve patients (OR, 2.078; P = .04) more likely achieved week 52 SFR. The colectomy rate at week 52 was higher in ASUC group (17.6% vs 5.7%; P < .001) and decreased with age (OR, 0.94; P = .013). A total of 67 adverse events were reported, and 17.9% resulted in cessation of TFB. One case of thromboembolic event was reported. CONCLUSIONS: TFB is effective in both studied indications. TFB treatment resulted in high rates of SFR in the short and long terms. Higher baseline disease activity and previous biological therapies decreased efficacy. No new adverse event signals were found.

Vedolizumab Is Associated with Longer Drug Sustainability Compared to Infliximab in Moderate-to-Severe Ulcerative Colitis: Long-Term Real-World Cohort Data.

BACKGROUND AND AIM: Drug sustainability (DS) is a surrogate marker for treatment efficacy. We aimed to compare the DS of two main biologics used to treat moderate-to-severe ulcerative colitis (UC), infliximab (IFX) and vedolizumab (VDZ), in a real-world setting. METHODS: We conducted a retrospective cohort study at a tertiary medical center in Israel. We included patients treated between 1 December 2017 and 1 May 2021, who were followed for up to 300 weeks. DS was defined as corticosteroid-, surgical-, and hospitalization-free treatment. RESULTS: 217 patients with UC were included. VDZ had a significantly longer median DS of 265.6 weeks compared to IFX's 106.5 weeks (p = 0.001) in treatment-naïve patients, even when adjusting for disease severity (HR 0.55 95 CI 0.3-0.98, p = 0.042). In treatment-experienced patients, DS was comparable between IFX and VDZ (p = 0.593). CONCLUSIONS: VDZ showed significantly longer DS in treatment-naïve patients with UC compared to IFX, also when adjusted for disease severity. There was no difference in DS between VDZ and IFX in treatment-experienced patients and patients switching from one drug to another. VDZ may be a suitable first-line treatment for biologic-naïve patients with moderate-to-severe UC.

Serologic Response and Safety after a Third Dose of the COVID-19 BNT162b2 Vaccine in Patients with Inflammatory Bowel Diseases.

Vaccines are pivotal for control of the coronavirus disease (COVID-19) pandemic. Patients with inflammatory bowel diseases (IBDs) treated with antitumor necrosis factor (TNF)-α have lower serologic response after two COVID-19 vaccine doses. Data regarding a third vaccine dose are scarce. An Israeli multicenter prospective observational study recruited 319 subjects: 220 with IBD (79 treated with anti-TNFα) and 99 healthy control (HC) participants. All patients received two mRNA-BNT162b2 vaccines (Pfizer/BioNTech), 80% of whom received a third vaccine dose. Evaluation included disease activity, anti-spike (S) and nucleocapsid (N) antibody levels, anti-TNFα drug levels, and adverse events (AEs). All participants showed significant serologic response one month after receiving a third dose. However, three months later, the anti-S levels decreased significantly in patients treated with anti-TNFα compared with the non-anti-TNFα and HC groups. A correlation between serologic response to the third vaccine dose and anti-TNF drug levels was not found. No significant AE or IBD exacerbation was observed. Importantly, lower serologic response after the third vaccine dose predicted infection. A third dose of BNT162b2 is effective and safe in patients with IBD. Lower serologic response predicted infection, even in seropositive subjects. Lower serologic responses and their rapid decline suggest a fourth vaccine dose in this patient population.

Pregnancy Outcomes in a Cohort of Patients with Inflammatory Bowel Disease: Data from a Multidisciplinary Clinic in a Tertiary Center.

BACKGROUND: Inflammatory bowel disease (IBD) can have an impact on pregnancy outcomes due to the effect of the disease activity and medication use. This study aimed to evaluate the pregnancy outcomes in IBD patients treated at a multidisciplinary clinic. METHODS: This study was a retrospective cohort study including consecutive pregnant patients with IBD having a singleton gestation attending a multidisciplinary clinic between 2012 and 2019. The IBD activity and management throughout gestation were assessed. The pregnancy outcomes included: adverse neonatal and maternal outcomes, mode of delivery, and three integrative outcomes: (1) a favorable pregnancy outcome, (2) a poor pregnancy outcome, and (3) an unfavorable maternal outcome. The IBD pregnant cohort was compared with a cohort of non-IBD pregnant women delivering at the same shift. Multivariable logistic regression was used for risk assessment. RESULTS: Pregnant women with IBD (141) and without (1119) were included. Mean maternal age was 32 [±4] years. Patients with IBD had a higher rate of nulliparity (70/141 (50%) vs. 340/1119 (30%), p < 0.001) and lower BMI (21.42 kg/m2 (19.18-23.44) vs. 22.48 (20.31-25.59), p = 0.002). All the other characteristics were comparable. Most patients with IBD 124/141 (88%) were in clinical remission at conception; with maintenance therapy in 117/141 patients (83%). A third of the patients, 43/141 (30.5%), were treated with biologics. Exacerbation occurred during pregnancy in 51/141 (36%). The majority of the maternal and neonatal outcomes and all the composite outcomes were comparable between the patients with IBD and the women without IBD. Cesarean delivery was more frequent in patients with IBD (49/141 (34.8%) vs. 270/1119 (24.1%), p = 0.021). IBD was not associated with composite outcomes. CONCLUSIONS: In pregnant patients with IBD followed at a multidisciplinary clinic, the pregnancy outcomes were encouraging and comparable to those of the women without IBD.

Real-world experience with Curcumin-QingDai combination for patients with active ulcerative colitis: A retrospective multicentre cohort study.

BACKGROUND: Curcumin and QingDai (QD, Indigo) have been shown to be effective for treating active ulcerative colitis (UC). AIM: To evaluate the real-world experience with the Curcumin-QingDai (CurQD) herbal combination to induce remission in active UC. METHODS: A retrospec-tive multicentre adult cohort study from five tertiary academic centres (2018-2022). Active UC was defined as a Simple Clinical Colitis Activity Index (SCCAI) ≥ 3. Patients were induced by CurQD. The primary outcome was clinical remission at weeks 8-12, defined as SCCAI ≤2 and a decrease ≥3 points from baseline. Secondary outcomes were clinical response (SCCAI decrease ≥3 points), corticosteroid-free remission, faecal calprotectin (FC) response (reduction ≥50%), FC normalisation (FC ≤100 µg/g for patients with FC ≥300 µg/g at baseline), and safety. All outcomes were analysed for patients who were maintaining stable treatment. RESULTS: Eighty-eight patients were included; 50% were biologics/small molecules experienced, and 36.5% received ≥2 biologics/small molecules. Clinical remission was achieved in 41 (46.5%), and clinical response in 53 (60.2%). Median SCCAI decreased from 7 (IQR:5-9) to 2 (IQR:1-3); p < 0.0001. Of the 26 patients on corticosteroids at baseline, seven achieved corticosteroid-free remission. Among 43 biologics/small molecules experienced patients, clinical remission was achieved in 39.5% and clinical response in 58.1%. FC normalisation and response were achieved in 17/29 and 27/33, respectively. Median FC decreased from 1000 µg/g (IQR:392-2772) at baseline to 75 µg/g (IQR:12-136) at the end of inductions (n = 30 patients with paired samples); p < 0.0001. No overt safety signals emerged. CONCLUSION: In this real-world cohort, CurQD effectively induced clinical and biomarker remission in patients with active UC, including patients who were biologics/small molecules experienced.

Thiopurines Have Longer Treatment Durability than Methotrexate in Adults and Children with Crohn's Disease: A Nationwide Analysis from the epi-IIRN Cohort.

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.