5-ASA Use Research Articles

Banxia Xiexin decoction combined with 5-ASA protects against CPT-11-induced intestinal dysfunction in rats via inhibiting TLR4/NF-κB signaling pathway.

Banxia Xiexin decoction (BXD) can control irinotecan (CPT-11)-caused delayed diarrhea, but the corresponding mechanism remains undefined. This paper aimed to uncover the mechanism of BXD in regulating CPT-11-caused delayed diarrhea. Sprague-Dawley (SD) rats were assigned into the control, model, BXD low-dose (BXD-L, 5 g/kg), BXD medium-dose (BXD-M, 10 g/kg), BXD high-dose (BXD-H, 15 g/kg), 5-aminosalicylic acid (5-ASA, 10 mL/kg), and BXD-M + 5-ASA groups. Rats were injected intraperitoneally with 150 mg/kg CPT-11 at Day 4 and Day 5 to induce delayed diarrhea, and later treated with various doses (low, medium, and high) of BXD and 5-ASA for 9 days, except for rats in control group. The body weight of rats was measured. The rat colon tissue injury, inflammatory cytokine levels, and the activation of toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) signaling pathway were detected. BXD (5, 10, or 15 g/kg) or 5-ASA (10 mL/kg) alleviated body weight loss and colon tissue injury, decreased levels of inflammatory cytokines, and inactivated TLR4/NF-κB signaling pathway in CPT-11-induced model rats. BXD at 10 g/kg (the optimal concentration) could better treat CPT-11-induced intestinal dysfunction, as evidenced by the resulting approximately 50% reduction on injury score of model rats. Moreover, BXD-M (10 g/kg) synergistic with 5-ASA (10 mL/kg) further strengthened the inhibition on rat body weight loss, colon tissue injury, inflammatory cytokine levels, and TLR4/NF-κB signaling pathway. To sum up, BXD has a protective effect against CPT-11-induced intestinal dysfunction by inhibiting inflammation through inactivation TLR4/NF-κB signaling pathway. In particular, the combined use of BXD and 5-ASA holds great promise for treating CPT-11-induced delayed diarrhea.

Prescribing in pregnant women with inflammatory bowel disease and its relationship to congenital malformations in Japan.

Inflammatory bowel disease (IBD) frequently affects younger patients and poses various challenges concerning pregnancy and childbirth. Maintaining good disease control throughout pregnancy is crucial, but expectant and pregnant patients may worry about the fetal impact of medications, leading to treatment discontinuation due to uncertainty about this issue. This study investigated the real-world drug-prescribing practices for pregnant patients with IBD in Japan and their potential connection to major congenital malformations (MCMs). Overall, 277 female IBD patients who gave birth between 2010 and 2019 were selected from the JMDC claims database. The prescribing patterns of IBD medications and MCMs in the patients' offspring were analyzed. Among pregnant IBD patients, 74.4% received at least one medication from 90days before pregnancy to 90days after delivery. Trends in medication prescriptions during pregnancy in 2010-2019 revealed consistent use of oral 5-ASA, variable use of topical medications, a decrease in systemic steroids, and an increase in biologics. The prevalence of MCMs in children born to IBD-affected mothers did not differ significantly between those who did and did not receive IBD medications (8.6% vs 6.8%). Although circulatory system MCMs were slightly more common in the IBD medication group (4.9% vs 1.4%), this difference was not significant. Logistic regression analysis did not reveal an association between MCM risk and first-trimester use of IBD medications, including corticosteroids and biologics. This study provides insights into medication patterns in pregnant IBD patients and suggests no increased risk of MCMs associated with first-trimester IBD medication use.

P561 Reasons for low use of topical 5-ASA formulations in patients treated for ulcerative colitis: comparison of doctors and patients perspectives

Abstract Background Ulcerative colitis (UC) is a chronic relapsing inflammatory disorder of the colon. In patients with proctitis or left sided colitis, topical application of 5-ASA as suppository, enema or foam preparation has been shown more effective as compared to systemic treatment. In a study conducted 10 years ago, we observed an underuse of topical therapy in patients with UC. Objectives to assess the current use of topical 5-ASA for UC and compare it with previous findings. To evaluate perspectives on use of topical therapies, among physician and patients. Methods The study had two parts. We first conducted a retrospective cohort data analysis, among adult UC patients included in the SIBDCS. We included patients enrolled since 2012 (not included in our previous study), and to compare the results of the use of 5-ASA therapies from 2021-2021. We then conducted two parallel surveys: with patient and with gastroenterologists. The survey was independent from the cohort data analysis. We assessed potential reasons for low use of topical therapies. Results 721 patients were included in the retrospective study (329 (45.6%) females, age at diagnostic (median, IQR): 31 (23-42), disease duration: 6 (2-15)). Disease extension at last FU was 18.0% proctitis, 26.3% proctosigmoiditis; clinical activity was low to moderate in 18.6%, and high in 1.8% of patients. 16.4% of patients with proctitis received topical 5-ASA only (5-ASA top+oral (5ASA): 42.2%), 5.9% with proctosigmoiditis (16.6% 5ASA), 0% in left-sided colitis (9.3% 5ASA) (figure 1). Exclusive 5-ASA topical use was lower than observed 10 years ago (23.3%) in proctitis. The survey was completed by 142 patients: 89 females (63%), mean (SD) age 46 (13) and disease duration 15 (10), 15% had proctitis/proctosigmoiditis and 29% left-sided colitis. 63 gastroenterologists participated in the survey; 25% were females, 36.5% had a professional experience up to 10 years, 55% were in single/group practice. 76% of patients reported having ever been prescribed suppositories (S), 74% foam (F), 61% enema (E). Patients-reported top reasons for stopping topical therapy prematurely (1/3 of cases) were unpleasantness (51.3% F/E, 13.9% S), ineffectiveness (41.1% F/E, 60.5% S), and preference for tablets (51.3% F/E, 37.8% S). Physicians’ perspectives on compliance difficulties were unpleasantness (83.7% F/E, 56.3% S), and preference for tablets (76.4% F/E, 63.7% S). 85% of patients were well informed on rectal therapies, 76% of doctors would be open for training/update on rectal therapies. Conclusion The use of rectal therapies in UC patients that should benefit from is still low. Reasons for non-compliance were discordant between doctors and patients.

P667 Benefit of 5-ASA continuation on UC disease outcomes following initiation of a biologic

Abstract Background In the era of advanced therapeutics for treatment of ulcerative colitis (UC) the benefit of routinely prescribed concomitant 5-aminosalicylate (5-ASA) compounds is still unclear. Methods A single centre, noninterventional retrospective cohort review study was performed on real-life data of adult patients with moderate-to-severe UC who were treated with biologics (infliximab, vedolizumab, ustekinumab) for a minimum of 6 months with or without concomitant use of 5-ASA. The difference in further treatment failure defined as a clinical negative composite outcome (need for steroid rescue therapy, biologic switch, IBD-related hospitalization and/or surgery) in two groups (5-ASA + biologic combination therapy vs biologic monotherapy) was assessed. Participants’ characteristics were assessed using descriptive statistics. Normal distribution was assessed using Kolmogorov-Smirnov and Shapiro-Wilk tests. Categorical variables were analysed using Chi-square test and continuous variables with Mann-Whitney test. Kaplan-Meier analysis and log-rank test were used in order to assess difference in therapy duration between two groups. Results Total of 104 patients (47.1% females; smokers 17.6%; concomitant stable dose oral 5-ASA 33%) were included. There were no differences in key baseline characteristics such as age, sex, smoking status, extraintestinal manifestations, serum albumin and CRP as well as fecal calprotectin levels between groups of patients receiving 5-ASA co-treatment and patients without 5-ASA. Median duration of therapy was 21 months (IQR 9-40). Concomitant use of 5-ASA was not associated with improved clinical outcomes; there was no statistically significant difference in the occurrence (χ2(1, N =102)=2.2, p=0.14) or time to develop (χ2(1, N =102)=1.12, p=0.29; Figure 1.) negative composite outcomes. Conclusion In our cohort we have failed to detect any benefit of 5-ASA continuation on significant clinical adverse events or hospitalisations in UC following initiation of a biologic.

P1000 A meta-analysis and systematic review of 5-aminosalicylates withdrawal in Inflammatory Bowel Disease

Abstract Background 5-aminosalicylic acids (5-ASA) are the first-line agents in mild-to-moderate ulcerative colitis (UC). They are not recommended for Crohn’s disease (CD) or moderate-to-severe UC. 5-ASAs are the most prescribed medication for all patients with inflammatory bowel diseases (IBD). Its continuous use is associated with significant cost, adverse effects, and delay in treatment escalation. Recent analyses suggest no benefit of 5-ASA use in patients escalated to more advanced therapies. Hence, 5-ASA withdrawal was suggested, but the outcomes remain unclear. We aimed to perform a meta-analysis of 5-ASA withdrawal in patients with IBD and compare the risk of disease relapse in different cohorts of patients. Methods A search for articles was conducted in five medical databases, studies were selected, and their quality was assessed. Studies were divided into six clinically relevant cohorts depending on the type of IBD and other treatments used; the relative risk of relapse for individual studies in each cohort was analysed. Results 1714 studies were identified; 27 were included in the meta-analysis. Withdrawal of oral 5-ASA monotherapy was associated with a 60% increased risk of relapse. Similarly, withdrawal of rectal 5-ASA had a relative risk of relapse of 2.03. When combined with immunomodulators and/or biologics in UC or CD, oral 5-ASA withdrawal was not associated with an increased risk of relapse. Patients on combined oral 5-ASA and immunomodulators had a higher risk of relapse in the 5-ASA continuation group across three studies; this can be attributed to the persistence of oral 5-ASA use in patients with more severe disease, delaying the appropriate escalation to advanced therapies. Two studies reported no increased risk of colorectal cancer when 5-ASA was withdrawn either as monotherapy or when combined with other treatments. Conclusion Oral or rectal 5-ASA monotherapy in UC should not be discontinued. 5-ASA withdrawal does not increase relapse in patients with UC or CD escalated to immunomodulator and/or biological treatment. Oral 5-ASA continuation combined with immunomodulators delays escalation to advanced therapy. Available data suggest that 5-ASA withdrawal does not increase the risk of colorectal cancer; however, this must be considered carefully in patients with unmodifiable risk factors.

P622 Network meta-analysis comparing efficacy between biologics and conventional therapies to prevent endoscopic postoperative recurrence in patients with Crohn's disease

Abstract Background As no direct comparison between IBD drugs to prevent endoscopic postoperative recurrence (POR) In Crohn’s disease (CD) are available, hierarchizing these therapeutic options remains challenging. The objective of this network meta-analysis was to compare the effectiveness of treatments to prevent endoscopic POR of CD. Methods We performed a systematic review and network meta-analysis of comparative studies conducted in adults, evaluating a treatment to prevent endoscopic POR after ileocecal resection. The selection of studies was made according to PRISMA guidelines. The primary endpoint was endoscopic POR at 6 months defined as Rutgeerts score ≥ i2. The network meta-analysis was carried out according to a random effects model. The results are presented as odds ratio (OR) with 95% confidence interval, adjusted for risk factors of POR. The risk of bias of the studies was assessed according to the Cochrane risk-of-bias tool for randomized trials and overall statistical heterogeneity between studies was assessed using τ². The SUCRA ranking method (surface under the cumulative ranking) was used to rank the treatments. Results Twenty studies were included in this network meta-analysis, including a total of 2414 patients. Overall heterogeneity was moderate (τ²=0.34). After adjustment for POR risk factors, ustekinumab (OR = 0.23 [0.07-0.70]), vedolizumab (OR = 0.17 [0.05 -0.59]), infliximab (OR = (0.18 [0.36-0.88]) and adalimumab (OR = 0.17 [0.07-0.42]) were superior to placebo to prevent endoscopic POR, contrary to 5-ASA (OR = 0.79 [0.42 -1.48]) and thiopurines (RR = 0.52 [0.22-1.24]) (Table 1). Ustekinumab (OR = 0.29 [0.08-0.99]), vedolizumab (OR = 0.22 [0.06-0.85]), infliximab (OR = (0.23 [0.09-0.54]) and adalimumab (OR = 0.22 [0.08-0.59]) were more effective than 5-ASA in preventing endoscopic POR. Adalimumab (OR = 0.33 [0.15-0.74]) and infliximab (OR = 0.34 [0.13-0.87]) were also more effective than thiopurines. We observed no difference in efficacy between the 4 biologics (infliximab, adalimumab, ustekinumab and vedolizumab) (Table 1). The SUCRA ranking identified adalimumab (SUCRA=0.81), infliximab (SUCRA=0.80), vedolizumab (SUCRA=0.79) and ustekinumab (SUCRA=0.72) as the most effective treatments. The likelihood that thiopurines (SUCRA=0.41), 5-ASA (SUCRA=0.24), placebo (SUCRA = 0.16) and antibiotics (SUCRA=0.08) was the best option is very low. Conclusion This network meta-analysis confirms the efficacy of anti-TNF agents, vedolizumab and ustekinumab in preventing endoscopic CD POR without any difference between them. When prophylactic therapy is necessary, biologics appear as the best therapeutic option to prevent of endoscopic POR. Due to lower efficacy, the use of 5-ASA and thiopurines should be limited in this situation.

P880 The real-world use of five-aminosalicylate (5ASA) treatment for Ulcerative Colitis in Australia and New Zealand: Crohn’s Colitis Cure (CCC) data insight’s program

Abstract Background Five-aminosalicylates (5ASAs) promote & maintain remission in people with ulcerative colitis (UC) and are administered orally or rectally, with combination therapy (oral + rectal) more effective than oral monotherapy, especially when treating flares1. 5ASAs may be perceived as out-dated and thus neglected. With increasing UC incidence & prevalence in emerging nations, understanding real-world 5ASA use and value is vital. Methods Crohn’s Colitis Care is a cloud-based electronic medical record used in Australasia. Data feed into a de-identified clinical quality registry (CQR), which was interrogated in September 2023. People with UC under active care (encounter within 14 months) were included. Results Of the 2,522 eligible people, 78.4% resided in Australia & 21.6% in New Zealand (NZ). The median age was 41 years (IQR 31-56), with an even gender distribution (50.3% female). Median disease duration was 9 years (IQR 4.4-16.7). Median duration of follow up was 25.9 months (IQR 13.0-41.4). Overall, 39.2% (n=989) had no documentation of 5ASA therapy (42.0% in Australia, 28.9% in NZ; Table 1). In those with documented 5ASA therapy (60.8%, n=1,534), the average 5ASA treatment duration was 9 years (IQR 4.4-16.7) and women were more likely to receive rectal administration than men (p<0.05). In those who ceased 5-ASA therapy, 782 (44.8%) had a reason documented, with the most common being medication rationalisation and/or deep remission (40.0%) (Figure 1), usually due to up-titration to a more advanced therapy. A total of 608 (39.6%) were recorded as already receiving additional IBD therapy at CQR entry (immunomodulators [IMs]/biologics/small molecules). Of those receiving 5ASAs alone at CQR entry (n=926), 5ASAs were subsequently judged to have failed in 37.8% (n=350). 5ASA failure was defined as the need for additional IBD therapies (99.1%, n=230 for IMs/biologics/small molecules and n=117 for steroids, total n=347); hospitalisation (n=3, 0.9%) or IBD surgery (n=0). Conclusion Despite not working for everyone, the long duration of 5ASA therapy indicates they are well tolerated & perceived as beneficial by consumers. There was greater 5ASA utilisation in NZ, possibly due to restricted advanced therapy access. Gender-specific trends in 5ASA administration were identified, raising the question as to why this should be so, given this is not obviously explained by disease phenotype. Further analysis is needed to tease out how such trends interact with other therapeutic access, choices and outcomes. 1 - Probert C et a. Combined oral and rectal mesalazine for the treatment of mild-to-moderately active ulcerative colitis: rapid symptom resolution and improvements in quality of life. J Crohns Colitis. doi:10.1016/j.crohns.2013.08.007

OP07 Consistent IBD treatment approaches across South Asian and White ethnicities despite phenotypic variations: a study of 33,157 patients using the IBD BioResource

Abstract Background The current evidence suggests ethnic distinctions in IBD phenotype, and differences in the provision of treatment have been reported. This multi-centre cohort study utilised the UK IBD BioResource dataset to evaluate phenotypic differences between South Asian (SA) and White (WH) IBD, and to explore if these were associated with differences in treatment. Methods Phenotypic and outcome data were extracted from the IBD BioResource. Chi2 (categorical data) and Mann-Whitney U (continuous data) tests were used. Propensity score matching (PSM) accounted for age at diagnosis, sex, smoking status, disease location and behaviour and perianal disease (CD). Differences in medication use (multivariable logistic regression) and surgical outcomes (Kaplan-Meier and Cox regression analysis) were assessed in propensity-matched (PM) cohorts. Results 33,157 (31,932 WH; 1225 SA) individuals were included (48.1% CD, 45.4% UC, 6.5% IBD-U). UC was the predominant disease subtype in SA (UC, SA 57.3% vs WH 44.9%, p<0.001). SA were younger at diagnosis [CD, SA 24 (IQR 17-36) vs WH 26 (IQR 19-39) years, p<0.001; UC, SA 29 (IQR 22-38) vs WH 35 (25-48) years, p<0.001]. SA CD had less ileal disease (SA 30.3% vs WH 38.4%, padj=0.008), and more perianal involvement (SA 38.5% vs WH 32.3%, p=0.009) than WH. SA CD had less stricturing disease (SA 16.9% vs WH 25.6%, padj<0.001). SA UC were more likely to have extensive disease (SA 41.7% vs WH 34.1%, padj<0.001). Initial analyses in non-PSM cohorts showed that fewer SA CD underwent surgery [SA (n=157,37.4%) vs WH (n=7532,50.4%), p<0.001], and that similar proportions of SA (n=33,5.1%) and WH (n=747,5.5%; p=0.15) UC underwent a colectomy. PSM was used to match 355 SA to 355 WH in CD, and 525 SA to 525 WH in UC. Variables were well-balanced. There were no differences in 5-ASA, corticosteroid, thiopurine, anti-TNF or Vedolizumab use (Table 1). In CD, 126 (36.5%) SA and 152 (44.7%) had surgery. Survival analysis in CD showed no difference in the time to surgery (Fig 1A, log-rank 0.28). SA ethnicity was not associated with increased risk of surgery in CD (HR 0.82, 95% CI 0.63-1.07, p=0.14). In UC, 25 (4.8%) and 37 (7.1%) WH had a colectomy. There was no significant difference in the time to colectomy (Fig 1B, log-rank 0.12) nor was SA ethnicity associated with an increased risk of having a colectomy (HR 0.65, 95% CI 0.39-1.11, p=0.12). Conclusion In the largest analysis of SA IBD to date, we have demonstrated phenotypic differences associated with ethnicity. Accounting for these variations, we have shown comparable provision of medical and surgical treatment in SA and WH. These findings indicate consistent care of IBD patients from different ethnic backgrounds in the UK.

Efficacy and safety of tacrolimus in older adults with ulcerative colitis: a retrospective study

Background/aimsThe prevalence of ulcerative colitis (UC) has been increasing, also in older adults. Here, we retrospectively compared the efficacy and safety of tacrolimus (TAC) in older and younger patients with UC.MethodsWe included younger (age < 65 years; n = 116) and older patients (age ≥ 65 years; n = 21) with UC who received TAC from April 2009 through December 2022(mean follow-up, 1230 ± 175 days) and achieved remission. Evaluations included age at onset, laboratory values, estimated glomerular filtration rate (eGFR), use of 5-aminosalicylic acid (5-ASA), biological experience, colonoscopy scores, remission at 1 month after treatment initiation, and adverse events. Treatment duration and renal function were assessed in patients with follow-up data (younger patients, n = 110; older patients, n = 19).ResultsOlder patients had a higher age at onset and treatment initiation but less 5-ASA use and biological experience. Before treatment, hemoglobin, albumin, and eGFR were significantly lower in the older group and CRP was significantly higher. The remission rate was 80.1% in the younger group and 66.6% in the older group (P = 0.1862). Adverse events were similar in both groups. The older group had a shorter treatment duration and significantly less change in renal function at all time points.DiscussionRates of TAC-induced remission and adverse events were similar in older and younger adults with UC.ConclusionTAC can be used safely in elderly patients with moderate to severe UC with careful monitoring.

Clinical and immunological analysis of the effectiveness of local application of vitamin D&lt;sub&gt;3&lt;/sub&gt; in experimental colitis

The pathogenesis of inflammatory bowel diseases has not been fully studied, and the therapies used have side effects that limit their use.The purpose of this study is to conduct a clinical and immunological analysis of the effectiveness of vitamin D3 in the original rectal suppositories in experimental colitis (EC).EC was modeled with oxazolone. Original suppositories with vitamin D3 in group 3 and 5-ASA in group 4 were used per rectum. The clinic was evaluated on the Disease activity index scale. The expression of MPO and TNFa, the content of neutrophils, lymphocytes, eosinophils, histiocytes, plasmocytes, fibroblasts, ulcerative defect, tissue damage index were determined in the focus of colon injury. The study was carried out on days 2, 4 and 6.With EC, DAI increases for the entire day, MPO and TNFa increase in the lesion, ulcerative defect isfixed, neutrophil-lymphocytic infiltration increases, and TDI increases. When comparing the morphometric parameters of the alteration zone in EC under the conditions of vitamin D3 use, in contrast to the use of 5-ASA, a decrease in the number of lymphocytes, an increase in fibroblasts was revealed on day 2, a decrease in the number of plasmocytes and an increase in fibroblasts on day 4, an increase in the number of histiocytes and fibroblasts on day 6. The diameter of the ulcerative defect and the TDI index have no significant differences between the compared groups. When comparing the effectiveness of vitamin D3, in contrast to the use of 5-ASA, the MPO content is higher on day 6; the TNFa content is higher on day 4.In EC, the effects of using rectal suppositories with vitamin D3 on clinical signs, the size of the ulcerative defect, the content of MPO and TNFa in the lesion are comparable to the effects of using rectal suppositories with 50 mg of 5-ASA; more pronounced with respect to the dynamics of the cellular composition of the lesion of the colon.

Clinical outcomes for Clostridioides difficile associated diarrhea in inflammatory bowel disease patients versus non-IBD population: A retrospective cohort study.

Patients with inflammatory bowel disease (IBD) have a higher incidence of Clostridioides difficile infection (CDI). Previous studies have demonstrated negative clinical outcomes in IBD patients with CDI compared to patients without CDI. The clinical presentation of CDI is indistinguishable from IBD exacerbation, thus posing a frequent clinical dilemma on the role of Clostridioides infection in the testing, diagnosis, and treatment of these patients. To compare clinical outcomes of CDI in patients with IBD to those without IBD. Retrospective cohort of adult patients admitted to Rabin Medical Center Israel between the years 2014 and 2020 with a concurrent diagnosis of IBD and CDI. Matching 1:2 was performed between the IBD patients and the non-IBD population with respect to age and sex. Sixty-seven patients with IBD and 134 patients without IBD were included in the study. The groups' median age was 40.6 (interquartile range [IQR] of 29.8-68.9), with 45.8% male and 54.2% female. The non-IBD group had a higher Charlson score with 2 (IQR 0; 5) versus 0 (IQR 0; 4) in the IBD group (P value <.01). Patients with IBD had more exposure to systemic antibiotics, 71.1% versus 26.3% (P value <.01). In a multivariable analysis we found no difference in 90-day mortality and rate of relapse between the 2 study groups with an odds ratio of 1.709 (95% confidence interval 0.321-9.905) and odds ratio of 0.209 (95% confidence interval 0.055-1.513) respectively. In our cohort patients with IBD who present with diarrhea and concomitant CDI have similar rates of relapse and mortality compared with patients without IBD.

P579 Real-world comparison of effectiveness between tofacitinib and ustekinumab in patients with ulcerative colitis exposed to at least one anti-TNF agent: results from the TORUS study

Abstract Background We aimed to compare the effectiveness of tofacitinib and ustekinumab in patients with ulcerative colitis (UC) previously exposed to at least one anti-TNF agent. Methods In this multicenter study, we retrospectively included consecutive UC adult patients previously exposed to at least one anti-TNF agent, with partial Mayo score (pMS) &amp;gt; 2, having who started tofacitinib or ustekinumab between January 2019 and June 2022. The primary endpoint was steroid-free clinical remission (pMS ≤ 2) (CFREM) at week 16 (W16). Secondary endpoints were endoscopic remission (CFREM + Mayo endoscopic score (MES) ≤ 1), and histological remission (CFREM + MES ≤ 1 + Nancy index ≤ 1). Comparisons were performed using propensity score analyses adjusted on potential confounders. Results Overall, 289 patients were included (tofacitinib = 124 patients, ustekinumab = 165 patients). The groups were comparable (tofacitinib vs vedolizumab) for male gender (50.8% vs 43.3%), mean age (40.7 vs 42.9 years), median UC duration (8.6 vs 9.3 years), concomitant use of 5-ASA (13.7% vs 9.7%), steroids (25.0% vs 29.7%), immunosuppressants (7.3% vs 5.5%), and ≥ 2 prior biologics (85.5% vs 82.4%). Tofacitinib group had more pancolitis (55.6% vs 42.4%, p = 0.026) and UC with pMS &amp;gt; 6 (64.5% vs 50.3%, p = 0.016). In our study, 42.1 % of the patients treated with tofacitinib continued using a dose of 10 mgx2/day until W16 while 47.3% of the patients on ustekinumab required dose escalation to 90 mg/4 weeks before W16. After propensity score analysis, the rate of CFREM at W16 was 37.8% and 35.6% in the tofacitinib and ustekinumab arms, respectively arm (p=0.75). CFREM at W16 was achieved in 43.3% vs 57.1% (p = 0.48) after failure of one biologic, 20.7% vs 37.9% (p=0.16) two biologics and 46.7% vs 23.2% (p=0.047) or ≥ 3 biologics, in tofacitinib and vedolizumab arms, respectively. After primary failure to at least one biologic, the rate of CFREM at W16 was 46.3% on tofacitinib vs 25.9% on ustekinumab (p = 0.13). CFREM at W16 was similar with tofacitinib and ustekinumab in case of more severe UC such as pMS ≥ 6 (40.6% vs 41.5%) and CRP &amp;gt; 30 (27.2% vs 33.0%). No predictor of tofacitinib effectiveness has been identified. Factors associated with no CFREM at W16 on ustekinumab were male gender (p=0.035), ≥ 3 prior biologics (p=0.013), prior use of tofacitinib (p=0.03), primary failure to at least one biologic (p=0.013). Endoscopic remission was achieved in 17.0% vs 11.7% (p =0.47) and histological remission in 4.4% vs 7.8% (p=0.32) of the patients treated with tofacitinib and ustekinumab, respectively. Conclusion Tofacitinib and ustekinumab have similar effectiveness in UC after anti-TNF failure. However, the efficacy of ustekinumab could be more impacted by prior therapeutic failures.

P659 Continuing or stopping 5-aminosalicylate in patients with Inflammatory Bowel Disease under anti-TNF therapy: A nationwide population-based study

Abstract Background The clinical impact of continuing or stopping 5-aminosalicylate (5-ASA) after escalating to treatment with an anti-tumour necrosis factor (TNF) agent in patients with inflammatory bowel disease (IBD) is currently unclear. We aimed to compare the outcomes of IBD patients who stopped or continued 5-ASA after starting anti-TNF therapy. Methods We analysed data obtained from the Korean National Health Insurance claims database between 2007 and 2020. Our analysis included IBD patients already on 5-ASA treatment who started anti-TNF treatment. We compared the prognosis of patients who stopped 5-ASA within 90 days of anti-TNF initiation with those who continued 5-ASA. The primary outcome was any adverse clinical event defined as a composite of intestinal surgery, IBD-related hospitalization, or new corticosteroid use. Kaplan-Meier method and Cox proportional hazards models at landmark time were used to calculate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). Results Among 62,262 patients diagnosed with IBD during the study period, 7,442 patients were included for analysis. A total of 1,037 (13.9%) patients discontinued 5-ASA within 90 days of starting anti-TNF therapy (Figure 1). Among the included patients, 4,479 (60.2%) had Crohn’s disease, while 2,963 (39.8%) had ulcerative colitis (Table 1). Discontinuation of 5-ASA was not associated with an increased risk of any adverse clinical events, as well as its component outcomes of intestinal surgery, IBD-related hospitalization, and corticosteroid use, with aHRs of 1.011 (95% CI, 0.934 to 1.095), 0.954 (95% CI 0.760 to 1.198), 0.995 (95% CI 0.894 to 1.107), and 0.969 (95% CI, 0.890 to 1.056), respectively (Table 2). In addition, the cumulative incidence of each adverse clinical event, as well as the composite outcome, were not significantly different between the two groups (all, p &amp;gt; 0.05) (Figure 2). Subgroup analysis by sex, IBD type, the timeframe of anti-TNF use, pre-anti-TNF 5-ASA use duration, pre-anti-TNF corticosteroid use, pre-anti-TNF hospitalizations, pre-anti-TNF emergency department visits, and anti-TNF agent type also showed no significant difference in the development of adverse clinical events between the two groups. Conclusion In this nationwide population-based study, we observed that discontinuing 5-ASA after starting anti-TNF therapy was not associated with an increased risk of adverse clinical events.

P167 Ileocecal valve that cannot be intubated during colonoscopy in patients with Crohn’s disease: Is this a sign of poor prognosis?

Abstract Background In Crohn's disease (CD) the inability to intubate ileocecal valve during colonoscopy may be correlated with disease prognosis. We aimed to compare the long-term outcomes of CD patients with or without ileocecal valve intubation during colonoscopy to assess its value as a prognostic parameter. Methods Data were retrospectively collected in CD with isolated ileal involvement between January 1993 and July 2022. Patients who underwent ileal resection were excluded. Basal characteristics as well as long-term clinical outcomes including steroid dependence, CD-related hospitalization, biological treatment and abdominal surgery were compared between the two groups of patients with intubated and non-intubated ileocecal valve during colonoscopy. Results A total of 155 CD patients were included. Median age at disease onset was 35 years and 63.9% was male. Out of 155, 97 (62.5%) were in intubated and 58 (37.5%) were in non-intubated group. The median follow-up of cohort was 3.81 years (1.44-7.63). Non-intubated group was older at diagnosis (39.0 vs 30.5 age; p=0.002) while other baseline characteristics such as sex, smoking status, family history of IBD, disease duration, perianal disease, upper gastrointestinal and extraintestinal involvements were similar. At baseline, serum hemoglobin (12.3 vs. 13.3 mg/dL; p=0.029), albumin (4.1 vs. 4.3 g/dL; p=0.001), CRP (14 vs. 7.8 mg/L; p=0.005) and CDAI score (301 vs. 208; p&amp;lt;0.001) were all statistically significantly higher in the non-intubated group than in the intubated group. Non-intubated group had more frequent stenosing (41.4% vs. 10.1%) and penetrating (29.3% vs. 5.2%; p&amp;lt;0.001) disease course. On the other hand, intubated group had more inflammatory disease behavior (84.5% vs. 29.3%; p&amp;lt;0.001). Budesonide (37 vs. 13; p=0.043) and methotrexate use (32 vs. 9; p=0.017) was more common the intubated group, while 5-ASA, steroid, and thiopurine use was similar. Non-intubated group had higher rates of steroid dependence (67.2% vs. 46.4%; p=0.012), biologic treatment (89.7% vs. 58.8%; p&amp;lt;0.001), CD-related hospitalization (81% vs. 24.7%; p&amp;lt;0.001), and major abdominal surgery (58.6% vs. 15.5%; p&amp;lt;0.001). In logistic regression analysis, positive predictors of successful ileum intubation were inflammatory type CD (OR: 14.821), high serum albumin level (OR: 5.919), and older age (OR: 1.069), whereas negative predictors were stenosing (OR: 0.262) and penetrating (OR: 0.247) CD behavior. Conclusion In CD patients with isolated ileal involvement, the inability to intubate the ileocecal valve during colonoscopy may indicate a poor prognosis.

AMINOSALICYLATE USE IN PEDIATRIC PATIENTS WITH CROHN’S DISEASE

Abstract INTRODUCTION Societal guidelines recommend against the use of 5-aminosalicylate (5-ASA) therapy for pediatric patients with Crohn’s Disease (pCD). Previous trials showed no benefit of 5-ASAs for inducing remission and similar one-year relapse rates when compared with placebo. Conversely, biologics are recommended as first-line therapy due to higher remission rates, corticosteroid-sparing effects, and potential to alter disease progression. AIMS We aimed to describe the use of 5-ASAs in pCD and the associated patterns of biologic and corticosteroid use in a large multi-center patient cohort. METHODS We used data from the Biologic dISContinUation sTudy (BISCUIT), a multi-center study in which retrospective medical record abstraction from 7 US centers supplemented prospectively collected data from the ImproveCareNow (ICN) Network Registry. We included patients newly diagnosed with pCD (&amp;lt;18 years old) and compared patients who were prescribed a 5-ASA within 90 days of diagnosis to those who were not exposed to 5-ASAs. We used Student’s t-tests, chi-squared tests, and Wilcoxon rank sum to compare baseline characteristics, including demographics (age, gender, race, ethnicity, insurance status); disease characteristics (age at diagnosis, Paris classification, concomitant liver disease, extraintestinal manifestations); and disease activity measures (labs, disease activity indices, and extraintestinal manifestations). RESULTS Our study included 608 patients, 142 of whom (23.4%) were treated with 5-ASAs within 90 days after CD diagnosis. At baseline, younger patients (p&amp;lt;0.01), those with colonic disease (L2) (p=0.03), and those with Medicaid as their primary insurance (p=0.05) were more likely to receive 5-ASAs (Table 1). There was no difference in 5-ASA use by disease severity (p=0.52). Those on 5-ASA therapy had an 84-day longer delay in initiation of their first biologic medication, with 56.1% of patients starting a biologic at least 90 days after diagnosis (p&amp;lt;0.001). There were no differences in corticosteroid use (p=0.08) or dietary therapy (p=0.90) (Table 2). CONCLUSIONS We found 5-ASA use was common in pCD and was associated with a near 4-month delay in initiating biologic therapy. These results are a call-to-action to improve guideline dissemination and examine barriers such as insurance status in the evidence-based treatment of pCD. Our future work will evaluate differences in outcomes, biologic durability, and disease complication rates between these groups.

COVID-19 susceptibility and clinical outcomes in inflammatory bowel disease: An updated systematic review and meta-analysis.

The susceptibility, risk factors, and prognosis of COVID-19 in patients with inflammatory bowel disease (IBD) remain unknown. Thus, our study aims to assess the prevalence and clinical outcomes of COVID-19 in IBD. We searched PubMed, EMBASE, and medRxiv from 2019 to 1 June 2022 for cohort and case-control studies comparing the prevalence and clinical outcomes of COVID-19 in patients with IBD and in the general population. We also compared the outcomes of patients receiving and not receiving 5-aminosalicylates (ASA), tumour necrosis factor antagonists, biologics, systemic corticosteroids, or immunomodulators for IBD. Thirty five studies were eligible for our analysis. Pooled odds ratio of COVID-19-related hospitalisation, intensive care unit (ICU) admission, or death in IBD compared to in non-IBD were 0.58 (95% confidence interval (CI)=0.28-1.18), 1.09 (95% CI=0.27-4.47), and 0.67 (95% CI=0.32-1.42), respectively. Inflammatory bowel disease was not associated with increased hospitalisation, ICU admission, or death. Susceptibility to COVID-19 did not increase with any drugs for IBD. Hospitalisation, ICU admission, and death were more likely with 5-ASA and corticosteroid use. COVID-19-related hospitalisation (Odds Ratio (OR): 0.53; 95% CI=0.38-0.74) and death (OR: 0.13; 95% CI=0.13-0.70) were less likely with Crohn's disease than ulcerative colitis (UC). In conclusion, IBD does not increase the mortality and morbidity of COVID-19. However, physicians should be aware that additional monitoring is needed in UC patients or in patients taking 5-ASA or systemic corticosteroids.

S819 Non-Biologic Medication Use Pre- and Post-Ustekinumab Initiation Among Patients With Ulcerative Colitis

Introduction: Among patients with ulcerative colitis (UC), treatment with immunomodulators, 5-ASA (5-aminosalicylic acid), and corticosteroids while receiving biologic agents is common. However, real-world information on non-biologic medication use among UC patients initiated on ustekinumab is limited. This study compared non-biologic medication use pre- and post-ustekinumab initiation among UC patients. Methods: Adults with UC initiated on ustekinumab (index date) between 10/18/2019 (FDA approval of ustekinumab for UC) and 10/31/2020 were selected from the de-identified health insurance claims Symphony Health Solutions’ Patient Transactional Datasets. Patients were excluded if they had a claim for Crohn’s disease anytime or for other autoimmune diseases pre-index. Patients were required to have: ≥1 claim for UC in the 12 months pre-index period (baseline), ≥2 ustekinumab claims within 90 days of the index date, and ≥6 months of follow-up. Non-biologic agent use in the 6 months period before and after the initiation of ustekinumab was compared with a logistic model estimated by generalized estimating equation. Results were reported as odds ratio with 95% confidence interval and p-values. Results: A total of 760 patients with UC were initiated on ustekinumab and selected for the study (age 44.6 years old; 48.9% female; baseline biologic use 52.1% [potentially underestimated given the database open nature]; Quan-Charlson comorbidity index 0.62). The likelihood of immunomodulator and 5-ASA use decreased by 22% and 46%, after ustekinumab initiation (all P< 0.05). Similarly, patients were 52% less likely to use any corticosteroids and 34% less likely to use corticosteroids for ≥60 days (all P< 0.05). Further, there was no significant changes observed for the use of opioids (18.9% vs. 17.4%) or the use of anti-diarrheals (5.9% vs. 6.1%), and patients were 29% less likely to use GI antispasmodics after ustekinumab initiation (P< 0.05; Table). In a descriptive analysis, corticosteroids use numerically decreased at each month post-ustekinumab from 25.4% during the first 30 days following the index date compared to 17.4% within 150-180 days post-ustekinumab (Figure). Conclusion: In this real-world study of patients with UC, initiating ustekinumab was associated with a significant decrease in the use of immunomodulators, 5-ASA, and corticosteroids. Longer-term data are necessary to better understand non-biologic medication use after biologic initiation and inform treatment choice for patients with UC.Figure 1.: Corticosteroid use during the 6 months post-ustekinumab initiation (N=760). Table 1. - Non-biologic medication use in the 6-month period before vs after the initiation of ustekinumab Pre-ustekinumab Post-ustekinumab Odds ratio1 (95% CI), p-value N = 760 Use of immunomodulators 120 (15.8) 97 (12.8) 0.78 (0.64, 0.95), 0.014* Use of 5-ASA 312 (41.1) 208 (27.4) 0.54 (0.47, 0.62), < 0.001* Use of corticosteroids 481 (63.3) 346 (45.5) 0.48 (0.41, 0.57), < 0.001* Cumulative use2 ≥60 days 243 (32.0) 180 (23.7) 0.66 (0.55, 0.79), < 0.001* Cumulative use2 ≥90 days 151 (19.9) 114 (15.0) 0.71 (0.58, 0.87), 0.001* ≥1 episode3 ≥ 60 days 201 (26.4) 156 (20.5) 0.72 (0.59, 0.87), < 0.001* ≥1 episode3 ≥ 90 days 118 (15.5) 89 (11.7) 0.72 (0.56, 0.93), 0.013* Use of opioids 144 (18.9) 132 (17.4) 0.90 (0.74, 1.10), 0.296 Use of antidiarrheals 45 (5.9) 46 (6.1) 1.02 (0.76, 1.38), 0.879 Use of GI antispasmodics 86 (11.3) 63 (8.3) 0.71 (0.54, 0.93), 0.013* Abbreviations: CI: Confidence interval; GI: Gastrointestinal; 5-ASA: 5-aminosalicylic acid Notes: (1) Odds ratio obtained from a logistic model estimated with generalized estimating equation; (2) Non-overlapping days of supply included; (3) A therapy exposure gap of 14 days of supply was used to define continuous use

Clinical and endoscopic outcomes of patients with colonic Crohn's disease treated with 5-aminosalicylates as monotherapy

BackgroundIn spite of the lack of evidence regarding the clinical benefits of oral 5-aminosalicylic acid (5-ASA) compounds in Crohn's disease (CD), these drugs are frequently used in daily clinical practice, particularly for colonic CD. Our aim is to assess the use and clinical outcomes of 5-ASA of those patients with colonic CD treated with 5-ASA as monotherapy. MethodsPatients diagnosed with isolated colonic CD and treated with 5-ASA but never exposed to immunosuppressants or biologicals were identified from the local databases of five referral centres. A retrospective review of clinical and endoscopic outcomes was performed. ResultsOut of 545 patients with isolated colonic CD, 106 (19%) were treated with oral 5-ASA in monotherapy as maintenance therapy. The median follow-up was 144 months (interquartile range [IQR], 48–234). Almost all of the patients (92%) presented an inflammatory pattern and 11% developed perianal disease. Half of the patients had already received 5-ASA at diagnosis, and the median duration of 5-ASA treatment was 107 months (IQR 22.5–187). Endoscopic remission, as defined by the absence of ulcers at the last complete colonoscopy, was observed in 65% of those patients undergoing at least one colonoscopy during follow-up. Male gender and extraintestinal manifestations were associated with a lower likelihood of achieving endoscopic remission. Nine patients required colectomy, but mostly soon after CD diagnosis. Conclusions5-ASA seems to be of benefit in the long-term in one fifth of patients with colonic CD as the only maintenance therapy and should be considered in fragile patients with Crohn's colitis.

Abstract P001: Repurposing A Drug Targeting Inflammatory Bowel Disease For Lowering Hypertension

Both the gut per se and its residents, the gut microbiota are linked to blood pressure (BP) regulation, whereby, the gut can be recognized as a previously neglected target organ for hypertension. Hypertension and gut diseases such as inflammatory bowel disease (IBD) share commonalities of host inflammation in the gut and microbiota dysbiosis. Therefore, we reasoned that current treatments to remedy gut inflammation and dysbiosis in IBD could be repurposed to ameliorate hypertension. IBD is commonly treated with 5-Aminosalicylic acid (5-ASA, Mesalamine), which is a selective PPAR-γ agonist to prevent gut inflammation. Clinical use of 5-ASA is also reported to ameliorate gut dysbiosis in IBD. Based on this premise, in this study we chose to test our hypothesis that 5-ASA is an antihypertensive drug owing to its dual ability to enhance PPAR-γ in the gut and to correct gut dysbiosis. 2 groups of 11-12 weeks old male genetically hypertensive Dahl salt-sensitive (S) rats were radiotelemetrically monitored for BP, and orally gavaged with (n=9) or without (n=7) 5-ASA (150 mg/kg) for 4 weeks. PPAR-γ expression was assessed by RT-qPCR. Fecal microbiota were profiled by 16S gene sequencing. Lastly, for translational significance, F/B ratio of non-IBD (n=611) patients was compared with that of IBD (n=631) patients in the American Gut Project data for their Firmicutes/Bacteroidetes (F/B) ratio, elevation of which is a marker of gut dysbiosis. 5-ASA significantly lowered BP of the S rat (mean BP without 5-ASA, 153±1 mm Hg; mean BP with 5-ASA, 145±1 mm Hg, P &lt;0.0001). PPAR-γ gene expression was significantly higher in proximal colon, but not in the heart or kidney. In addition, treatment with 5-ASA corrected gut dysbiosis as observed by a significant reduction in the F/B ratio compared to control. In accordance, humans without IBD had a similar lower F/B ratio, which was consistent with the data presented here comparing S rats with 5-ASA. Collectively, these data support our hypothesis that 5-ASA, an FDA-approved anti-IBD drug, could be repurposed to treat hypertension by specifically enhancing the gut PPAR-γ mediated anti-inflammatory effect while also correcting microbiota dysbiosis to lower BP.

The safety of paternal and maternal use of 5-aminosalicylic acid during conception and pregnancy: a nationwide cohort study.

Data on the safety of paternal use of 5-aminosalicylic acid (5-ASA) prior to conception are lacking, and the safety of maternal use of 5-ASA during pregnancy has not been examined in nationwide data. To examine offspring outcomes after paternal pre-conception use of 5-ASA, and after maternal use during pregnancy METHODS: This nationwide cohort study was based on Danish health registries. The study population included live born singletons of patients with ulcerative colitis (UC) or Crohn's disease (CD). Paternal exposure included 2168 children fathered by men treated with 5-ASA, and 7732 unexposed. Maternal exposure included 3618 children exposed in utero to 5-ASA, and 7128 unexposed. The outcomes were pre-term birth, small for gestational age (SGA), low Apgar score and major congenital abnormalities (CAs) according to EUROCAT guidelines. The vast majority of fathers and mothers used mesalazine. In children fathered by men with UC using 5-ASA, we found no increased risk of pre-term birth, SGA or low Apgar score. The hazard ratio (HR) of CAs was 1.30 (95% CI 0.92-1.85). In children of fathers with CD, the odds ratio (OR) of SGA was 1.52 (95% CI 0.65-3.55). After maternal 5-ASA exposure, the OR of SGA in children of women with UC was 1.46 (95% CI: 0.93-2.30); for CAs in children of women with CD, HR was 1.44 (95% CI 0.84-2.47). Paternal and maternal use of 5-ASA was safe across offspring outcomes; none of the findings reached statistical significance. The safety of 5-ASA formulations that are used infrequently cannot be settled here.