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Abstract Background The Middle East is experiencing a rapid increase in inflammatory bowel disease (IBD) likely due to urbanization, dietary changes and environmental factors. The region lacks sufficient data, making it challenging to comprehend the full extent of IBD's impact on healthcare systems. This research aims to investigate IBD trends, disease behaviour, evolution and persistence of advanced therapy (AT) within a predominantly Arab patient population in UAE. Methods This observational study at a tertiary IBD centre in the UAE utilized the local IBD registry (prospective data collection from 2022). Data included disease characteristics, and AT usage. Descriptive statistics, regression models and Kaplan-Meier analysis were employed. Results Of the 859 IBD patients treated from 2012 to 2024, comprehensive data were available for 321 patients under active follow-up of which 64.2% comprised of Crohn’s disease (CD) and 35.8% with ulcerative colitis (UC). A ten-fold rise over a 22-year period in new diagnoses of IBD, particularly CD was observed. Median age at diagnosis was 25 years (IQR 25-42), with CD patients younger (24 years) than UC patients (28 years). Within CD, 20% had stricturing, 17% penetrating and 36% with perianal disease. 85% of CD and 61% of UC patients were exposed to at least one AT; 25% of CD and 18% of UC patients >2 ATs, and 16% of CD and 11% of UC >3 ATs. Infliximab and adalimumab were the main first-line ATs, while ustekinumab and risankizumab used in later AT lines. Ustekinumab and risankizumab, showed higher AT persistence compared to anti-TNFs. In CD, stricturing disease (p<0.05), penetrating disease (p<0.01), longer disease duration (p<0.05), and younger age at diagnosis (p<0.05) were linked to higher exposure to AT lines. In UC, younger age at diagnosis (p=0.001) was associated with increased number of AT exposures. Use of AT significantly changed between 2017–2020 and 2021–2024 (p<0.001). Infliximab, adalimumab and vedolizumab were initially the most prevalent, with ustekinumab, risankizumab, and upadacitinib usage rising substantially by 2022. The time to initiate AT for CD and UC following diagnosis decreased significantly since 2017 by 6.82 and 6.91 months per year, respectively (p<0.001), with a combined median time of 2.46 months (IQR 4.8) for CD for 2023-2024. Conclusion This is the first comprehensive evaluation of IBD in the UAE, highlighting a significant rise in new diagnoses, particularly CD with aggressive phenotypes, reflecting broader regional trends. AT utilization has evolved, with ustekinumab and risankizumab demonstrating better persistence and increasing adoption. These insights into disease patterns will help inform future regional healthcare policies.

Abstract Background Iron deficiency is common in patients with inflammatory bowel disease (IBD), where poor absorption or prior surgery often renders oral iron supplementation ineffective, necessitating intravenous (IV) iron therapy. Hypophosphataemia, particularly associated with ferric carboxymaltose via fibroblast growth factor 23 dysregulation, is a recognized complication of IV iron therapy. It can result in severe outcomes such as rhabdomyolysis, osteomalacia, fractures, and convulsions. This study evaluates the risk of hypophosphataemia between ferric carboxymaltose and other IV iron formulations and its association with complications. Methods This retrospective propensity-matched study utilised the TriNetX database, a global repository of de-identified electronic health records. The first analysis compared ferric carboxymaltose to other IV iron formulations (iron sucrose, sodium ferric gluconate, ferumoxytol, ferric derisomaltose), matched on demographics (age, gender, ethnicity) and comorbidities (vitamin D deficiency, malnutrition, malabsorption, diabetes, CKD by stage, alcohol abuse, hyperparathyroidism, corticosteroid, diuretic, antacid, and bisphosphonate use) to assess hypophosphataemia risk. The second and third analyses evaluated hypophosphataemia-related complications in ferric carboxymaltose versus other formulations, both in the general population and in patients with IBD. Results We compared 115,242 ferric carboxymaltose patients to those on other IV iron formulations. Ferric carboxymaltose was associated with higher odds of severe (OR: 2.84, 2.22–3.64, p<0.0001) and moderate (OR: 1.37, 1.29–1.46, p<0.0001) hypophosphataemia but lower odds of mild hypophosphataemia (OR: 0.84, 0.79–0.88, p<0.0001). Among 25,586 hypophosphataemic patients, those on ferric carboxymaltose had lower odds of acute complications within 3 months, including muscle weakness (OR: 0.57, 0.47–0.70, p<0.0001), rhabdomyolysis (OR: 0.38, 0.20–0.75, p=0.003), disorientation (OR: 0.53, 0.46–0.61, p<0.0001), convulsions (OR: 0.59, 0.48–0.73, p<0.0001), cardiac arrhythmias (OR: 0.61, 0.54–0.69, p<0.0001), and respiratory failure (OR: 0.57, 0.50–0.64, p<0.0001). Over 2 years, chronic complications such as osteomalacia and fractures (23,508 patients each) showed no differences. In patients with IBD, no significant differences were observed in acute (2,688 each) or chronic complications (2,541 each) between cohorts. Conclusion Ferric carboxymaltose was linked to higher odds of severe and moderate hypophosphataemia but fewer acute complications than other IV iron formulations. The reasons for these differences remain unclear and warrant further research to understand the relationship between IV iron, hypophosphataemia, and clinical outcomes.

Abstract Background Vedolizumab (VDZ) is a gut selective, monoclonal anti-α4β7 integrin antibody approved for the treatment of moderately to severely active ulcerative colitis (UC) or Crohn’s disease (CD) and is available in subcutaneous (SC) formulation. This analysis assessed the long-term safety outcomes of specific interest to the SC formulation of VDZ. Methods Patients (pts) who participated in VISIBLE 1 or VISIBLE 2 were eligible to enrol in VISIBLE OLE (NCT02620046). In VISIBLE 1, pts with UC were treated with placebo, VDZ SC or VDZ intravenous (IV). In VISIBLE 2, pts with CD were treated with placebo or VDZ SC. In VISIBLE OLE, pts received VDZ SC 108mg every 2 weeks (Q2W) or weekly. Pts received training on SC administration, and most injections were conducted at home by pt or caregiver. Safety of VDZ SC included assessing anti-VDZ antibody (AVA) status and injection site reaction (ISR) adverse events. Blood specimens for AVA assessment were collected 30 minutes before dosing every 16 weeks, at the final dose and the final safety visit 18 weeks after last dose. Data were assessed by treatment pts received during VISIBLE 1 and 2. Results Overall, 288 pts with UC and 458 pts with CD enrolled in VISIBLE OLE. A mean of 91.1 and 74.2 SC injections were completed by pts with UC and CD, respectively, during the OLE. Among pts with UC, the positive AVA rate was higher in pts previously treated with placebo (17.3%) than those treated with VDZ SC (3.4%) or IV (2.6%) (Table 1). The positive AVA rate was also higher among pts with CD previously treated with placebo (11.4%) than with VDZ SC (1.8%). A total of 14/288 pts (4.9%) with UC reported ISRs (Table 2), most of which were mild and none were serious. Two pts developed moderate ISRs; neither required dose modification and both were resolved. Overall, 19/458 pts (4.1%) with CD reported ISRs (Table 2). The majority of ISRs were mild, 2 were moderate and none were severe, and none required dose modification. No direct correlation between AVA status and ISRs was identified, with 11/14 pts (78.6%) with UC and 17/19 pts (89.5%) with CD who reported ISRs being AVA negative. All 5 pts who were AVA positive and reported an ISR had previously received placebo. The highest rate of ISRs were in pts who received placebo in VISIBLE 1 (13.5%). Conclusion No new long-term safety events were identified with the VDZ SC route of administration compared to IV, except for ISRs. A higher proportion of patients who had previously been treated with placebo than those treated with VDZ during VISIBLE 1 and 2 were AVA positive during VISIBLE OLE, supporting a benefit of continued therapy with VDZ SC after IV induction, rather than cessation of treatment for a period of time.

Abstract Background The STRIDE-II recommendations highlighted the importance of targeting objective measures of disease control, including endoscopic healing, in patients (pts) with ulcerative colitis (UC).1 Risankizumab (RZB), an interleukin-23 specific inhibitor, showed improvement in the outcomes of clinical remission and endoscopic improvement compared to placebo in pts with moderately-to-severely active UC.2 Visualizing the changes of endoscopic scores from induction and maintenance may provide insight into pt disease course during treatment. Thus, this analysis sought to provide an overview of change in endoscopic scores of pts enrolled in UC clinical studies. Methods Using individual pt data from the Phase 2b/3 studies of RZB in UC, changes in Mayo endoscopic scores in induction and maintenance were assessed. For induction, pts received either intravenous (IV) placebo (PBO) or RZB for 12 weeks (wks). Pts from the Phase 2b and Phase 3 INSPIRE studies who had a clinical response to induction treatment were rerandomized into the maintenance study [COMMAND] and received subcutaneous PBO (withdrawal), RZB 180 mg, or RZB 360 mg every 8 wks for 52 wks. To be eligible for INSPIRE, pts had to have a baseline (BL) Mayo endoscopic score of 3 or 2 confirmed by central review. For this analysis, endoscopic scores are reported for induction BL and wk 12 and maintenance BL and wk 52 for each treatment. "Endoscopic improvement" was defined as a score of 1 or 0 at the time of follow-up. Results Among pts with a Mayo endoscopic score of 3 at induction BL, 28% achieved endoscopic improvement after 12-wk treatment with RZB 1200 mg; 57% of pts with a BL score of 2 showed endoscopic improvement (Fig. 1). In contrast, among PBO-treated pts with a score of 3 or 2 at BL, 11% and 18%, respectively, achieved endoscopic improvement after induction. Most PBO-treated pts (63%) had no score change at wk 12. During the maintenance study, 29%–35% of pts in the RZB treatment groups had an endoscopic score of 2 or 3 at maintenance BL. (Fig. 2). For those with a BL score of 3, most pts receiving RZB 360 mg achieved endoscopic improvement (62%); similarly, 65% of those with a BL score of 2 showed endoscopic improvement at wk 52. Trends were similar for RZB 180 mg with ≥80% of pts with a BL score of 1 or 0 maintained a 1 or 0 through wk 52. Among PBO-treated pts, ≥60% maintained a score of 3 or 2 from maintenance BL to wk 52; approximately one third of pts’ scores improved to 1 or 0. Conclusion This analysis showed that RZB treatment improved endoscopic outcomes from wk 0 to wk 12 of induction and wk 0 to wk 52 of maintenance. These findings may help inform treatment expectations and shared decision-making for pts with UC initiating RZB treatment. References 1.Turner D, et al. Gastroenterology. 2021;160(5):1570-1583. 2.Louis E, et al. JAMA. 2024;332(11):881-897.

Abstract Background Risankizumab, an IL-23 inhibitor, has shown efficacy in RCTs and real-world studies for inducing and maintaining clinical remission in Crohn’s disease (CD) patients. We report the largest real-world evidence from the Middle East evaluating risankizumab’s effectiveness and safety in advanced therapy (AT) naive and exposed patients along with outcomes following dose intensification. Methods A prospective observational study in an Emirati cohort at tertiary IBD center in UAE evaluated clinical outcomes at induction (3-5 months) and maintenance (12-14 months), assessing clinical remission (CDAI <150), clinical response (CDAI improvement by 100 points) and endoscopic response (≥50% SES-CD improvement). Long-term outcomes following dose intensification were recorded for patients with inadequate or loss of response after 12 months. Continuous variables were reported using descriptive statistics, and predictors of clinical remission were identified using logistic regression. Results A total of 37 patients treated with risankizumab were included in the analysis of which 35.1% were AT naive, and 64.9% had prior AT exposure. The median age was 33 years (IQR 26-42) and the median follow-up was 7.5 months (IQR 4.5-16.5). AT-naive patients initiated risankizumab at a median of 31 days from diagnosis (IQR 31-61). Post-induction clinical remission was achieved in 43.2% (16/37), with higher remission observed in AT-naive patients (53.8%) compared to AT-exposed patients (37.5%). Clinical response during induction was observed in 89.2% of the total cohort, with 92.3% response in the AT-naive group and 87.5% in the AT-exposed group. Of the patients with a follow up period of >12 months, clinical remission and response was achieved in 60% (9/15) and 93.3% (14/15) of the total cohort respectively. Endoscopic response was achieved in 81.8% (9/11) of patients undergoing colonoscopy between 8 and 12 months. Prior AT exposure significantly reduced the odds of achieving clinical remission (p<0.05). Age, perianal disease, baseline Hb, albumin, CRP, CDAI, SES-CD, and prior ustekinumab exposure did not affect odds of remission. Response was re-captured in 4/6 patients with secondary loss of response following 4-weekly dose intensification. No adverse events were observed during the follow-up period. Conclusion Risankizumab was highly effective for Crohn’s disease in an Emirati cohort, especially in AT-naive patients with a short time from diagnosis to treatment. High endoscopic response was noted, and dose intensification frequently restored response in patients with a secondary loss. Prior advanced therapy exposure correlated with lower remission rates, highlighting the importance of early targeted intervention.

Abstract Background There is limited data on the clinical effectiveness of upadacitinib (UPA), an oral selective inhibitor of Janus kinase 1 (JAKi), in patients with perianal Crohn's disease (pCD). The objective of this study was to evaluate the real-world effectiveness of UPA in pCD. Methods This retrospective analysis utilized data on adults (>17 years) who initiated UPA at 45 mg/day for active pCD across 10 centers in the United States and Canada. Standardized data extraction and entry protocols were followed. The primary outcome was clinical response, defined as a ≥3-point reduction in Perianal Disease Activity Index (PDAI) between baseline and follow-up. Secondary outcomes included normalization of CRP (<5 mg/L) or hsCRP (<1 mg/L), clinical remission (PDAI ≤4), and rates of hospitalization, antibiotic use, corticosteroid initiation, and new pCD-related surgeries. Fistula healing on MRI pelvis fistula protocol was defined as an absence of T2-weighted hyperintensity and post-contrast enhancement on T1-weighted images. Predictive analyses used Cox proportional hazards models to evaluate baseline factors influencing time to PDAI remission, including BMI, CRP, albumin, PDAI, pCD disease duration, Montreal location and prior biologic exposure (<2 vs 2+). Results A total of 81 patients were treated with UPA for pCD (median age 35 years and 54.3% male). Most had ileocolonic disease (65.4%), with 54% presenting with complex fistulas. Of these, 92.6% had prior anti-TNF exposure, and 91 (88.9%) had prior exposure to 2+ biologics (Table 1). During a median follow-up of 4 months, clinical response (PDAI) was achieved in 17.3%. Improvement was observed in pain and restriction of activities (27.2%), restriction of sexual activity (13.6%), reduction in number of fistulas (11.1%), degree of induration (11.1%), and discharge (35.8%). Median CRP reduction was 21.05% [IQR: 0.00–74.53], and 21.0% achieved a ≥50% reduction in CRP. MRI healing was limited to 17.7% (6/34). Proctitis decreased from 23.5% at baseline to 7.4% at follow-up. During follow-up, hospitalizations occurred in 9.9%, 14.8% required antibiotics, 8.6% underwent examination under anesthesia in 8.6%, seton placement in 6.2%, and abscess drainage in 6.2%. Patients with ileocolonic disease showed the highest remission (54%) and response (15%) rates, while MRI healing was limited across all Montreal locations (7.4%). Lower baseline CRP (p < 0.05) and PDAI scores (p < 0.01) predicted shorter time to remission. Number of prior biologic exposures (p =0.2) and Montreal location (p = 0.7) were not predictive of time to PDAI remission (Figure 1). Conclusion UPA in a real-world cohort is effective in the management of treatment-refractory pCD. Randomized trials are needed to confirm these observations.

Abstract Background Vedolizumab (VDZ) is a gut selective, monoclonal anti-α4β7 integrin antibody approved for the treatment of moderate to severe ulcerative colitis (UC) or Crohn’s disease (CD). The subcutaneous (SC) formulation of VDZ was evaluated during the Phase 3 VISIBLE 1 and 2 studies. We report the long-term efficacy among patients (pts) with UC or CD treated with VDZ SC in the VISIBLE open-label extension (OLE) study. Methods Pts with UC or CD in VISIBLE 1/2 could enrol in VISIBLE OLE (NCT02620046). Pts in VISIBLE 1/2 who completed 52 weeks(W) of treatment with VDZ or placebo (randomised completers) and pts without clinical response at W6 who responded at W14 (non-randomised responders) received VDZ SC 108mg every 2W (Q2W) in the OLE. Pts with worsening disease were escalated to QW dosing. Clinical remission (partial Mayo score ≤2, no subscore >1 in UC; HBI score ≤4 in CD) up to W168 was assessed (pts with missing data or escalated to QW dosing were imputed as non-response, irrespective of clinical status). The number of pts who regained clinical response when escalated to QW dosing was also assessed. Results were summarized by prior VISIBLE 1/2 treatment groups. Results Data from 231 pts with UC and 344 pts with CD were included. In pts with UC, baseline OLE clinical remission rates were 55.0%, 91.3% and 77.1% among randomised completers (N=124) previously treated with placebo, VDZ SC and VDZ IV in VISIBLE 1, respectively. At W168, 40.0%, 56.5% and 62.9%, respectively, were in clinical remission on Q2W dosing. In non-randomised responders with UC (N=107), 57.0% were in clinical remission at baseline and 29.9% at W168 (Figure). In pts with CD, baseline OLE clinical remission rates were 60.3% and 62.0% among randomised completers (N=226) previously treated with placebo and VDZ SC in VISIBLE 2. At W168, 32.4% and 37.3% were in clinical remission on Q2W dosing. In non-randomised responders with CD (N=118), 57.6% were in clinical remission at baseline and 27.1% at W168 (Figure). In pts with UC escalated to QW dosing, 22.2% and 38.1% achieved clinical remission and response at W8 after transitioning to QW. Among pts with CD escalated to QW dosing, 38.6% and 53.5% achieved clinical remission and response by W8 after transitioning to QW. Higher rates of remission and response were noted in VDZ completers than non-randomised responders. No new long-term safety signals were noted with VDZ SC vs IV, except for injection site reactions. Conclusion The clinical benefit of VDZ SC was maintained long-term during VISIBLE OLE. A subset of pts who escalated to QW dosing regained response. Findings support VDZ SC as a treatment option for patients with UC or CD who require long-term maintenance therapy.

Abstract Background Upadacitinib (UPA) is an oral selective Janus kinase inhibitor approved for the management of moderate-to-severe Crohn’s disease (CD). One in ten CD patients may need a permanent ostomy (colostomy or ileostomy) during their disease course, and this may impact the efficacy of UPA, given its extended-release formulation. However, there is no data available in this population since patients with an ostomy are excluded from registrational CD trials. This study addresses this gap by comparing the real-world clinical effectiveness of UPA in CD patients with and without ostomy. Methods This retrospective cohort study analyzed data from the TriNetX US Collaborative Network of sixty-eight tertiary institutions, to examine adult (≥18 years) CD patients treated with UPA from May 19th, 2023 (FDA approval date) to October 31st, 2024. Patients were categorized based on presence or absence of an ostomy during the previous 5 years, after exclusion of patients with rheumatologic disease indications for UPA usage. A 1:1 propensity score matching (PSM) was performed to balance cohorts on demographics, baseline comorbidities, and CD severity indicators (CD phenotype, extraintestinal manifestations, concurrent corticosteroid and other biologics usage, hemoglobin, and body weight). Cox proportional hazards model estimated hazard ratios (HRs) in matched cohorts for clinical effectiveness as a composite outcome (corticosteroid use, hospitalizations, emergency room visits) and secondary individual outcomes, at one year post-treatment, with a significance threshold set at p < 0.05. Results The study sample of CD patients on UPA included 170 with and 1,428 without a prior ostomy. There were 144 patients in each cohort after PSM. Baseline characteristics of the cohorts are shown in Figure 1. After PSM (Figure 2), there were no significant differences between patients with CD on UPA, with and without prior ostomy, for composite outcomes (HR 0.93, p = 0.64), corticosteroid use (HR 0.78, p = 0.18), hospitalizations (HR 1.13, p = 0.64), or emergency room visits (HR 0.99, p = 0.97). Additionally, no significant differences were observed in opioid use (HR 0.95, p = 0.76), switch to another advanced therapy (HR 1.62, p = 0.06), or elevated biomarkers, including CRP (>10 mg/L, HR 1.00, p = 0.99) and fecal calprotectin (>150 µg/g, HR 0.85, p = 0.63) at the 1-year follow-up. Conclusion In CD patients, UPA demonstrated similar effectiveness for clinical outcomes of corticosteroid use, hospitalizations, emergency room visits and other secondary outcomes, regardless of their ostomy status.

Abstract Background Vedolizumab (VDZ) is a gut selective, monoclonal anti-α4β7 integrin antibody approved for the treatment of moderately to severely active ulcerative colitis (UC) or Crohn’s disease (CD). The subcutaneous (SC) formulation of VDZ was evaluated during the Phase 3 VISIBLE 1 and 2 studies. This analysis reports hospitalisations and surgeries among patients (pts) with UC or CD treated with VDZ SC enrolled in the VISIBLE open-label extension (OLE) study. Methods Pts who participated in VISIBLE 1 or VISIBLE 2 were eligible to enrol in VISIBLE OLE (NCT02620046) and received VDZ SC 108mg every 2 weeks (Q2W) or weekly. Patients were grouped according to their scenario in VISIBLE 1/2: Pts who withdrew between week (W) 6 and W52 (Scenario 1); pts who completed 52 weeks of treatment with VDZ or placebo (Scenario 2); pts without a clinical response at W6 but who responded at W14 and were not randomised (Scenario 3). The proportions of patients who experienced UC or CD related hospitalisation and/or surgery during VISIBLE OLE were assessed by scenario and treatment received during VISIBLE 1/2. Results A total of 288 pts with UC and 458 with CD enrolled in the VISIBLE OLE. The mean (min., max.) duration of VDZ exposure during VISIBLE OLE was 1276.7 days (127, 2577 days) among pts with UC and 1110.0 days (127, 2770 days) among pts with CD. The proportions of pts who had a UC or CD related hospitalisation or surgery during VISIBLE OLE are displayed in Table 1. Across all scenarios, a total of 8.3% (24/288) of pts with UC had a related hospitalisation. In total, 3/288 pts (1.0%) with UC (from Scenarios 1 and 3) had a colectomy. No pts with UC from Scenario 2 had a colectomy. Among pts with CD, a total of 13.1% (60/458) had a related hospitalisation. A total of 19 pts (4.1%) with CD had bowel surgery. Higher rates of IBD related hospitalisations and surgeries were observed in Scenario 1, both in pts with UC and with CD. Conclusion Findings from VISIBLE OLE showed that few pts with UC and CD treated with long-term VDZ SC required IBD related hospitalisations over the course of the study. Notably, very few patients with UC or CD required colectomies or bowel surgery.