Drug Persistence Research Articles

P0638 Impact of immunogenicity on 2-year clinical outcomes in patients with moderate-to-severe Crohn’s disease treated with subcutaneous infliximab: A post hoc analysis of the Phase 3 LIBERTY-CD study

Abstract Background Development of anti-drug antibodies (ADA) is a marker for negative long-term outcomes in patients (pts) with Crohn’s disease (CD) treated with biologics.1,2Post hoc analysis of the Phase 3 LIBERTY-CD study suggested that ADA occurrence did not have an overall impact on drug persistence and clinical efficacy of subcutaneous (SC) infliximab (IFX), despite leading to lower serum IFX levels.3 The current study evaluated the long-term impact of immunogenicity on clinical outcomes up to Week (W) 102 in pts who received IFX SC maintenance treatment. Methods This analysis included W10 responders to induction therapy with intravenous IFX, who were randomised to the IFX SC arm in the LIBERTY-CD study. ADAs were measured using a highly sensitive, drug-tolerant electrochemiluminescent affinity capture elution assay. Pts were divided into two groups according to ADA occurrence (ADA-positive, ≥1 ADA-positive sample any time after treatment initiation; ADA-negative, no ADA-positive samples throughout the treatment). Groups were balanced using propensity score matching (PSM) with a 2:1 ratio. Drug persistence, efficacy outcomes and serum IFX levels were compared between ADA-positive and ADA-negative pts at or up to W102. Results Among the 231 pts randomised to the IFX SC arm, baseline differences in age, weight, body mass index (BMI) and prior exposure to biologics and/or Janus kinase inhibitors (JAKi) were seen between ADA-positive and ADA-negative groups. Following PSM by BMI and prior exposure to biologics and/or JAKi, baseline characteristics were balanced between the ADA-positive (n=105) and ADA-negative (n=58) groups (Table). Drug persistence was comparable between ADA-positive and ADA-negative pts up to W102 (log-rank p=0.32; Figure). There were no significant differences in the proportion of pts achieving efficacy outcomes at W102 between ADA-positive and ADA-negative groups (clinical remission: 57.1% vs 46.6%, respectively, p=0.2510; endoscopic response: 40.0% vs 50.0%, respectively, p=0.2497). Mean serum IFX levels were higher in ADA-negative pts (14.9–20.6 µg/mL) than ADA-positive pts (11.5–13.9 µg/mL) throughout the maintenance phase. Despite no difference in drug persistence and clinical remission rates, pts who had an ADA titre ≥1,000 during maintenance therapy had a lower rate of endoscopic response at W102 compared to ADA-negative pts (8.3% vs 50.0%). Conclusion ADA occurrence did not have a significant impact on drug persistence of IFX SC up to W102. Drug levels were lower in ADA-positive than ADA-negative pts, but stable throughout the study in both groups. ADA titres may be relevant to long-term efficacy. Further study of ADA titres is warranted to identify thresholds that may impact long-term outcomes.

P0721 Anti-TNFs have similar safety profile to vedolizumab and ustekinumab as first line biologic treatment in elderly patients with Crohn’s disease

Abstract Background The prevalence of Crohn’s disease (CD) in elderly patients is rising and is associated with aging-related challenges. Data on effectiveness and safety of first line biologic treatment (FLBT) in the elderly, are scarce. Our aim was to compare the safety, effectiveness, and drug persistence to FLBT in elderly patients with CD. Methods A retrospective, single tertiary center study, including all patients with CD who initiated their FLBT at age≥60 years, between 1/1/2010 to 31/12/2023. Clinical and demographic data were extracted and adverse events (AEs), treatment response and drug persistence were collected. Results A total of 214 patients with CD ≥60 years of age started FLBT, data were available for 168 (78.5%) patients. Anti-TNFs were initiated in 85 (50.6%) patients, and non anti-TNFs in 83 (49.4%) patients (71-vedolizumab, 12-ustekinumab). Patients starting anti-TNF were younger (67.3±6.1 vs 72.0±7.0 years, p<0.001), with lower Charlson comorbidity index (CCI: 3.6±1.7 vs 4.9±2.2, p<0.001), had higher rates of penetrating (31.8% vs 9.6%, p=0.002) and perianal (40.0% vs 18.1%, p=0.002) disease phenotype, and previous GI resections (37.6% vs 22.9%, p=0.038). Endoscopic disease severity was comparable [Table 1]. Drug persistence was calculated from 2014 (time of vedolizumabs’ approval for clinical use) and was similar between the groups (60 patients on anti-TNF: median 82.0 weeks [IQR 27.5-175.3] vs. 83 patients on non-anti-TNF median 89.7 weeks [IQR 41.0-183.9], p=0.765). Use of corticosteroids (CS) and immunomodulators (IMM) during 14-weeks of induction and 52-weeks of maintenance was comparable (p=NS). At 52-weeks, no difference was observed in clinical response and remission rates, nor in dose escalation and drug discontinuation rates (p=NS). Eighty-three AEs were recorded at 52-weeks: 50 (58.8%) in anti TNF vs. 33 (39.8%) in non-anti-TNF group. Serious infections: 7 (8.2%) patients in the anti-TNF group (3 hospitalized for sepsis: 1 urinary and 2 respiratory, 1 cellulitis, 1 pharyngitis, 1 systemic CMV and 1 clostridium difficile infection (CDI) vs 7 (8.2%) in the non-anti-TNF group (2 intra-abdominal abscess, 1 herpes zoster infection, 1 CDI, 1 cellulitis and 2 bronchitis, p=1). Hospitalization and surgery rates were 25.8% and 12.9% in anti-TNF vs 22.9% and 8.4% in non-anti-TNF groups respectively, (p=NS) [Table 2]. In a multivariate logistic regression analysis adjusted to type of FLBT, age, gender, CCI, dose escalation, and treatment with CS and IMM, no variable was significantly associated with the development of AEs (p=NS). Conclusion Anti-TNFs and vedolizumab/ustekinumab have similar safety and drug persistence as FLBT among elderly patients with CD. Larger prospective studies are needed to fortify our findings.

P0595 Comparative effectiveness between ustekinumab and vedolizumab after anti-TNF failure in Ulcerative Colitis: Real-world experience

Abstract Background Ustekinumab (UST) and vedolizumab (VED) have proven to be effective therapies for ulcerative colitis (UC), with similar safety profiles. There are limited real-world studies comparing the effectiveness between UST and VED in UC, especially after anti-TNF failure1–4. Our aim was to evaluate the real-world efficacy and safety of UST and VED in UC patients previously exposed to anti-TNF therapies across multiple Canadian institutions. Methods This was a multicentre retrospective study looking at 12 months of clinical data for patients with UC who had previously been exposed to at least one anti-TNF. These patients were from McGill University Health Centre, Hamilton Health Sciences, and London Health Sciences Centre. The primary outcome was clinical remission at 6 months, defined by a partial Mayo score (pMS) ≤ 2, Mayo Endoscopic Score (MES) ≤ 1, or physician’s judgement of clinical remission. Secondary outcomes included clinical remission at 12 months, clinical response, biochemical remission and response, and drug persistence at 12 months. Clinical response was defined as a decrease in pMS ≥ 2 points or physician’s judgement of clinical response. Biochemical remission was defined as c-reactive protein (CRP) < 5mg/L and/or fecal calprotectin (FCP) < 250μg/g. Biochemical response was defined as a reduction of CRP or FCP by 50% from baseline. These parameters were all evaluated at 6 and 12 months. Adverse events were summarized for all patients after 12 months. Results One hundred and fifty patients were included: 28 in UST and 122 in VED. Mean age was 38.4 (SD 15.6) in UST and 43.8 (SD 16.8) in VED. Percentage of female patients was 67.9% in UST and 53.3% in VED. Mean baseline partial mayo score was 3.78 (SD 3.07) for UST and 4.48 (SD 2.43) for VED. Mean disease duration was 10.63 years (SD 8.44) for UST and 11.80 years (SD 8.25) for VED. There was no significant difference in clinical remission between UST or VED, for data that was available at each time point (UST 65.0% vs. VED 72.6%, p=0.49 at 6 months; UST 68.4% vs. VED 82.3%, p=0.17 at 12 months). There was no significant difference between UST and VED for biochemical remission at 6 and 12 months. Higher MES at baseline was negatively associated with clinical remission in UST and VED with univariate analysis, though only significant in VED when adjusted for sex, age, and disease duration (OR 0.07, 95% CI [0-0.26], p=0.0006). There was no significant difference between drug persistence at 12 months (95.0% UST vs. 91.5% VED, p=0.41). Infectious adverse events were similar between groups (17.9% UST vs. 4.1% VED, p=0.07), with no serious adverse events. Conclusion This real-world multicentre Canadian study shows similar efficacy and safety profiles for UST and VED in UC over 1 year.

P0708 Advanced Therapies in Elderly Patients with Inflammatory Bowel Disease: A Comparative Retrospective Cohort Study in Taiwan

Abstract Background Inflammatory bowel disease (IBD) primarily affects young people, but increasing evidence indicates a shift toward older age. Elderly-onset IBD has several unique features, including atypical presentations and a higher risk for infections and malignancies. However, no studies have compared the clinical outcomes and analyzed the persistence of different advanced therapies in elderly-onset IBD patients. This study aims to address this gap. Methods In this retrospective cohort study, we included all IBD patients receiving advanced therapies and regular follow-ups at the Chang Gung IBD Center from October 2017 and September 2023. Patients were divided into two groups: the elderly-onset group (diagnosed with IBD at age 60 or older) and the control group (diagnosed with IBD before age 60). We compared one- year drug persistence, opportunistic infections, IBD-related admissions, complications, surgeries, and the number of acute flare-ups between the two groups. Additionally, we compared the one-year persistence of different advanced therapies within the elderly-onset group. Results We enrolled 511 IBD patients, with 107 in the elderly-onset group and the remaining in the control group. The elderly-onset group had higher body mass index, more cases of ulcerative colitis, fewer smokers, lower white blood cell count, lower hemoglobin, lower albumin, and a lower proportion of Montreal L3, B2, but a higher proportion of Montreal E1 and E3 diseases, and more Vedolizumab users compared to the control group. In terms of clinical outcomes, both groups had similar steroid-free remission rates, one-year persistence of advanced therapies, opportunistic infections, IBD-related complications, surgeries, and flare-ups. In the elderly group, Infliximab and Ustekinumab showed higher one-year persistence in Crohn’s disease (CD), but there was no statistically significant difference in ulcerative colitis (UC) according to the Kaplan-Meier analysis. There were three independent predictors for one-year advanced therapies persistence, included Montreal L1 (OR:6.722; 95% CI: 1.296-34.852; P=0.023) , Ustekinumab user (OR: 5.672; 95% CI: 1.138-28.267; P=0.034) and hemoglobin (OR: 1.612; 95% CI: 1.210-2.147; P=0.001) with an optimal cutoff value of 11.65 g/dL. Conclusion Elderly-onset IBD patients have unique clinical characteristics. Different advanced therapies persist in elderly-onset CD, but not in UC.

P0772 Efficacy and consumption of golimumab is similar with European and American dosing regimens in Ulcerative Colitis: Results of a prospective study

Abstract Background Golimumab is a subcutaneous TNF-alpha inhibitor approved for ulcerative colitis in European Union (EU) and United States of America (US). Interestingly, maintenance dose for patients weighing ≤80 kg is different in EU and US. In EU, golimumab maintenance dose in 50 mg every 4 weeks with an option of reactive dose escalation to 100 mg every 4 weeks in case of inappropriate response. In US, maintenance dose is 100 mg every 4 weeks for all patients, irrespective of body weight and response to induction. Here we compared efficacy, safety and drug consumption of EU and US maintenance dosing of golimumab in patients weighing ≤80 kg. Methods In this investigator initiated prospective study (ClinicalTrials.gov ID: NCT04156984) we recruited 29 patients with active ulcerative colitis. After common induction (golimumab 200 mg at baseline and 100 mg at week 2) all patients received 1 year of maintenance treatment. First 15 patients received US maintenance regimen with 100 mg golimumab monthly and next 14 patients received EU maintenance regimen with 50 mg golimumab monthly. Those in EU regimen with inadequate response to induction or loss of response during maintenance phase (rectal bleeding score (RBS) > 0 or endoscopic Mayo score (eMayo) ≥ 2) increased dose of golimumab from 50 mg to 100 mg. Co-primary endpoints were endoscopic improvement (eMayo ≤ 1) at weeks 14 and 50 and clinical remission (RBS = 0 and stool frequency score (SFS) < 2) at weeks 14, 26, 38, and 50. Statistical analysis included Chi-square and Mann-Whitney tests. Results Patient demographic data are shown in Table 1. Endoscopic improvement and clinical remission rates were similar with EU and US maintenance regimens (Figure 1). 8/14 (57%) of patients in EU regimen needed dose escalation to 100 mg due to inadequate response after a median of 8.6 weeks (interquartile range 6 to 14 weeks). Drug persistence and drug consumption was similar in both maintenance regimens (Figure 1). In the US regimen 3 potentially drug-related side effects occurred (one case each: one-dermatome herpes zoster, labial herpes, skin small vessel vasculitis), but none in the EU regimen. Conclusion In this prospective study, EU and US golimumab maintenance regimens resulted in similar endoscopic improvement and clinical remission rates during the first year of treatment with golimumab in patients with ulcerative colitis weighing ≤80 kg. Due to high dose escalation rates in EU regimen dose consumption was similar in both maintenance regimens.

P0602 Long-term effectiveness and safety of ustekinumab dose escalation in patients with refractory ulcerative colitis: a multicenter retrospective cohort study

Abstract Background Ustekinumab dose escalation (DE) may be an effective strategy to recapture clinical response in patients with ulcerative colitis (UC). The aim of this study was to assess the real-world long-term effectiveness and safety of ustekinumab DE in patients with refractory UC. Methods This multicenter retrospective cohort study included patients with refractory UC who received at least one IV induction ustekinumab dose between January 2016 and November 2021. We compared ustekinumab DE to no DE, examining clinical, biochemical, and endoscopic disease outcomes. The primary endpoint was corticosteroid-free clinical remission (partial Mayo score ≤ 2 without systemic corticosteroids) at the end of follow-up. Cox-proportional hazards regression analysis was performed for factors associated with time to DE, and a Kaplan-Meier plot was created for visualizing drug persistence probabilities. Results We enrolled 121 patients. Eighty-one patients (67%) underwent DE during a median follow-up of 141 weeks. Corticosteroid-free clinical remission at the end of follow-up was achieved for 53.2% (DE group) and 59.0% (non-DE group). In the DE group, 53% discontinued ustekinumab, mainly due to a lack of effectiveness. At the end of follow-up, 47% of DE patients remained on ustekinumab, compared to 55% in the non-DE group. Ustekinumab persistence probability after 2 years was 40% (DE group) versus 79% (non-DE group). Only 2 patients discontinued ustekinumab for adverse events. Conclusion Our results indicate that DE is a common method for optimizing ustekinumab treatment in refractory UC. While DE appears safe, effectiveness and drug persistence of DE beyond 2 years are limited.

P0631 Short-term effectiveness of risankizumab in patients with Crohn´s Disease: Experience in our centre

Abstract Background The recent introduction of Risankizumab to the therapeutic arsenal for Crohn’s disease (CD) has represented a revolution, owing to the positive efficacy outcomes observed in pivotal studies. Our aim was to assess the short-term effectiveness and safety of Risankizumab in CD patients in routine clinical practice. Methods A retrospective, observational, single-centre study was conducted, including CD patients undergoing treatment with Risankizumab who had completed at least the induction phase (week 12). The primary endpoint was clinical remission, defined as a Harvey-Bradshaw Index (HBI) ≤ 4. We analysed baseline and end-of-follow-up (weeks 12-24) results for clinical remission, faecal calprotectin (FC), and C-reactive protein (CRP). Additionally, drug persistence at the end of follow-up was also analysed and adverse events were recorded. Results A total of 36 patients were included, with a median age of 45 years [IQR 34-54] and a median disease duration of 9 years [3-18]. The predominant location and pattern were ileocolonic and inflammatory, respectively. The 77.8% (28/36) had failed two or more biologics, and 3 patients were biologic-naïve (Table 1). The median baseline HBI was 8 [IQR 6-8], decreasing to 4 [IQR 2-5] at the end of follow-up between weeks 12-24 (p <0.001) (Figure 1A). The median baseline FC was 880 μg/g [IQR 640-2200], decreasing to 400 μg/g [220-575] at the last evaluation, between weeks 12-24 (p <0.001) (Figure 1B). Regarding CRP, the median baseline was 5 mg/L [IQR 2-7], decreasing to 2 mg/L [IQR 2-5] at the end of follow-up (p= 0.003) (Figure 1C). Up to 94.4% of patients maintained Risankizumab at the end of follow-up (Figure 1D). Adverse events (AEs) were observed in 4 patients, of whom 2 had to discontinue treatment without being able to attribute the experienced AEs to the drug. Conclusion In our cohort of CD patients treated with Risankizumab, 64% achieved clinical remission in the short term, maintaining treatment at the end of follow-up in 94%. Our results are comparable to those obtained in the drug’s clinical trials.

P1177 Factors Driving Persistence to First-Line Advanced Therapies in Inflammatory Bowel Disease – A Real-World Study

Abstract Background Advanced therapies, including biologics and small oral molecules, are the mainstay of inflammatory bowel disease (IBD) management. Nonetheless, factors driving drug persistence - defined as the duration from initiation to discontinuation of a therapy- remain unclear. This study aimed to evaluate the persistence of first-line advanced therapies in a real-word IBD cohort and identify factors influencing it. Methods Demographic and clinical data from IBD patients who initiated first-line advanced therapies after 2010 at the San Matteo Hospital Foundation were retrospectively collected in September 2024. Persistence and discontinuation, due to failure or other reasons, were recorded. Differences in persistence probability between therapies were analysed using the log-rank test. Univariate (Fisher’s exact test for categorical variables and t-test or Mann-Whitney for continuous variables) and multivariate (logistic regression) analyses were conducted to assess factors influencing persistence versus discontinuation due to failure. Results Among the 274 recruited patients (median age 42.5 years; F/M 119/155; 146 with Crohn’s disease (CD) and 128 with ulcerative colitis), 159 (58%) started infliximab, 76 (28%) adalimumab, 26 (9.5%) vedolizumab, 3 (1%) ustekinumab, 3 (1%) Janus-kinase inhibitors and 7 (2.5%) other advanced therapies as first-line treatment. Persistence was observed in 141 patients (51.5%), while 70 (26%) discontinued due to failure, 19 (6.9%) due to allergy/intolerance, 18 (6.6%) due to remission, 2 (0.7%) due to immunogenicity, and 24 (8.8%) for other/unknown reasons. No significant difference in drug persistence was observed between therapies (p=0.11). Univariate analysis identified CD phenotype (p<0.01), disease duration (p=0.01), concomitant mesalamine (p<0.01) or steroids (p<0.01), and therapy optimisation (p<0.01) as factors influencing persistence. A trend toward higher faecal calprotectin levels was observed in the discontinuation group (550 vs 385 mg/kg, p=0.09), while subcutaneous administration showed a slightly higher persistence rate (45% vs 33%, p=0.11). Multivariate analysis confirmed the CD phenotype as factor associated with higher persistence, while therapy optimisation was identified as a risk factor for discontinuation. Conclusion While persistence rates were similar across therapies, multiple factors influence persistence or discontinuation, offering potential guidance for optimising IBD management.

P1306 Impact of HLA-DQA1*05 genotype in immunogenicity and response to treatment with Tumour Necrosis Factor-alpha Antagonists in Inflammatory Bowel Disease patients

Abstract Background Carrying the HLA-DQA1*05 gene has been linked to a higher risk of developing immunogenicity in patients with inflammatory bowel disease (IBD) who are treated with tumor necrosis factor-alpha (TNF-a) inhibitors. However, studies have shown inconsistent evidence regarding its connection to a loss of response or adverse events in patients with IBD. The aim is to determine the impact of carriage of HLA-DQA1*05 allele on effectiveness, drug persistence and safety in patients diagnosed with IBD who had received antiTNF-a inhibitors. Methods Retrospective, single-center cohort study including IBD patients who had received anti-TNF therapy. The HLA-DQA1*05 allele was determined retrospectively from a saliva sample (kit OGD-600 de DNA Genotek Oragene) and DNA extraction with the Maxwell® RSC-Stabilized Saliva DNA kits. We evaluate drug persistence, withdrawal of antiTNF-a, clinical response/remission, primary and secondary loss of response, through antiTNF levels, development of antiTNF antibodies and adverse events in patients distributed by HLA-DQA1*05 allele presence. Results A total of 82 patients were included. Baseline characteristics are detailed in Table 1. HLA-DQA1*05 was positive in 35/82 (42.7%) patients. Sixty-three patients (63%) received infliximab (IFX) and 19/82(23.2%) adalimumab. AntiTNF was the first advanced therapy in 78/82(95%) of the cohort. Thirty-four out of 82 patients (41%) received an optimized antiTFN-a regimen, as well as 34/82 (41%) were treated with combo-therapy with immunosuppressants. AntiTNF-a was withdrawn in 35/82 (42.7%) patients during follow-up, and the rate of adverse events that led to discontinuation of the drug was 16% (13/82). When we compared the rate of primary and secondary non-response, persistence of the antiTNF-a therapy or use of combo-therapy, we did not find significant differences between patients by HLA-DQA1*05 status. On the other hand, the rate of infusion reactions, development of anti-TNF antibodies or adverse events that led to drug withdrawal were also similar among patients HLA-DQA1*05 positive or negative. Only the need of optimized antiTNF-a was more frequent among patients HLA-DQA1*05 positive (19(54.3%) vs. 15 (31.9%), p= 0.028). Conclusion In our real-life cohort of IBD patients treated with antiTNF-a, being an HLA-DQA1*05 carrier did not act as a predictor of loss of response, either primary or secondary. The safety of anti-TNF treatment has also not been influenced by the variant. However patients HLA-DQA1*05 positive required optimized antiTNF-a regimen more frequently.

P1115 Short- and Mid-term Effectiveness and Safety of Risankizumab in Refractory Crohn’s Disease: A Retrospective Study

Abstract Background Risankizumab (RSK) is the first anti-IL-23 drug approved in 2022 for moderate-to-severe Crohn’s disease (CD). Data on its real-world effectiveness and safety remain limited. This study assesses the short- and mid-term effectiveness of RSK and its safety profile in a clinical practice setting. Methods A retrospective analysis was conducted on patients with refractory luminal CD treated with RSK at our tertiary centre between March 2022 and July 2024 who completed induction therapy. The primary endpoint was clinical remission at weeks 12 and 24, assessed via the Physician Global Assessment (PGA) based on symptoms, laboratory data and endoscopy/imaging if available. Secondary endpoints included at least clinical response, steroid-free remission and response, adverse events, and drug persistence. Results Sixty-three patients were included (65% male, median age 31 years, median disease duration 9.8 years), with 95.2% previously exposed to anti-TNF, 82.5% to ustekinumab, and 52.4% to vedolizumab; 60% had prior exposure to three biologics, 25.4% to four, and 44% had undergone intestinal resection. Induction (600 mg) was administered intravenously in 88.9% of cases. At week 12, remission and at least partial response rates were 25.4 % and 76.2%, respectively, while steroid-free remission and response rates were 22% and 65.1%. By week 24, 35 patients remained in the study, achieving remission/response rates of 25.7% and 62.8%, respectively, and steroid-free rates of 18.2% and 48.5%. No significant differences were found regarding prior ustekinumab exposure or response/remission outcomes between weeks 12 and 24. RSK persistence was 93%, with four patients discontinuing due to nonresponse. Additionally, by week 24, four patients had required reinduction with 1200 mg administered intravenously. Three adverse events (headache, insomnia, arthralgia) were mild and did not require treatment discontinuation. Conclusion Risankizumab demonstrated encouraging effectiveness in treating refractory Crohn’s disease, achieving clinical responses and steroid-free remission in the short- to mid-term. High drug persistence and a favorable safety profile highlight its potential as a valuable treatment option in real-world settings.

P1070 Comaparison of Effectiveness and Perisitence Anti-TNF drugs on Perianal Fistulizing Crohn’s Disease: A Single Tertiary IBD Referral Center Experience

Abstract Background Perianal Crohn’s disease (CD) is a debilitating and often challenging manifestation of Crohn’s disease that involves the formation of fistulas, abscesses, and other inflammatory lesions around the anus and perineal area. It is associated with significant morbidity, including pain, recurrent infections, and impairment of daily activities. Treatment of perianal CD is complex, requiring a multidisciplinary approach to control disease activity, promote healing, and preserve anal function. Anti-TNF (tumor necrosis factor) biologic agents, such as infliximab and adalimumab, have become a mainstay in the management of perianal Crohn’s disease. However, there is still a debate which anti-TNF agents acts better than other in this subset of patients. Here in this study, we aimed to evaluate the compare the efficacy and persistence of two Anti-TNF agents in perianal Crohn’s disease. Methods This was a single center, retrospective cohort analysis of patients with Crohn’s disease either received adalimumab or infliximab as a first line biologic treatment. A total of 396 patients were included to this analysis. Demographic information such as gender, age, Montreal classification, smoking and prior medications were noted from patients electronic medical records. Weighted Kaplan-Meier and Cox models were used to assess the outcomes. Results Out of 446 Crohn’s disease patients, 128 patients had perianal Crohn’s disease. Gender, smoking, extraintestinal manifestations presence and family history were not different between patients with and without perianal disease. However, in perianal disease group there was more concomitant immunomodulator use than in patients with no perianal involvement (61.5% vs 49.4%, p<0.05). Anti-TNF drug persistence was significantly higher in patients without perianal involvement when compared to patients with with perianal involvement (Figure 1). There was no significant difference in drug persistence rates in perianal Crohn’s disease between infliximab and adalimumab treatment (Figure 2). The concomitant use of immunomodulator drugs did not make any impact. Conclusion In Crohn’s disease patients, anti-TNF medication persistence rates was observed to be significantly lower in those with perianal involvement. However, which anti-TNF agent was chosen as first line biologic did not change medication persistence rates. Concomitant thiopurine use did not make any impact on the results.

P0709 Patient Satisfaction with Subcutaneous versus Intravenous Vedolizumab: A Prospective Observational Study

Abstract Background Vedolizumab (VDZ) is a selective biologic agent that is available in both intravenous (IV) and subcutaneous (SC) forms for maintenance treatment. The SC route offers advantages such as the convenience of self-administration, although some patients may prefer the IV route. The aim of our study was to determine patients’ preferences and satisfaction with their treatment when switching to VDZ SC or continuing with an IV administration. Methods A prospective, observational study was conducted in patients with inflammatory bowel disease (IBD) receiving VDZ IV who were in clinical remission. Patients had the option to continue with VDZ IV or switch to SC and were grouped according to their preference. A baseline visit (before the switch) and another at 24 weeks were conducted. During both visits, patients completed the treatment satisfaction questionnaire (SATMED-Q) and quality of life questionnaire (IBDQ9). Clinical activity, treatment adherence, adverse effects, general bloodwork, and fecal calprotectin were also analyzed. Results Forty-one IBD patients were included, 43% of which were women, and 63% had ulcerative colitis. Almost half (41%) continued with VDZ IV while 59% switched to SC. There were no differences in gender, type, or characteristics of IBD between the groups. However, the age of patients in the SC group was significantly younger than that of the IV group (median 46 [32-63] vs. 66 [59-77] p=0.03). Fewer patients in the SC group had previously received IV biologics (SC 31% vs. IV 69%, p=0.012). The median SATMED-Q before the switch was lower in the SC group (SC 53 [40-61] vs. IV 61 [46-64], p=0.032), as was the IBDQ9 (SC 65.5 [59.4-68.5] vs. IV 70.8 [68.5-77.1], p=0.037). At 24 weeks, there were no differences in SATMED-Q or IBDQ9 scores or disease clinical activity. Drug persistence and frequency of adverse events were similar in both groups. Vedolizumab levels increased significantly in the SC group at 24 weeks (p=0.041). Conclusion Switching to VDZ SC showed similar treatment satisfaction to VDZ IV at 24 weeks in IBD patients, with comparable clinical outcomes and safety profiles. There was a clear preference for subcutaneous administration among younger patients and those without previous IV treatment. This suggests that patient demographics and prior treatment experiences can influence the choice of administration route. The lack of significant differences in clinical outcomes, quality of life scores, and treatment satisfaction between the SC and IV groups at 24 weeks highlights the clinical equivalence of these two administration routes for maintenance therapy in IBD.

P0711 The Effect of Extraintestinal Manifestations Presence on Treatment Persistence in IBD Treatment

Abstract Background Inflammatory Bowel Disease (IBD), which includes Crohn’s disease and ulcerative colitis, is a chronic, relapsing inflammatory disorder of the gastrointestinal tract. A significant portion of patients also experience extra-intestinal manifestations (EIMs) that involve various organ systems beyond the intestines. EIMs are often present at the onset of disease or may develop later during the course of IBD, and their severity can vary, influencing overall disease prognosis and quality of life. Effective management of IBD requires a holistic approach that not only addresses the intestinal inflammation but also anticipates and treats these extra-intestinal complications. In this study we aimed to investigate the role of EIM presence on anti-TNF treatment persistence in IBD therapy. Methods This was a single center, retrospective cohort analysis of patients with IBD either received adalimumab or infliximab as a first line biologic treatment. A total of 673 patients were included to this analysis. Demographic information such as gender, age, Montreal classification, EIM presence, smoking and prior medications were noted from patients electronic medical records. Weighted Kaplan-Meier and Cox models were used to assess the outcomes. Results Out of 673 patients, 426 patients had Crohn’s disease, 240 patients had ulcerative colitis and 7 patients had indeterminate colitis. Overall, 379 pateints received adalimumab and 294 patients received infliximab as first line biologic treatment for IBD. While 272 patients had EIM, 349 patients did not have EIM accompanying their IBD. EIM presence was not concluded in 52 patients from their medical charts. Smoking and family history were not different between patiemnts with and without EIM. However, female patients had statistically more EIM (51.3% vs. 38.1%, p<0.05) and patients with Crohn’s disease had statistically more EIM (49.4% vs 34.5%, p<0.05). Anti-TNF drug persistence was significantly higher in patients with EIM when compared to patients with no EIM (Figure 1). This difference was independent of the type of anti-TNF medication used. However, in patients with ulcerative colitis the difference became more significant, while in Crohn’s disease patients although there is trend, the difference was not significant. The concomitant use of immunomodulator drugs did not make any impact. Conclusion In IBD patients, anti-TNF medication persistence was observed to be significantly longer in those with EIM. This difference was significantly greater in ulcerative colitis patients compared to Crohn’s patients. This difference was independent of the concomitant medication use.

P1130 Real-life histological remission in Ulcerative Colitis patients treated with Ustekinumab: results from the Belgian SULTAN trial

Abstract Background Histological remission is an aspirational therapeutic target in Ulcerative Colitis (UC) associated with lower relapse rates.1Ustekinumab (UST), a monoclonal antibody against the p40 subunit of interleukin (IL) 12 and 23 has shown in the UNIFI trials to be effective and safe in patients with moderate-to-severe UC. However, real-life data on histological remission rates are sparse. The aim of the study was to assess the real-life histological response and remission rates of UST in patients with UC across Belgian hospitals. Methods In this multicentric, retrospective observational study, patients with UC who initialised UST treatment between September 2020 and July 2023 were included. Histological remission was defined as Nancy score = 0, response as Nancy ≤ 1 and assessed at week 16 and 52 by the local pathologist. Other endpoints included steroid-free clinical remission (partial Mayo ≤ 2 with no subscore >1), endoscopic remission (endoscopic Mayo = 0), endoscopic response (Mayo score ≤ 1) and clinical response (decrease in partial Mayo score ≥ 3 points and ≥ 30% plus a decrease in rectal bleeding score ≥ 1 or an absolute rectal bleeding score ≤ 1). UST drug persistence was analyzed by Cox regression analysis, predictors of other endpoints by logistic regression. Results 120 patients with moderate to severe UC (86% patients with ≥S2 severity) were included across 16 participating centers. Median disease duration was 11 years (IQR 9) and 81 (68%) of patients had previously failed 2 or more biologicals. Histological remission was achieved in 3/37 (8%) and 5/45 (11%) at W16 and W52, while histological response was seen in 10.8% (4/37) and 26.7% (12/45) respectively. Steroid-free clinical remission rates were 41/120 (34%) and 38/85 (44%) while endoscopic remission was seen in 23/120 (19%) and 13/52 (25%) at W16 and 52 respectively. Two patients (40%) in histological remission at W52 had an endoscopic Mayo 0 score, while 3 had a Mayo 1 (60%) at the time of evaluation. Active smoking was a negative predictor for achieving steroid-free remission (OR 0.412, p=0.011). No significant predictors for histological remission or response could be identified. UST drug persistence by week 52 was 70.8%. Active smoking (OR 3.058, p=0.02), vedolizumab non-response (OR 2.592, p=0.03) and a high Nancy baseline score (OR 2.46, p=0.04)) were associated with UST failure Conclusion In this multi-centric, real-life cohort with highly refractory UC patients, UST shows acceptable clinical and endoscopic remission rates, but histological remission rates remain low after one year of treatment.

P0826 Switching to standard-dose subcutaneous vedolizumab increases the percentage of patients in biochemical remission even in those intensified with intravenous vedolizumab: one year results of a Spanish multicentre observational study

Abstract Background Analyse the percentage of subcutaneous drug persistence and pharmacokinetics in patients undergoing intravenous (iv) vedolizumab after switching to Subcutaneous (sc) vedolizumab. In addition, the relationship between treatment with intensified iv vedolizumab versus patients without intensification. Methods A multicentre, descriptive, observational, and retrospective study of a cohort of 54 patients diagnosed with Ulcerative Colitis (UC) and Crohn´s disease (CD) treated with iv vedolizumab, who underwent a switch to sc vedolizumab. Analyse clinical, biochemical, and analytical parameters; vedolizumab levels during follow-up and need for intensified intravenous treatment in patients on iv vedolizumab treatment and subsequent switch to sc vedolizumab with follow-up during weeks 4, 12, 24, and 52. Results 32 patients (59%) had a diagnosis compatible with UC and 22 patients (41%) with CD. Biochemical remission was achieved in 32 patients (86%). All patients achieved clinical remission. In addition, a progressive increase in vedolizumab levels was evident after switching to sc vedolizumab with statistical significance (p<0.05) during follow-up. Up to 14 patients (25.9%) were on an intensified regimen before switching to sc vedolizumab. All patients were maintained on sc vedolizumab at a dose of 108mg/2 weeks without requiring intensification at medical criteria during the one-year follow-up. Conclusion Up to 20% more patients, after switching from iv to sc vedolizumab, achieved biochemical remission, which was higher in the intensified group (34%), after one year of follow-up with a standard dose of sc vedolizumab.

P0830 Use of FK-adalimumab biosimilar (MSB 11022) in context of biologic switch in Inflammatory Bowel Diseases : 6 months data of the real-world IDEA study

Abstract Background Biosimilars offer similar efficacy and safety when compared to their originators, thereby enhancing patient access to more affordable treatments. FK-adalimumab (FK-ada) is an adalimumab biosimilar approved for the treatment of Crohn’s disease (CD) and ulcerative colitis (UC). FK-ada development included 1,234 subjects treated up to 52 weeks (total 420 patients-year). Since first approval, there have been no unexpected safety signals despite more than 115,000 patient-years of exposure. IDEA is an ongoing real-world study aimed to assess persistence with FK-ada and develop a predictive model of persistence at 12 months. In this study, adult patients with IBD who switched from adalimumab originator or another adalimumab biosimilar to FK-ada are followed up to one year. Methods Data collected include patient characteristics, reasons for treatment switch, clinical status at each follow-up visit including disease activity scores (Harvey-Bradshaw Index (HBI) and Montreal classification), and faecal calprotectin results. Adult patients with either CD or UC were included, those receiving treatment outside of routine clinical care were excluded. Data are presented using descriptive statistics and a logistic regression model will be employed to identify potential predictive factors at 12 months. We present here the baseline characteristics of IBD patients, and the 6 months intermediate results. Results A total of 136 IBD patients (CD: 112, UC: 24) were recruited across France, Germany and Spain, 57% being males, median age of 43 years and median BMI of 25.2 kg/m2. At the time of switch 97.3% of patients with CD and 87.5% with UC were in clinical remission or had mild to moderate disease activity. 54.4% of patients switched to FK-ada from originator, and 45.6% from another biosimilar, with most switches occurring for administrative reasons. A total of 103 IBD patients (CD: 87, UC: 16) completed the 6 months visit. Patients and disease status are summarized in Table 1. The persistence rate of FK-ada at 6 months was 76.4% (CD: 79%, UC: 65.2%). Most permanent treatment discontinuations occurred around 3 months after switch (median 3.6 months), primarily due to adverse events. Since the start of the study 46 patients (34%) experienced at least one adverse event (AE); 16 (12%) had at least one moderate to severe AE and 30 (22%) had AE(s) attributable to FK-ada. Conclusion 6 months after the switch, FK-ada persistence rate was 76,4%. The majority of patients were still in remission or experiencing mild to moderate disease activity. Treatment and tolerance data from the study completion (52-week) will be critical for identifying predictive factors influencing drug persistence after the switch.

P0760 Long-term Efficacy and Persistence of Subcutaneous Infliximab after Switching from Intravenous Infliximab in patients with Crohn's disease: A Real-World Multicenter Prospective Cohort Study in Korea

Abstract Background Subcutaneous infliximab (IFX-SC) has shown comparable efficacy and safety to IV infliximab (IFX-IV) in Crohn's disease (CD), since its launch in 2021. We aimed to evaluate the real-world efficacy and durability of IFX-SC within two years of follow-up in a Korean patient cohort. Methods This multicenter, prospective cohort study, conducted from September 2021 to June 2024, included patients with CD receiving IFX maintenance therapy. Patients received IFX-SC 120 mg at 8 weeks after the last IFX-IV administration (Week [W] 0), and every 2 weeks thereafter. Clinical relapse (CREL) at W26, W50, W74, and W98 and drug survival within W98 were assessed. Among CD patients with W0 clinical remission, CREL was defined as Crohn’s disease activity index ≥150 points. Drug survival was evaluated based on the time of drug persistence from W0 to the last date of IFX-SC administration among drug-off cases. Results A total of 372 patients with CD were finally included. Enrolled patients included young adults with a male predominance (Table 1). Most of the patients had ileocolonic disease, and about half had non-stricturing/non-penetrating disease phenotype. At W0, 283 patients with CD showed clinical remission., and the proportion of CREL showed incremental trend (W26 CREL 6.8%, W50 CREL 12.2%, W74 CREL 17.7%, and W98 CREL at 25.3%, Ptrend 0.004) (Figure 1A). On the other hands, drug durability was also investigated as shown on Figure 1B. Drug survival rate at W50 and W98 were 93.4% (95% confidence interval [CI], 0.908–0.961) and 91.3% (95% CI, 0.882–0.945), respectively. During the study, drug re-switch rate was 8.6% (32/372), mainly due to injection site discomfort, and also less than 5% of serious adverse events were reported. Conclusion In real-world settings, IFX-SC administration presents a viable strategy for maintenance therapy subsequent to IFX-IV treatment. Given the favorable drug durability, low relapse rate, and tolerable safety profile, IFX-SC may facilitate more tailored and individualized therapeutic approaches.

P0809 Higher Ustekinumab Concentrations in Induction are associated With Better Endoscopic Outcomes in Inflammatory Bowel Disease

Abstract Background Ustekinumab (UST) is a monoclonal antibody targeting the p40 subunit of interleukin-12/23. Evidence suggests a relationship between UST concentrations and therapeutic outcomes. This study aimed to evaluate the association between UST trough concentrations during the induction phase and clinical and especially endoscopic outcomes at week 24 in patients with Crohn’s disease (CD) and ulcerative colitis (UC). Methods Patients with CD and UC were included from the start of UST treatment. Intensification and maintenance regimens were based on standard clinical practice. UST trough concentrations were measured at weeks 8,16, and 24 after induction. The primary objective was to assess endoscopic remission at week 24, defined as a simple-endoscopic-score (SES-CD) ≤2 for CD and a Mayo endoscopic score (MES) ≤1 for UC. Secondary endpoints included clinical remission, and endoscopic improvement. Quartile analysis and logistic regression assessed the relationship between UST concentrations and endoscopic outcomes, while logistic and Cox proportional hazards regressions identified variables associated with endoscopic remission and treatment discontinuation, respectively. The diagnostic performance of UST concentrations was assessed with receiver operating characteristic (ROC) curve analysis. Results Seventy patients (45 with CD) were enrolled. Those achieving endoscopic response and remission at week 24 had higher UST levels at week 8 (4.0 μg/mL vs. 2.5 μg/mL, p=0.002; 3.9 μg/mL vs. 2.9 μg/mL, p=0.047). Patients with UST concentrations in the fourth quartile (Q4) at week 8 (> 4.5 μg/mL) had higher rates of endoscopic remission (69% [Q4] vs. 23% [Q1], p=0.014; 24% [Q2], p=0.003; 31% [Q3], p=0.024). A UST concentration threshold of 4.5 μg/mL at week 8 was the best predictor of endoscopic remission (AUC=0.678, sensitivity 52.5%, specificity 84.6%), while 3.5 μg/mL predicted endoscopic response (AUC=0.732, sensitivity 63.6 %, specificity 73.1 %). Logistic regression did not reveal other predictive factors for endoscopic response/remission other than higher through concentrations at week 8. Longer disease duration correlated with a higher risk of UST discontinuation (OR 1.034, 95% CI 1.002-1.068, p=0.035). Fourteen (20%) patients discontinued UST after a median of 15.50 months. Higher UST concentrations in Q4 did not result in greater drug persistence (p=0.319). Conclusion UST concentrations at week 8 were positively associated with endoscopic outcomes at week 24, with a threshold of 4.5 μg/mL reliably predicting endoscopic remission. Further randomized clinical trials are warranted to explore whether optimizing UST treatment based on post-induction concentrations can enhance therapeutic outcomes. References K. Papamichael, E.H. Vogelzang, J. Lambert, G. Wolbink, A.S. Cheifetz, Therapeutic drug monitoring with biologic agents in immune mediated inflammatory diseases, Expert Rev Clin Immunol 15 (2019) 837–848. https://doi.org/10.1080/1744666X.2019.1630273. D. Alsoud, G. De Hertogh, G. Compernolle, S. Tops, J. Sabino, M. Ferrante, D. Thomas, S. Vermeire, B. Verstockt, Real-world Endoscopic and Histological Outcomes Are Correlated with Ustekinumab Exposure in Patients with Ulcerative Colitis, J Crohns Colitis 16 (2022) 1562–1570. https://doi.org/10.1093/ECCO-JCC/JJAC067. C. Mcdonald, H. Kerr, E. Gibbons, T. Lukose, D. Cheriyan, G. Harewood, S. Patchett, A. O’toole, O. Kelly, K. Boland, Higher Ustekinumab Levels in Maintenance Therapy are Associated with Greater Mucosal Healing and Mucosal Response in Crohn’s Disease: An Experience of 2 IBD Centers, Inflamm Bowel Dis 30 (2024) 423–428. https://doi.org/10.1093/ibd/izad073. T. Straatmijer, V.B.C. Biemans, D.J.A.R. Moes, F. Hoentjen, R. ter Heine, P.W.J. Maljaars, R. Theeuwen, M. Pierik, M. Duijvestein, A.E. van der Meulen-de Jong, Ustekinumab Trough Concentrations Are Associated with Biochemical Outcomes in Patients with Crohn’s Disease, Dig Dis Sci 68 (2023) 2647. https://doi.org/10.1007/S10620-023-07822-7.

P0716 Comparison of vedolizumab and ustekinumab treatment persistence in anti-TNF experienced perianal Crohn’s Disease patients: A Single Center Experience

Abstract Background Perianal Crohn’s disease (CD) is a particularly challenging and debilitating complication of Crohn’s disease. This can lead to significant morbidity, including chronic pain, and recurrent infections, all of which severely impact a patient’s quality of life. Biologic therapies, particularly tumor necrosis factor (TNF) inhibitors, such as infliximab and adalimumab, have become central to the management of this condition due to their ability to target key inflammatory pathways driving both intestinal and extra-intestinal disease. In addition to Anti-TNF agents, other biologics such as integrin inhibitors (e.g., vedolizumab) and interleukin inhibitors (e.g., ustekinumab) have shown promise in treating refractory or complex perianal Crohn’s disease. In this study, we aimed to compare the persistence rates of vedolizumab and ustekinumab in anti-TNF experienced perianal Crohn’s disease patients. Methods This was a single center, retrospective cohort analysis of Anti-TNF treatment experienced Crohn’s disease patients either received vedolizumab or ustekinumab as a treatment. A total of 176 patients were included to this analysis. Demographic information such as gender, age, Montreal classification, smoking and prior medications were noted from patients electronic medical records. Weighted Kaplan-Meier and Cox models were used to assess the outcomes. Results Out of 176 Crohn’s disease patients, 128 patients had perianal Crohn’s disease. 41.5% of the patients were female, where as 33.7% of the patients had extraintestinal manifestations and 41.7% of the patients had fistulizing disease. EIM was less frequent in fistulizing disease (26% vs. 39.2%, p<0.05), concomitant azathioprine use was more frquent in fistulizing disease (58.9% vs. 34.3%, p<0.05) and fistulizing disease patients were predominantly male (67.3% vs 32.7%, p<0.05). Use of vedolizumab and ustekinumab did not different in fistulizing disease. In general cohort, the persistence rate was higher in ustekinumab treated group (Figure 1) where as in fistulizing disease group there was no statistically difference in persistence rate between two treatment arm (Figure 2). Conclusion To conclude, there is a shorter drug persistence rate in fistulizing Crohns disease when compared to non-fistulizing Crohn’s disease even with concomitant azathioprine use. While there was a longer drug persistence rate in the ustekinumab arm compared to the vedolizumab arm in the overall group, no significant difference was observed between both treatment arms in the fistulizing subgroup. Figure : 1 Figure 2:

Assessing early therapeutic drug monitoring of adalimumab as a predictor of treatment efficacy and immunogenicity in rheumatic diseases: "early therapeutic drug monitoring of adalimumab".

Therapeutic drug monitoring (TDM) in inflammatory rheumatic diseases (RMDs) is gaining interest. However, there are unresolved questions about the best practices for implementing TDM effectively in clinical settings. The primary objective of this study was to evaluate whether early TDM of adalimumab predicts drug survival at 52 weeks in patients with RMDs. The secondary objective was to identify factors associated with pharmacokinetic failure and treatment discontinuation. A retrospective cohort study included patients aged ≥ 18 years with RMDs who initiated adalimumab therapy. Early TDM was performed within the first 26 weeks, and adalimumab trough levels (ATL) and anti-drug antibodies were measured. Drug survival was assessed at 52 weeks and defined as the time from adalimumab initiation to discontinuation for any reason. Multivariate analyses were conducted to identify factors influencing outcomes. The study included 194 patients, of whom 56.7% exhibited ATL below the therapeutic range during the first 26 weeks. In the multivariate analysis, subtherapeutic concentrations were significantly associated with higher weight (OR = 1.02; p = 0.040) and ankylosing spondylitis diagnosis (OR = 3.68; p < 0.001). At 52 weeks, 43.8% of patients had discontinued adalimumab. Low ATL (< 1 µg/mL) was strongly associated with treatment discontinuation (OR = 7.31; p < 0.001), while concomitant methotrexate reduced this risk (OR = 0.46; p = 0.026). Early TDM of adalimumab predicts drug persistence and underscores its clinical relevance as a proactive tool to guide personalized treatment and reduce the risk of treatment failure. These findings highlight the importance of incorporating TDM into routine practice to optimize therapeutic outcomes. Key Points • Early TDM of adalimumab in rheumatic diseases shows that low drug exposure predicts reduced drug survival at 52 weeks. • Approximately half of the patients exhibit low adalimumab exposure with the standard dose (40 mg every other week). • Body weight and methotrexate use significantly impact adalimumab levels. • Immunogenicity, found in 14.4% of patients with low ADL levels, underscores the need for early ADA detection to prevent non-response and discontinuation.