bluuebunny/crossref_metadata_2025 huggingface dataset:
P688 Patient preferences in medication to treat Ulcerative Colitis: a discrete choice experiment
Authors: Straatmijer T , van den Akker-van Marle E , van der Horst D , Scherpenzeel M , Duijvestein M , van der Meulen A
Published: January 2023

Background

Since the number of treatment options for Ulcerative Colitis (UC) has expanded, patients and physicians face challenges regarding decisions about the medication options. In shared decision making, treating physicians help patients understand the trade-offs and their own preferences. We aimed to identify patients preferences about the relative risks and benefits of UC treatment options in patients with UC in the Netherlands. Furthermore, we assessed after how many failed treatment options, patients are willing to consider surgical treatment.

Methods

We conducted a web-based, discrete choice experiment (DCE) among adult UC patients. Patients were repeatedly asked to choose between two hypothetical treatment options with varying combinations of attribute levels (fig 1). Attributes were based on consecutively a literature search, patient interviews, surveys and a focus group. The six included attributes were: administration route, administration location, chance on symptom reduction (short and long term), chances on infection and on adverse events. A balanced overlap design was used. Patients were recruited via the patient association Crohn & Colitis NL and in two academic hospitals. Data were analyzed by using Hierarchical Bayes estimation.

Results

A total of 172 patients participated in the DCE. Median disease duration was 8 (IQR 3-16) years. Most patients were anti-TNF experienced (52.9%). Symptom reduction after one year (relative importance (RI) 27.7 (95% CI 25.6-29.7)) was the most important when choosing between treatment options (table 1), followed by the chance of infection (22.3 (21.2 - 23.4)) and chance of symptom reduction after eight weeks (RI 19.5 (18.1 - 20.9)). The location of administration of the treatment and the chance of adverse events were the least important (8.7 (7.7 - 9.79) and 8.5 (7.9 - 9.2), respectively). Patients preferred oral administration over subcutaneous injections. Intravenous route of administration was least favorite. The differences in average utilities of patients previous treated with biologic therapy or small molecules or naïve patients are displayed in table 2. 133 patients filled in the trade off questions regarding surgery. Forty-four patients (33.1%) responded with unknown. Nineteen patients (14.3%) would not even consider surgery after failing all treatment options without any new available therapies left. Nine patients would consider surgery before trying any treatment options. Of the remaining patients, nine (6.8%) would consider surgery after failing six treatment options.

Conclusion

We found that symptom reduction after one year was the most important treatment attribute in UC patients. These outcomes can help understand the trade-offs and preferences of UC patients.
P690 Prolonged benefit of filgotinib in patients with Ulcerative Colitis in SELECTION
Authors: Laharie D , Sturm A , Kobayashi T , Matsumoto T , Oortwijn A , Jamoul C , Faes M , de Haas A , Vermeire S
Published: January 2023

Background

Filgotinib (FIL) is a once-daily, oral, Janus kinase 1 preferential inhibitor approved for the treatment of patients with ulcerative colitis (UC) in the UK, EU and Japan. In the phase 2b/3 SELECTION trial (NCT02914522),1 FIL 200 mg (FIL200) was well tolerated and effective in inducing and maintaining clinical remission vs placebo (PBO) in patients with UC. This post hoc analysis of SELECTION data further evaluated the prolonged benefit of FIL treatment from week 10 (W10) until W58.

Methods

In SELECTION, adults with moderately to severely active UC were randomized 2:2:1 to receive FIL200, FIL 100 mg (FIL100) or PBO once daily for 11 weeks in Induction (IND) Studies A and B (biologic-naïve and -experienced patients, respectively). Patients in clinical remission or with a Mayo Clinic Score (MCS) response at W10 (responders) were rerandomized 2:1 to continue their IND FIL dose in the 47-week Maintenance (MNT) Study. This post hoc analysis evaluated the hazard ratio (HR) for protocol-specified disease worsening (PSDW) in patients who continued FIL200 during MNT (FIL200→FIL200) vs those rerandomized from FIL200 to PBO (FIL200→PBO). The proportion of patients with a prolonged benefit at W58 was also evaluated across all FIL200 and FIL100 MNT arms. A prolonged benefit was defined as clinical remission or an MCS response at W58, among W10 responders. Among patients with prolonged benefit at W58, the proportion of those who had Inflammatory Bowel Disease Questionnaire (IBDQ)-remission at W58 was also assessed across all FIL200 and FIL100 MNT arms.

Results

Baseline characteristics were similar between MNT arms, although biologic-experienced status was more common in patients who did not have a prolonged benefit vs those who did. FIL200→FIL200 treatment (n=199) reduced the risk of PSDW by 74% vs FIL200→PBO (n=98) (HR [95% CI]: 0.26 [0.17–0.40]; p<0.0001) (Figure 1). PSDW was the most common reason for discontinuation among patients without prolonged benefit, across all arms. In the FIL200→FIL200 arm, 66.8% of patients who were in clinical remission or had an MCS response at W10 had a prolonged benefit at W58 vs 32.7% in the FIL200→PBO arm. Among patients in clinical remission at W10, 79.3% in the FIL200→FIL200 arm had a prolonged benefit (62.1% clinical remission; 17.2% MCS response) vs 44.4% in the FIL200→PBO arm (30.6% clinical remission; 13.9% MCS response) (Figure 2). In the FIL200→FIL200 arm, 82.0% of patients with prolonged benefit at W58 had IBDQ remission at W58 (Figure 3).

Conclusion

After a year of FIL200 treatment, two-thirds of patients who were in clinical remission or had an MCS response at W10, and ~80% who were in clinical remission at W10, had a prolonged benefit.

1. Feagan BG et al. Lancet 2021;397:2372–84.
P699 Ustekinumab therapy after biologic failure in patients with Crohn’s Disease – A real-world single centre experience
Authors: Majumder S , Bazarova A , Lorenzo Parigi T , Love M , Davis J , Ghosh S , Iacucci M , Shivaji U N
Published: January 2023

Background

Patients with Crohn’s disease (CD) often require multiple biological therapies due to loss of response. Anti-TNF drugs are generally used as first-line biologics followed by a switch of class. Ustekinumab (UST), an IL-12/23p40 antagonist is used often after anti-TNF failure. The aim of the study was to report on the outcomes of UST therapy with a median follow-up period of nearly 24 months.

Methods

All CD patients who commenced UST therapy were identified from EMR at a tertiary referral centre between January 2017 and December 2021. All relevant demographic and clinical data were collected. Data on clinical response (defined as a downgrade in disease activity based on clinician assessment & biochemical parameters), steroid-free duration, and long-term response to UST at 52 and 104 weeks were recorded. The response was assessed clinically and supported by biomarkers, cross-sectional imaging, colonoscopic data, and sustained maintenance of UST. The statistical analysis was carried out using the IBM® SPSS® Statistics software package Version: 28.0.0.0

Results

A total of 147 CD patients (M=65, 44%; median age 38years) were included in the analysis with a median follow-up period of 24 months (range 5-67 months). 82 (56%) patients had stricturing (B2), penetrating (B3) and perianal phenotype at baseline, and 50 (34%) had undergone the previous resection/s. 109 (75%) had documented moderate to severe disease activity and 139 (95%) patients were exposed to at least one biologic prior to treatment with UST. A total of 34 (23%) patients were on concomitant thiopurines at the start of treatment. Among 147 patients in our cohort, 143 (97%) showed clinical response to UST and remained on treatment at the end of the follow-up period. The distribution of patients as per disease activity at baseline, 52 and 104 weeks is illustrated in Figure 1. An improvement in haemoglobin levels was observed post-therapy with UST, which was statistically significant at 104 weeks (p<0.001), with a corresponding significant reduction in faecal calprotectin levels (median reduction from 976 mcg/g ◊ 333 mcg at 104w; p<0.001). Only 13(8.8%) patients had side effects that were directly attributed to UST therapy.

Conclusion

UST is an effective therapeutic option in patients with CD who have failed previous biologic therapy. In our cohort with a large proportion of patients with complicated and refractory disease, clinical response was observed regardless of their previous exposure status to biologics, and disease phenotype. UST appears to be well tolerated with a reasonable safety profile. The consistent response rates even after prolonged treatment periods mean that clinicians could safely continue UST for longer durations, where options are limited.
P708 Post-COVID-19 and Quality of Life in Patients with Immune Mediated Inflammatory Diseases
Authors: Schlosser T , Krasselt M , Elsing L , Hecker M , Holler B , Hoffmeister A
Published: January 2023

Background

Pandemic situation of the novel coronavirus disease (COVID-19) represents a challenging condition with a plethora of aspects. Symptoms of patients with immune mediated inflammatory diseases (IMID) such as inflammatory bowel disease and different rheumatic diseases are not well described. Persistent symptoms following acute COVID-19 are quite frequent.

Methods

IMID patients over the age of 18 years were prospectively asked for participation. Recruitment took place at our university outward centre between April and October 2022. Assessment was conducted as questionnaire-based study about the individual COVID-19 history since start of the pandemic in January 2020.

Results

156 patients filled in the documents. Large part of the participants had a diagnosis of inflammatory bowel disease (117 [75%] vs. 39 [25%] patients with rheumatic disease). Eightyone patients (51%) selfreported about a positive COVID-19 history. Diagnosis had usually been proven by PCR. In general, courses of infection were rather mild: Only two patients (2% of patients with reported COVID-19) were admitted to hospital due to COVID-19 with one of the two in need for intensive care. No symptoms of COVID-19 had been described by seven persons (9% of patients with reported COVID-19). Post-COVID-19 condition represents a not very well described continuum of persisting symptoms following acute course. WHO proposes a definition of at least one symptom, that persists three months from the onset of acute COVID-19. Twenty persons (25%) met this criterion; 19 patients (23%) were still suffering from post-COVID-19 at time of study participation. Quality of life (QOL) was globally assessed by a visual numeric scale (from 0 [=lowest QOL] to 100 [=highest QOL]). Mean/median of QOL reached 71.5/75 points in the cohort without post-COVID- 19 condition compared to 61.9/60 points in the post-COVID-19 cohort, respectively. One-sided t-test showed significant association of post-COVID-19 condition to lower QOL (p=.03).

Conclusion

A notable fraction of IMID patients suffered from post-COVID-19 condition. This condition had negative impact towards quality of life.
P709 Endoscopic healing and clinical remission after administration of adalimumab to patients with Crohn’s disease of the small intestine
Authors: Viazis N , Koustenis K , Veretanos C , Mountaki A , Almpani F , Tsatsa A , Trikola A , Beka H , Arvanitis K , Georgiadi T , Nousias G , Mylonas I , Kozompoli D , Paparizou N , Karaouzas L , Papastergiou V , Archavlis E , Mela M , Christidou A , Varytimiadis K , Hatzievangelinou C , Katopodi K , Vienna E , Mantzaris G
Published: January 2023

Background

In patients with Crohn’s disease (CD) localized in the small intestine, endoscopic healing can be assessed by small bowel capsule endoscopy (SBCE). We aimed to investigate the rate of achieving deep remission, i.e. endoscopic healing and clinical remission in patients with CD of the small intestine, after treatment with adalimumab.

Methods

Retrospective analysis of prospectively collected data from all patients who were subjected to SBCE in our department from 1/3/2003 to 30/9/2022. Out of the patients who were subjected to the test for the investigation of suspected or confirmed CD of the small intestine we sought those who were treated with adalimumab (originator or biosimilar) and underwent repetitive SBCE at least 24 weeks after the start of treatment. Endoscopic healing was defined as a Lewis score < 350, while clinical remission was defined as Harvey Bradshaw index ≤ 4.

Results

During the study period, 102 patients (men/women: 54/48, mean age ± SD: 31.2±14.1 years) were subjected to SBCE before and after administration of adalimumab for the treatment of small intestinal CD. Of these patients, 11 (10.7%) also had extra-intestinal manifestations (arthritis: n=9, erythema nodosum: n=1, uveitis: n=1). After a mean period of 104 weeks (range 24-416 weeks), endoscopic healing was observed in 49 patients (48.0%). All patients who experienced endoscopic healing were also in clinical remission. There was no statistically significant difference in patients with endoscopic healing between those receiving adalimumab originator or biosimilar (36 out of 73, 49.3% vs 13 out of 29, 44.8%, p=NS).

Conclusion

Small bowel capsule endoscopy can help us to identify endoscopic healing, which is observed in about half of patients with CD of the small intestine treated with adalimumab.
P712 Real-World Efficacy And Safety Of Ustekinumab And Adalimumab In Patients With Crohn’s Disease: Propensity Matched Analysis
Authors: Shin Y , Hong S N , Kim E R , Chang D K , Kim Y H
Published: January 2023

Background

Ustekinumab (UST), an anti-IL-12/23 p40 monoclonal antibody, was shown to be as effective and safe as the anti-TNF-alpha monoclonal antibody adalimumab (ADL) in the treatment of Crohn's disease (CD). Most studies on UST in patients with CD have been conducted in the Western patients and lack in Asian patients with CD. This study aimed to compare real-world clinical efficacy and safety of UST with ADL in Korean CD patients with anti-TNF naïve and failure group.

Methods

The retrospective single-center cohort study was conducted on the adult patients with moderated to severe active Crohn’s disease, from 2010 to July 2022. Medical records was extracted from the Clinical Data Werehouse of Samsung Medical Center, Seoul, Korea. Propensity-matched analysis was performed to evaluate patient-reported outcome (PRO)-based clinical remission (PRO3<13) at week 52 and 96 in patient treated with UST and ADL. Subgroup analysis was performed on the biologics-naïve and anti-TNF-failure patients.

Results

A total of 188 CD patients treated with UST and and 299 received with ADL were enrolled. In a propensity -matched cohort adjusted with age, sex, initial CDAI score, and Montreal classification, the clinical remission rate was higher in UST group than ADL at week 52 (Odds ratio [OR] 2.7, 95% confidence interval [CI] 1.31-5.58, P = 0.007) and at week 96 (OR 12.0, 95% CI 1.56-92.29, p = 0.017). In subgroup analysis, there was no significant difference in both group in biologics-naïve group, whereas UST group showed higher clinical remission compared with ADL group in anti-TNF failure group (OR 4.67, 95% CI 1.34-16.23, p = 0.016). Biochemical remission (CRP < 0.05) showed no significant difference between both groups at week 52 and 96. Severe adverse effects leading to biologics discontinuation was numerically high in UST group and ADL group (1, 0.53% vs. 7, 2.34%, p = 0.160).

Conclusion

Compared with ADL, UST showed comparable efficacy in biologic-naïve patients and superior efficacy in anti-TNF failure patients with CD in Korean patients with CD.
P717 Use of tramadol versus traditional opioids and adverse outcomes of Inflammatory Bowel Diseases: a Danish nationwide cohort study
Authors: Dalal R , Lund K , Zegers F , Friedman S , Allegretti J , Norgard B
Published: January 2023

Background

Patients with inflammatory bowel diseases (IBD) commonly suffer from pain that requires analgesic therapies such as tramadol and opioids. However, use of traditional opioids (TOs) has been associated with severe infections and mortality in this population. Tramadol, a partial agonist of opioid receptors, has been considered to have less abuse potential compared to TOs. It is unknown if tramadol is associated with fewer IBD-related complications compared to TOs.

Methods

This was a Danish nationwide cohort study examining adverse outcomes associated with use of tramadol vs TOs in the IBD population. Patients with IBD (ICD-10 codes K50 and K51) diagnosed 1995-2021 in Denmark with subsequent prescriptions for tramadol or TOs were included. For each drug exposure, two populations were defined: initial users (“IUs”; first prescription after IBD diagnosis) and persistent users (“PUs”; first 3 consecutive prescriptions within 365 days after IBD diagnosis). Outcomes included severe (hospital-diagnosed) infection, bowel obstruction or ileus, IBD surgery, and mortality within 90 days after the IU index date (i.e. date of first prescription) and within 365 days after the PU index date (i.e. date of third prescription) (Figure 1). Multivariable logistic regression was performed to determine associations of tramadol vs TOs with outcomes while adjusting for age, sex, Charlson comorbidity index, year of IBD diagnosis, IBD type, IBD duration, and prior immunomodulator use, corticosteroid use, IBD hospitalization, severe infection, bowel obstruction or ileus, and IBD surgery within 6 months before the index date. A sensitivity analysis was performed in which patients with any diagnosis of a malignant neoplasm (ICD-10 codes C00-99) <1 year prior to the first tramadol or TO prescription were excluded.

Results

We identified 37,377 IUs and 15,237 PUs of tramadol or TOs. Baseline characteristics are presented in Table 1. IUs of tramadol had lower odds of severe infection (adjusted odds ratio [aOR] 0.80, 95% CI 0.65-0.99), bowel obstruction or ileus (aOR 0.74, 95% CI 0.53-1.03), and mortality (aOR 0.43, 95% CI 0.35-0.55), and higher odds of IBD surgery (aOR 1.27, 95% CI 1.02-1.60) vs TOs. PUs of tramadol had lower odds of severe infection (aOR 0.69, 95% CI 0.55-0.86), bowel obstruction or ileus (aOR 0.58, 95% CI 0.39-0.85), and mortality (aOR 0.35, 95% CI 0.28-0.44) but no difference in IBD surgery (aOR 1.13, 95% CI 0.86-1.47) vs TOs (Table 2). Results were unchanged after excluding patients with malignancy (Table 3).

Conclusion

Use of tramadol was associated with lower odds of severe infection, bowel obstruction or ileus, and mortality vs use of TOs among patients with IBD. Safety comparisons of tramadol to other analgesics are needed.
P723 Comparison of the Persistence Rates of Biologic Agents in Paediatric Crohn's Disease Patients (Japanese Paediatric IBD Registry Study)
Authors: Nishida D , Ishige T , Arai K , Shimizu H , Iwama I , Nambu R , Kunisaki R , Yaguchi K , Mizuochi T , Murakoshi T , Saito T , Kato S , Kudo T , Iwata N , Inoue M , Yodoshi T , Hagiwara S I , Toita N , Tajiri H , Mochizuki T , Kakuta F , Kumagai H , Noguchi A , Sasaki M , Nishimata S , Aomatsu T , Hirano Y , Shimizu T
Published: January 2023

Background

Biologics are widely used for paediatric Crohn's disease (CD) and are highly effective; however, primary inefficacy and the emergence of secondary inefficacy during long-term use remain challenges. Although it is desirable for biologics used in paediatric patients to be safe and usable long-term, there are few detailed reports on the comparison of persistence rates of biologics in paediatric patients.

Methods

This was a multicentre prospective cohort study using a web-based registry system in Japan that was performed between October 2012 and March 2020. New paediatric inflammatory bowel disease patients diagnosed at less than 18 years of age were enrolled from 23 Japanese hospitals. The persistence rates of the first biologics (Infliximab: IFX and Adalimumab: ADA), and the second biologics (IFX, ADA, and Ustekinumab: UST) were analysed. Patients with unknown outcomes were excluded.

Results

We enrolled 185 patients with CD as the final diagnosis, and 109 (59%) received biologics during the observation period. As the first biologic, IFX was used in 52 (45%) patients, ADA in 52 (45%), UST and Vedolizumab (VED) in one, respectively, and the biologic in one patient was unidentified. The 1-, 3- and 5-year persistence rates of IFX and ADA as the first biologic were 90%, 70% and 61% for IFX, and 80%, 71% and 49% for ADA, respectively (Fig.1), with no statistically significant difference (P=0.31). There was also no statistically significant difference after propensity score matching (P=0.27). Multivariate analysis showed that Paris classification L4a and b were independent risk factors for lower retention of biologics in IFX and ADA. Of the 104 patients whose first biologic was IFX or ADA, 31 patients were treated with a second biologic (IFX: 7, ADA: 6, UST: 15, VED: 2 and unknown: 1). The 1- and 3-year persistence rates of the second biologic were 86% and 51% for IFX; 80% and 80% for ADA and 100% and 100% for UST, respectively (Fig.2).

Conclusion

The persistence rates of IFX and ADA as first biologics were similar in paediatric patients with CD, and the persistence rates of UST tended to be higher than IFX or ADA as second biologics, although the differences were not statistically significant.
P724 Upadacitinib is Effective and Safe in Tofacitinib-Experienced Patients with Ulcerative Colitis: A Prospective Real-World Experience
Authors: Krugliak Cleveland N , Friedberg S , Choi D , Hunold T , Choi N K , Garcia N M , Picker E A , Cohen N A , Cohen R D , Dalal S R , Pekow J , Sakuraba A , Rubin D T
Published: January 2023

Background

The development and availability of Janus kinus inhibitors (JAKinibs) for moderately to severely active ulcerative colitis (UC) provides new therapeutic options with both novel mechanisms and unique pharmacodynamic benefits. Tofacitinib (tofa) is a non-selective pan-JAKinib that received FDA approval for UC in 2018 and upadacitinib (upa) is a JAK-1 selective inhibitor, that received FDA approval for UC in 2022. It is unknown whether patients who do not respond to tofa will subsequently respond to upa. We report our real-world experience with upa in UC patients with primary or secondary non-response to tofa.

Methods

We performed a prospective analysis of clinical outcomes on upa in patients with UC and Crohn’s disease (CD) using pre-determined intervals at weeks 0, 2, 4, and 8 as part of a formalized treatment protocol at our institution. We used the SCCAI and HBI, as well as CRP and fecal calprotectin (FCP) to assess efficacy and recorded treatment-related adverse events and serious adverse events (AEs). Here we report our experience in patients treated with upa who have been previously treated with tofa.

Results

26 patients (18=UC, 8=CD) with primary or secondary non-response to tofa received upa. (Table 1) In addition to tofa, all of these patients failed at least two biologics prior to upa treatment. In UC: by week 2 60% (6/10) achieved clinical response, and 40% (4/10) achieved clinical remission. By week 4 87.5% (7/8) achieved clinical remission, and 87.5% (6/8) achieved steroid-free remission; FCP decreased by a mean of 649.2 μg/g from baseline (+/- 772.7). At week 8: 100% (8/8) of patients achieved clinical response, 87.5% (7/8) achieved clinical remission, and of all of these (7/7) achieved steroid-free remission; FCP decreased by a mean of 180 μg/g (+/- 721.8) from baseline. One patient had follow-up to week 12 and continued to be in steroid-free remission. (Table 2) In CD: by week 2 2 of 2 patients achieved clinical remission, by week 4 3 of 3 were in clinical remission, 2 of 3 achieved steroid-free remission, and one patient had follow-up to week 8 and he remained in steroid-free remission. (Table 2). 6 patients experienced AEs, with the most common being acne (19.2%). No infections, MACE, or VTE occurred.

Conclusion

In this prospective real-world experience in medically-resistant patients with UC and CD who previously failed treatment with tofa and at least two biologics, we describe that upa is rapidly effective, inducing both clinical, steroid-free, and biochemical remission with no serious AEs.
P725 Patients with Immune Mediated Inflammatory Diseases are insufficiently protected against vaccine-preventable influenza and pneumococcal infections due to low vaccination rates
Authors: Van De Pol N , van der Woude C J , Vis M , van Doorn M B A , Derikx L A A P , Molendijk I , de Vries A C
Published: January 2023

Background

Patients with Immune Mediated Inflammatory Diseases (IMIDs) treated with immunosuppressive drugs are at an increased risk of infections and a more complicated course of the infection, including vaccine-preventable infections. National and international guidelines have specified vaccination strategies in patients with IMIDs. However, the adherence to these guidelines in clinical practice is uncertain. Therefore, we evaluated the current vaccination status of patients with IMIDs at the outpatient clinic of the Erasmus MC Rotterdam.

Methods

Between August 2022 and October 2022, a survey was sent out to patients with various IMIDs at the rheumatology, dermatology and gastroenterology outpatient clinics. Only patients on immunosuppressive treatment were included. The survey contained questions on patient demographics, disease characteristics and current vaccination status.

Results

The survey was sent out to 3,345 patients with IMIDs, of whom 1,094 patients filled in the questionnaire (response rate 32.7%). Mean age was 51 ± 16 years and 40.8% were male (Table 1). Patients were treated by a dermatologist (n=306), gastroenterologist (n=414) and/or rheumatologist (n=527). Overall, 55.1% of patients received a yearly influenza vaccination and 9.2% occasionally (Table 2). Furthermore, 8.7% of patients received the pneumococcal vaccination five-yearly and 1.4% occasionally. Both the influenza and pneumococcal vaccination rates were highest in patients with rheumatoid arthritis (64.1%, and 14.7%, respectively). On the contrary, patients with hidradenitis suppurativa had the lowest rates for both the influenza vaccination (32.3%) and pneumococcal vaccination (n=0). Overall, 91.7% of patients (n=1,003) received one or more COVID-19 vaccinations.

Conclusion

Patients with Immune Mediated Inflammatory Diseases are insufficiently protected against vaccine-preventable infections due to low vaccination rates. Better implementation strategies of current guidelines on seasonal influenza vaccination and pneumococcal vaccination are required. A high rate of COVID-19 vaccination was observed, possibly indicating the willingness of patients to receive vaccinations. Further research into facilitators and barriers to vaccination in these specific patient populations is required.
P726 Fecal calprotectin and quality of life questionnaires are responsive to change in pouch disease activity following antibiotic therapy—results from a prospective clinical trial
Authors: Ollech J , Yanai H , Avni Biron I , Dotan I
Published: January 2023

Background

Whether fecal calprotectin (FC) and quality of life (QoL) questionnaires reflect change in disease activity in patients with a J-pouch is unknown.

Methods

Patients with UC following ileal pouch-anal anastomosis developing acute pouchitis were prospectively recruited to a clinical trial at the Rabin Medical Center in Israel, a major referral center for patients with a J-pouch. Consecutive patients with acute pouchitis were diagnosed clinically by the treating physician in a patient with compatible clinical symptoms. Patients were treated with a 2-week course of antibiotics – either metronidazole and ciprofloxacin or metronidazole and doxycycline. Full PDAI, including clinical, endoscopic, and histologic evaluation, was performed at baseline and following 2 weeks of antibiotic therapy. Patients had comprehensive laboratory tests, including fecal calprotectin (FC) measurements at both time points. Patients also filled out QoL questionnaires (short inflammatory bowel disease questionnaire - SIBDQ, inflammatory bowel disease [IBD] disk) at both time points. Outcomes of interest included the responsiveness of FC and QoL questionnaires to change in pouch disease activity according to the PDAI. Paired analyses were performed to compare results between the 2-time points.

Results

Twenty patients were enrolled in a prospective clinical trial. At enrollment, the median age was 36 years IQR [27-56], females 12 (60%). The median interval from the ileostomy closure was 7 years IQR [2-17]. Median PDAI score: 9 IQR [8-11.5], median FC: 661 ug/g IQR [425-1261], median C-reactive protein: 1.1 mg/dl IQR [0.5-1.8] and median hemoglobin: 13.2 g/dl IQR [12.1-14.1].

Following 14 days of antibiotic treatment, there was a significant decrease in the total PDAI, which decreased from a median of 9 IQR[8-11.5] to 6 IQR[2.5-7],(p=0.007). This difference was mainly related to a significant reduction in both the clinical (p=0.01) and endoscopic subscores (p=0.001) but not the histologic subscore (p=0.1). FC was responsive to this change in PDAI and correlated with the change in endoscopic findings; it decreased significantly between the 2-time points from a median of 661 ug/g IQR[425-1261] to 294 ug/g IQR[113-418] (p=0.02).

Both quality of life questionnaires (SIBDQ, IBD disk) improved significantly following antibiotic therapy: The median SIBDQ increased from 44 to 50 (p=0.02), and the median IBD disk score decreased from 59 to 31 (p=0.01) Figure 2 Panel B and C respectively.

Conclusion

FC is a sensitive and rapidly responsive biomarker of pouch disease activity, and we encourage its use when managing patients with pouchitis. Likewise, the SIBDQ and IBD disk accurately reflect change in QoL associated with change in disease state in patients with a pouch
P732 Impact of different types of physical activity in inflammatory bowel disease
Authors: Gofflot A , Monin L , Seidel L , Reenaers C , Kropp S , Van Kemseke C , Latour P , Forthomme B , Croisier J L , Louis E , Vieujean S
Published: January 2023

Background

Moderate physical activity (PA) appears to be beneficial for inflammatory bowel disease (IBD), improving the symptoms of the disease and promoting the maintenance of remission. However, little is known about the impact of different types of PA on IBD activity.

Methods

IBD patients with stable treatment without steroids for 4 months were prospectively included and randomized into 3 groups: muscle strengthening exercises, aerobic exercises, and a control group. The impact of a 10-week training period with 2 sessions per week was evaluated. Following parameters were collected: clinical activity of the disease (Mayo score for ulcerative colitis or UC, Harvey-Bradshaw index or HBI for Crohn’s disease or CD, patient reported outcome or PRO for both), Godin Leisure Time Exercise Questionnaire or GLTEQ (assessing PA level), Metabolic Equivalent Task or MET (assessing sedentarity level), barriers to PA, quality of life assessment (by EuroQol 5 dimensions or EQ5D and Short health scale or SHS), Inflammatory Bowel Disease Fatigue (IBD-F), physical abilities according to exercise stress test and maximum strength test.

Results

Between January 2021 and September 2022, a total 33 patients were enrolled in the program. Of these, 24 patients (13 women, 17 CD, median age of 31.6 [IQR, 29.4- 46.4]) completed the program and were included in the analysis (dropout rate of 18.2%). Table 1 shows the characteristics of these patients at inclusion. Eight, six and ten patients were respectively randomized in the muscle strengthening, aerobic exercise and control groups. After the training period, 50% of patients in the muscle strengthening group and 66.7% of patients in the aerobic exercise group showed a clinical improvement (according Mayo score and HBI). Strengthening was associated with significant reduction in PRO rectal bleeding in UC patients (p<0.0001) and aerobic exercise was associated with a significant lowering of HBI (p=0.039). Among the 24 patients, 2 CD patients relapsed in the muscle strengthening group during the training period. Aerobic exercise significantly reduced the barriers to PA (p=0.037). In neither group did we find any positive or negative impact of PA on quality of life or fatigue. Strengthening exercise and aerobic exercise significantly improved VO2max (maximal oxygen consumption) and Pmax in the exercise stress test, respectively. Most of the maximum strength tests were improved in the muscle strengthening group.

Conclusion

PA was well tolerated and associated with an improvement of disease activity in the majority of the IBD patients. There may be a variable impact of different types of PA in CD and UC, which should be explored further in larger cohorts.
P734 A single measurement of fecal calprotectin, particularly if combined with hemoglobin and C-reactive protein levels, predicts Crohn’s disease prognosis - a prospective study
Authors: Magro F , Estevinho M M , Catalano G , Patita M , Arroja B , Lago P , Rosa I , Tavares-de-Sousa H , Ministro P , Roseira J , Cancela E , Sousa P , Portela F , Correia L , Moreira P , Santiago M , Dias S , Afonso J , Danese S , Peyrin-Biroulet L , Dias C C
Published: January 2023

Background

Early flare prediction is essential for the timely management of Crohn’s disease (CD) patients, allowing to optimize the available therapeutic toolbox and to decrease the disease burden. We aimed to evaluate the performance of readily available biomarkers (when evaluated at least once or more frequently during follow-up) and to develop risk matrices to predict CD progression.

Methods

CD patients receiving infliximab (IFX) as maintenance therapy (n=289) were followed up for 24 months; those patients were enrolled in DIRECT, a prospective, multicenter real-world study. Disease progression was evaluated using two composite outcomes incorporating clinical and drug-related factors, the first including also IFX dose and/or frequency adjustments. Univariate and multivariable logistic regressions were used to calculate the odds ratios (OR) and to develop risk matrices.

Results

The isolated presence of anemia at least once during follow-up was a significant predictor of disease progression (OR 2.436 and 3.396 [p≤0.001] for composite outcomes 1 and 2, respectively), regardless of confounding factors. Levels of C-reactive protein (CRP) above 10.0 mg/L or fecal calprotectin (FC) above 500.0 µg/g, in at least one visit, were also significant predictors, while milder elevations (3.1-10.0 mg/L and 250.1-500.0 µg/g) were only relevant when found in at least two visits (consecutive or not). The risk matrices combining the different non-invasive biomarkers had a good ability to predict CD progression. Indeed, patients simultaneously presenting anemia, CRP>10 mg/dL and FC>500.0 µg/g at least once had a probability of disease progression that ranged between 42 and 63%.

Conclusion

The combined evaluation of FC, hemoglobin, and CRP in at least one time point and their incorporation into risk matrices seems to be the optimal strategy for CD management, as data from additional visits did not meaningfully influence the predictions and may delay decision-making. This is one of the first studies developing risk matrices to predict the occurrence of composite outcomes in CD patients, providing an easily applicable tool for CD clinical management.
P738 Surgery for Crohn’s Disease: Results from a Spanish cohort with 15 years of follow-up
Authors: Elosua Gonzalez A , Rubio S , Irisarri R , Campillo A , Nantes Ó , Vicuña M , Angós R , Zozaya J M , Rodríguez C
Published: January 2023

Background

Crohn’s disease (CD) is a lifelong disease. Knowing the natural history is essential to understand the evolution of the illness, assess the impact of different therapeutic strategies, identify poor prognostic factors and provide patients with understandable information who help them in decision-making. One of the most relevant features in natural history of Crohn’s Disease (CD) are surgery requirements.

Methods

We performed a retrospective study that includes all patients with a definitive diagnosis (DD) of CD in the Navarra Incident Cohort (which includes all patients diagnosed between 2001 and 2003 in Navarra, Spain). Our objectives were to analyze the cumulative incidence of surgical resection and to identify predictive factors for surgery.

Results

We included 94 patients with DD of CD (L1 46.8% / L2 17% / L3 36.2%) 49 were men, median age at diagnosis of 34 years (7-75) and with a median follow-up of 15.6 years.

At the end of the follow-up, 42.5% of the patients had undergone surgery, 33 (35%) intestinal resection, 7 (7.5%) surgery for perianal disease (PAD) and three (3%) for both reasons. In total 59 interventions were performed, 19 of them for PAD.

The cumulative incidence of intestinal resection in our series was 5.3% at diagnosis, 8.5% at one year, 22.4% at 5 years, 29.9% at 10 years, 44.6% at 15 years, and 68.3% at the end of the follow-up (fig A). In 82% of cases a single resection was performed and in 6 patients 2 resections were performed. The surgery was elective in 80% of the cases. Before the intervention, all had received corticosteroids or 5-ASA, 25% (8) immunomodulators and 21% (7) biological agents. The most frequent indication was symptomatic stenosis (45%) followed by inflammatory abscess (25%).

In the univariate analysis, age at diagnosis, sex, L4 involvement, extraintestinal manifestations, and Harvey-Bradshaw index were not associated to the probability of intestinal resection. Disease location and behaviour were associated with more probability of resection (fig B and C). In the multivariate analysis, penetrating behaviour (B3 vs B1) was an independent risk factor associated with resective surgery (HR 14.48; 95% CI 4.17-50.3; p <0.001) while ileocolonic disease (L3) was a protective factor compared with ileal location (L1) (HR 0.32; 95% CI 0.12-0.84; p = 0.02)

Conclusion

- In our cohort 5.3% of patients require intestinal resection at diagnosis and the cumulative incidence at 15 years of 45%

- Penetrating behavior was an independent risk factor for surgery and ileocolonic location a protective factor
P739 Sequential treatment is effective to achieve remission and avoid colectomy in moderate-to-severe Ulcerative Colitis refractory to anti-TNF therapy
Authors: Farkas B , Borsos M , Resál T , Bacsur P , Bor R , Bálint A , Fábián A , Szepes Z , Molnár T , Farkas K
Published: January 2023

Background

The development of anti-TNF agents has brought advances in the treatment of ulcerative colitis (UC). However, many patients require biological treatment sequencing. We aimed to evaluate clinical outcomes, the rate of treatment persistence and colectomy-free survival at second-, third-, and fourth-line therapy after switching from TNF-inhibitor to another treatment and to identify factors predicting the need for colectomy.

Methods

In this retrospective study, we included active UC patients refractory to at least one anti-TNF agent and needed treatment sequencing. The efficacy of therapies of the different lines was assessed by endoscopic or clinical scoring systems and laboratory markers. Kaplan-Meier analysis was performed to investigate the colectomy-free survival. Possible predictive factors were examined by logistic regression.

Results

Data of 90 UC patients were analyzed. The most frequently used first-line biologic therapy was infliximab (83.3%), which was discontinued after an average of 21.3 months. In the second-line vedolizumab (VDZ) was administered in 48.9% of cases, adalimumab in 36.7%. Average time between initiation and discontinuation was 15.7 months. In the third line, VDZ was used in 50%, tofacitinib in 29% of the patients, until an average of 8.7 months. In the fourth line, 53.1% of patients received tofacitinib and it was terminated after an average of 8.9 months. Loss of response, as a reason for treatment discontinuation was more common in the first-, and second-line therapies (58.9% and 46.2%), while primary non-response was more often observed in third-, and fourth-line therapies (52.6% and 63.6%). Fifteen patients underwent colectomy (16.7%). There was a significant increase in the probability of having surgery within 2 years after therapy initiation (p=0.0239) independently from treatment lines. Presence of deep ulcer showed inverse correlation with colectomy-free survival (p=0.0189; OR: 10.414 (95% CI: (1.472; 73.669)). Patients with high partial Mayo score at therapy initiation were more likely to undergo colectomy (p=0.0436, OR: 1.463 (95% CI: (1.011; 2.118)). In contrast, gender, age and disease extent at the time of the diagnosis, and the use of concomitant immunmodulators were not shown to be significant in predicting the subsequent surgical need.

Conclusion

Our results suggest that the remission rate does not decrease considerably as the sequential treatment progresses, more than half of the patients receiving fourth-line therapy were still in sustained remission. The more severe disease activity and deep ulcerations proved to be predictive for colectomy. Further studies in a larger patient population would be required to confirm our data and reveal predictive markers.
P740 Dual biologic therapy for patients with Inflammatory Bowel Disease in a single reference center in Spain
Authors: Diz Lois Palomares M T , Porta Sánchez Á , González Conde B , Estévez Prieto E , Vázquez Rey M T , Elberdin Pazos L , Alonso Aguirre P , Martin Herranz I
Published: January 2023

Background

In the last 5 years, the therapeutic arsenal in IBD has been expanded. Four different groups of effective biologic/new small molecules therapies, according to the target (anti-TNF, anti-integrin, anti-IL-12/23; and JAK inhibitors), are being widely used. There is still a significant number of patients who do not respond. In the last years, in tertiary centers, two simultaneous biologic therapies have been associated in a few IBD patients in clinical practice, in order to treat two different patient profiles: patients with IBD and concurrent extraintestinal manifestations (EIMs) which did not respond to the same biologic treatment, and second, refractory-IBD patients. It seems to add efficacy in case-series. However, safety concerns limit its use. We aim to describe the 6 patients treated in a single reference center in A Coruña, Spain.

Methods

The IBD Unit in A Coruña Universitary Hospital is the reference center for a 550000 patient population. Advance therapy with biologics is centralized in this IBD Unit, with approximately 630 patients having been treated with biologic therapy. Since 2020, we have treated 6 patients with dual biologic therapy (DBT), after discussing the case in the multidisciplinar IBD-Committee and with the informed consent of the patients. We describe this case-series.

Results

Our 6 patients proposed to DBT had long-standing IBD, and presented failure to 3-5 previous advanced lines of therapy. Two had ≥ 2 previous resection surgeries, and for 3 patients the surgery option would include a permanent stoma, or high risk of short bowel syndrome because of extensive disease.

We describe in table 1 patient’s demographics, IBD characteristics, and the DBT combinations.

In table 2 we further describe DBT and response to treatment.

Main indication for DBT was refractory IBD in 5/6 patients. DBT was intensified in all these cases. It added efficacy in 2/5 cases, however without achieving deep remission. Three patients (3/5) were co-treated with steroids. One patient had a serious infectious adverse event that required hospitalisation.

In 1/6 patient the indication for DBT was IBD and concurrent EIMs, each one responding to different biologic, this patient was initially co-treated with IMM and steroids; dual therapy was effective and safe, with standard doses.

Conclusion

Our experience is in line with that described by other authors. DBT in clinical practice is offered to long-standing and refractory IBD. In these cases, effectiveness seems limited, with concerns on infectious adverse events, but surgery probably carries worse prospects. For the indication of IBD with EIMs not responding to the same biologic, DBT seems more effective. More data is needed to know in which cases and what combinations could be beneficial.
P748 Pharmacokinetics, relative bioavailability, and dose proportionality of a tablet formulation of the sphingosine 1-phosphate-1 receptor modulator VTX002 (formerly OPL-002)
Authors: Gregg R , Yun C , Naik S , Huyghe M , Harris J , Mohan R , Nuss J , Sandborn W J
Published: January 2023

Background

VTX002 is an oral selective sphingosine 1-phosphate-1 receptor (S1P1R) modulator in clinical development for treatment of ulcerative colitis (UC). Single and multiple doses of a spray-dried dispersion (SDD) oral suspension of VTX002 were well-tolerated up to 45 mg in a phase 1 study in healthy participants and were accompanied by dose proportional reductions in lymphocyte counts, an expected pharmacodynamic outcome of treatment.1 A separate phase 1 study compared the pharmacokinetics (PK) and pharmacodynamics of the SDD oral suspension and a tablet formulation of VTX002.

Methods

Healthy adult participants (N=12) were randomised (4 per dose group) in an open-label 3-way crossover study to receive single oral doses of 5 mg or 20 mg VTX002 tablets, or 20 mg VTX002 SDD suspension followed by at least a 1-week washout between each dose as shown in Fig. 1. Study assessments included: VTX002 plasma concentrations, PK parameters, change from baseline in absolute lymphocyte count (ALC), and adverse events (AE).

Results

A total of 10 participants completed the study. Mean plasma VTX002 concentrations were greatest with a single oral dose of 20 mg VTX002 SDD suspension (Fig. 2).

The geometric mean peak (Cmax) and total (AUCinf) exposure to VTX002 were lower with the 5 mg (dose normalized to 20 mg tablet) and 20 mg VTX002 tablets compared to the 20 mg VTX002 SDD suspension (Table 1).

Geometric mean ratios for the tablet and SDD formulations of VTX002 are shown in Table 2.

Maximum percent (SD) reduction in ALC from baseline was greatest for the 20 mg VTX002 SDD suspension and was observed at 6 hours post-dose both for the SDD suspension and the 20 mg VTX002 tablet (59.9% [11.0%] and 51.6% [9.4%], respectively). The maximum percent reduction in ALC from baseline for the 5 mg VTX002 tablet was 22.4% (9.2%) which occurred 2 hours post-dose. A total of 23 AEs were reported; of which 19 were considered mild, and 4 were moderate.

Conclusion

All doses and formulations of VTX002 were well-tolerated and associated with ALC reductions. Data from this relative bioavailability study was used to convert the results from the prior phase 1 multiple ascending dose study performed with VTX002 SDD suspension to AUC equivalent tablet doses and enable tablet dose selection for phase 2. A phase 2 study of VTX002 tablets for treatment of UC is underway (ClinicalTrials.gov Identifier:NCT05156125).

1Luo A, et al. 2020 Gastroenterology. 2020;158(6):S1188.