bluuebunny/crossref_metadata_2025_split huggingface dataset:
P685 Effectiveness of a second-line anti-TNFɑ agent compared to a different mechanism of action after first anti-TNFɑ failure in ulcerative colitis: CambiaCU Study
Authors: López-Vico M , Hernández-Martínez Á , Soto-Escribano P , Rojas-Feria M , Cornejo-Jiménez A , Caballero-Mateos A M , Trapero-Martínez A M , Sánchez-Capilla A D , Cabello-Tapia M J , Martín-Rodríguez M D M 
Published: January 2024

Abstract

Background
Ulcerative colitis (UC) is a chronic and relapsing disease for which the number of biological therapies available are increasing over the years. Data comparing the effectiveness of a second anti-TNFɑ (aTNF) and the switch to a different mechanism of action (MoA) such as Ustekinumab (UST), Vedolizumab (VDZ), Filgotinib or Tofacibinib (JAK) is lacking.

Methods
We performed a multicenter and retrospective study (6 Andalusian sites) in which patients diagnosed of UC who had failed a first biological therapy with an aTNF and started a second-line biological therapy with another aTNF or a different MoA (UST, VDZ, JAK) were included. Clinical response and remission were assessed at weeks 16 and 52. The aim of our study was to evaluate the effectiveness of a second-line biological therapy with aTNF compared to a different MoA after a first aTNF failure.

Results
185 UC patients were included. There were no differences in the demographic data except for disease duration (9 years with MoA vs 13 years in aTNF, p=0.02). As first aTNF, infliximab (IFX) was the most common in both groups (49% MoA group, 56% second aTNF), followed by adalimumab (ADA) (48% MoA group, 33% second aTNF). In the second aTNF group, immunomodulators were significatively more used (60% vs 38%, p=0.003). There were no differences in the concomitant use of steroids. 80 patients received a different MoA (37 VDZ, 24 UST, 7 JAK) and 105 a second aTNF (34 IFX, 60 ADA, 11 golimumab). At week 16, 52% of patients were in clinical response (70% with another MoA vs 54% with second aTNF, p=0.07; IFX 65%, ADA 53%, VDZ 68%, UST 71%, JAK 74%, p=0.07), being 15.6% more likely to achieve response with another MoA. Clinical remission at week 16 was obtained by 36% (39% with another MoA vs 33% with second aTNF, p=0.6; IFX 47%, ADA 30%, VDZ 35%, UST 46%, JAK 37%, p=0.1). At week 52, 48% achieved clinical response (51% with another MoA vs 45% with second aTNF, p=0.8; IFX 50%, ADA 42%, VDZ 49%, UST 54%, JAK 53%, p=0.5) and 39% were in clinical remission (40% with another MoA vs 38% with second aTNF, p=0.53; IFX 50%, ADA 32%, VDZ 35%, UST 38%, JAK 53%; p=0.06) (figure 1). When the effectiveness is analyzed by first aTNF used, independently of the aTNF, subsequent use of a different MoA achieves better results although not significant compared to a second aTNF. Partial Mayo and calprotectin showed a significant decrease at weeks 16 and 52 in both groups. Hemoglobin and albumin levels remained similar during follow-up in both groups.

Conclusion
Second-line biological therapy is effective regardless of biological therapy used in UC, but switching to a different MoA tend to achieve better results in terms of clinical response and remission compared to a second aTNF.
P686 Comparison between therapeutic sequences starting with IV induction-biologic versus SC-induction biologic in bionaïve-patients with ulcerative colitis: results from the APPETISER study
Authors: Buisson A , M'Baye D , Pereira B 
Published: January 2024

Abstract

Background
Recent data suggest that infliximab and vedolizumab would be more effective than subcutaneous anti -TNF as 1st line-biologic, leading therapeutic sequencing challenging.
We compared the effectiveness of a strategy starting with a first-line bologic with IV induction (IFX or VDZ = IV group) compared to a biologic with SC induction (adalimumab or golimumab = SC group) to induce and maintain steroid-free clinical remission during the first 24 months.

Methods
From a database of IBD referral center, all consecutive UC patients ≥ 18 years-old who started a first line of biologic (IFX, VDZ, ADAor GLM) for active UC with follow-up &gt; 6 months were included. Prior colectomy or severe acute colitis were excluded.
The primary endpoint was remission defined according to PRO2 (PRO2-remission) as the absence of bleeding, normalization of transit (Mayo stool frequency subscore = 0) and no steroid. PRO2-remission was defined as a binary criterion each month (the statistical unit being the month and not the patient).
The secondary endpoints concerned the analysis by patient and were CFREM (partial Mayo score ≤ 2 without steroid) and endoscopic remission (CFREM + score Endoscopic Mayo ≤ 1) at week 12 .
All comparisons were adjusted using propensity scores on potential confounders. Analysis by month was performed using mixed models to account for repeated data.

Results
Overall, 130 patients were included including 60 patients in the IV group (IFX= 50 and VDZ= 10) and 70 in the SC group (ADA= 48 and GLM= 22). The populations had similar characteristics at baseline apart from concomitant immunosuppressant more frequent in IV group (55.9% vs 21.7%). 2nd line treatment was started in 26.7% of patients in IV group (ADA in 48.8%, VDZ 25.5% and ustekinumab 18.8%) and 87.1% of patients in SC group (IFX in 54.1%, VDZ 31.1%).
After adjustment, the rate of CFREM at week 12 was significantly higher in the IV arm (70.8%) than in the SC arm (33.0%) (p &lt; 0.001). The rate of endoscopic remission at W12 was 22.1% and 10.0% in the IV and SC arms, respectively (p =0.18).
In this study, 3350 months were analyzed (1180 in the IV arm and 1175 in the SC arm). The percentage of months spent in PRO2-CFREM in the first 24 months (primary endpoint) was greater in the IV arm than in the SC arm (74.2% vs 46.6%; p&lt;0.001). The percentage of months spent in CFREM was higher in the IV arm in the first 6 months (60.4% vs 18.9%), but also between M7 and M12 (73.1% vs 38.6%), M13 and M18 (79.9% vs 57.0%) or M19 and M24 (83.3% vs 64.6%) (p &lt; 0.001 for all comparisons).

Conclusion
A therapeutic sequence starting with IV induction biologic (IFX or VDZ) was more effective than starting with a SC induction anti-TNF (ADA and GLM ) to induce and maintain remission at short and long-term in UC.
P687 Ozanimod as a once-daily oral therapy for Japanese patients with ulcerative colitis: results from the induction period of a Phase 2/3 study (J-True North)
Authors: Matsuoka K , Nakase H , Fujii T , Hisamatsu T , Suzuki Y , Watanabe M , Uchikawa Y , Goto S , Fujimoto G , Zhang C , Hibi T 
Published: January 2024

Abstract

Background
Ozanimod is an oral, small molecule sphingosine 1-phosphate (S1P) receptor modulator that selectively targets the S1P1 and S1P5 receptor subtypes. Ozanimod is approved in multiple countries outside Japan for the treatment of moderately to severely active ulcerative colitis (UC) and/or relapsing forms of multiple sclerosis. We herein report the efficacy and safety results during the induction period of J-True North, a multi-centre, randomised, double-blind, placebo-controlled clinical Phase 2/3 study consisting of a 12-week induction period, followed by a 40-week maintenance period and an open-label extension period in Japanese patients with moderately to severely active UC.

Methods
Japanese male and female UC patients aged 18 to 75 years with moderately to severely active UC (defined as Mayo score of 6 to 12, with endoscopic subscore ≥2, rectal bleeding score (RBS) ≥1, and stool frequency score ≥1) were randomised in a 1:1:1 ratio to receive either 0.46 mg or 0.92 mg ozanimod, or placebo capsules orally once daily. All patients had received prior treatment with aminosalicylates or corticosteroids. The primary endpoint was clinical response at Week 12 (defined as a reduction from baseline in the complete Mayo score of ≥ 3 points and ≥ 30%, and a reduction from baseline in the RBS of ≥ 1 point or an absolute RBS of ≤ 1 point), and key secondary endpoints were clinical remission, clinical response, endoscopic improvement, mucosal healing and safety at Week 12 and 52.

Results
Patients were randomised to the ozanimod 0.46 mg group (n=68), 0.92 mg group (n=65), and the placebo group (n=65). At baseline, 36.4% of patients were female, mean age was 42.6 y and mean complete Mayo score was 8.4. The clinical response rate at Week 12 was 52.9%, 61.5%, and 32.3% in the ozanimod 0.46 mg, 0.92 mg, and placebo groups, respectively, demonstrating a statistically significant improvement of ozanimod vs placebo (Figure 1). Similarly, higher improvement rates were observed in all key secondary clinical and endoscopic endpoints in the ozanimod groups compared with the placebo group at Week 12. Frequent adverse events (AEs) observed in the induction period were nasopharyngitis, headache, et.al. (Table 1). AEs observed in the study were similar to those in the global phase 3 True North study with 0.92 mg ozanimod, and there were no new safety signals with ozanimod in the J-True North study.

Conclusion
Ozanimod as a once-daily oral therapy was effective as induction therapy for Japanese patients with moderately to severely active UC, and the safety profile was consistent with the results of previous studies.
Figure 1

Table 1
P689 Adaptive steroid tapering impedes corticosteroid-free remissions compared to forced tapering in UC clinical trials
Authors: Narula N , Hamam H , Wong E C , Marshall J K , Jairath V , Hanauer S B , Reinisch W , Dulai P S 
Published: January 2024

Abstract

Background
Protocols for managing steroids in clinical trials of ulcerative colitis (UC) vary. Most trials mandate steroid tapering at the beginning of maintenance phase. Adaptive steroid tapering allows for some discretion on whether to taper steroids for a patient. It remains unclear what impact steroid tapering protocols have on trial outcomes.

Methods
This post-hoc analysis from many clinical trials of advanced therapies in UC (VARSITY, ACT 1/2, PURSUIT, GEMINI1, OCTAVE and ULTRA2) was carried out under protocols with Vivli (00007656) and YODA (20224882). Responders to induction therapy with baseline corticosteroid use were considered as the primary population of interest. Adjustments were made to account for re-randomization designs and treatment exposure. Univariate analyses were conducted to identify baseline variables that had an association with the primary outcome of interest, one-year corticosteroid-free clinical remission (CR). All covariates with a significant univariate association (p &lt; 0.05) were considered for inclusion in the multivariate model. Logistic regression was used to assess the impact of steroid-weaning regimen on the outcome of interest. Secondary outcome of interest was one-year CR.

Results
There was a total of 861 patients from the seven included trials who had achieved clinical response after induction and were using corticosteroids. Within multivariate analysis, patients using adaptive steroid weaning regimens were less likely to achieve one year corticosteroid-free CR (odds ratio (OR) 0.66 (95% CI 0.48-0.92), p=0.015). Patients with higher partial Mayo scores were also less likely to achieve one year corticosteroid-free CR (OR 0.88 (95% 0.8-0.97), p=0.012). Other variables found significant on univariate analysis were no longer significant once considered within the multivariate model (smoking, race, albumin, endoscopic Mayo score). For the secondary outcome of one year CR, patients using adaptive steroid weaning regimens had increased odds for achieving one year CR as compared to those using fixed regimens (OR 1.9 (95% 1.43-2.52), p&lt;0.001). Several other variables were also found to have an association with one year CR within the multivariate model (Table 1).

Conclusion
Among patients with UC on corticosteroids at the time of study enrolment, adaptive steroid weaning regimens were less likely to achieve one-year corticosteroid-free CR but more likely to achieve one-year CR. This may help explain the findings within the VARSITY study, where patients treated with vedolizumab had increased odds for one-year CR but were less likely to achieve one-year corticosteroid-free CR. Consideration should be given to implementing mandatory steroid weaning protocols in future clinical trials of UC.
P693 Care needs and reasons for (not) seeking care among fatigued patients with Inflammatory Bowel Disease: A qualitative study
Authors: Bredero Q , ter Avest M M , Fleer J , Dijkstra G , Schroevers M J 
Published: January 2024

Abstract

Background
Fatigue is one of the most prevalent and burdensome symptoms experienced by patients with inflammatory bowel disease (IBD), even when the disease is in remission. Many patients report dissatisfaction towards fatigue-related care and uptake of available interventions is often low. This study aims to explore reasons why IBD patients do or do not engage in professional fatigue-related care and their needs regarding type of care and how to offer care.

Methods
We conducted a qualitative study, taking a phenomenological methodological approach. Sixteen adult IBD patients with disease in remission and severe fatigue (i.e., Checklist Individual Strength – subjective fatigue ≥ 35) were recruited from an academic hospital. We performed semi-structured interviews. Data were analysed using template analyses.

Results
We identified six themes regarding reasons why to (not) seek care for fatigue: 1) cognitions about fatigue and coping (e.g., a need to deal with fatigue alone), 2) perceptions of fatigue-related care and previous care experiences (e.g., perceiving that nothing can be done about fatigue), 3) knowledge and behaviour of the healthcare provider (e.g., fatigue complaints are not taken seriously), 4) somatic factors (e.g., physical symptoms of IBD), 5) social factors (e.g., feeling misunderstood by others) and 6) practical factors (e.g., time and money). Furthermore, we identified needs regarding how to offer care, i.e., proactive screening and active offer of care by healthcare providers, a holistic and person-centred approach and practical needs taken into account. Finally, regarding what care to offer, patients suggested a broad range of options, including information provision on fatigue management, eliminating physical causes of fatigue, discussing medication options, lifestyle support, psychological support, peer support and practical support.

Conclusion
IBD patients’ perceptions, coping and knowledge, as well as healthcare professionals’ behaviours play a major role in seeking fatigue-related care. Findings emphasize the importance of discussing IBD-related fatigue actively and taking a holistic and patient-centred approach to treat fatigue, targeting a broad range of physical- and psychological factors. These findings yield a better understanding of factors that hinder and facilitate care seeking in fatigued IBD patients and hereby provide ways to optimize the uptake of care.
P703 Comparison of infliximab and adalimumab therapies Persistence in patients with Ulcerative Colitis: Results from a Single Tertiary Turkish IBD Center Cohort
Authors: Eroglu Z , Yilmaz V , Guvenir T , Er R E , Toruner M 
Published: January 2024

Abstract

Background
In the last 25 years, the introduction of biological therapies has been a significant milestone in the management of inflammatory bowel diseases. Despite the recent emergence of new biological therapies and small molecules, Anti-TNF agents still play a crucial role in treatment. In a number of countries, anti-TNF agents are still reimbursed as a first line treatment following either a failure or intolerance to conventional therapies such as thiopurines and aminosalycilates. Many studies have been conducted previously to compare the efficacy of these drugs, but a clear conclusion could not be reached. In this study, we aimed to compare the persistence of infliximab (IFX) to adalimumab (ADA) in the treatment of ulcerative colitis at a tertiary IBD center in Turkey.

Methods
This was a retrospective cohort analysis of patients with ulcerative colitis either received adalimumab or infliximab as a first line biologic treatment. A total of 234 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 the 234 patients included in the study, 116 had used infliximab, and 118 had used adalimumab as a first-line treatment. Age and gender of the patients in both groups did not differ from each other statistically. 88% of the patients treated with adalimumab and 84% of the patients treated with infliximab were thiopurine experienced. Montreal classification did not differ between two groups (in IFX group, 73% of the patients had Montreal E3 involvement where as in ADA group, 66% of the patients had Montreal E3 involvement, p&gt;0.05). Primary non-response rates were not different between IFX and ADA group, 13.6% vs 13.4% respectively. In addition, clinical response rates after first year were 60% and 53% respectively. Drug persistency rates of adalimumab and infliximab in moderate to severe ulcerative colitis patients were not statistically different from each other (Figure 1).

Conclusion
Neither clinical efficacy rates nor drug persistency rates of adalimumab and infliximab in ulcerative colitis treatment were not different from each other. Factors such as age, gender, location of involvement, concomitant therapies, and smoking did not alter the outcome.
P704 Safety of Immunosuppression in A Prospective Cohort of Inflammatory Bowel Disease Patients with a HIstoRy of CancEr: The SAPPHIRE Registry
Authors: Axelrad J , Jiang Y , Colombel J F , Scherl E , Lukin D , Chang S , Chen L , Katz S , Kwah J , Swaminath A , Sultan K , Villagra C , Jandorf L , Itzkowitz S 
Published: January 2024

Abstract

Background
For patients with inflammatory bowel disease (IBD) and a history of cancer, retrospective studies have failed to find evidence suggesting that exposure to biologic and/or immunomodulator (IMM) agents was associated with new or recurrent cancer. The SAPPHIRE Registry was developed to prospectively examine this issue.

Methods
Patients with IBD who had a confirmed first (index) cancer 5 years prior to enrollment were recruited from centers affiliated with the New York Crohn’s and Colitis Organization (NYCCO) since 2016. Patients receiving chemotherapy or radiation therapy at enrollment or recurrent cancer within the last five years were excluded. The primary outcome was the development of an incident cancer stratified by IBD therapy exposure and adjusted for index cancer stage, index cancer type, sex, smoking history, and age at index cancer in a Cox proportional hazards model.

Results
302 patients were analyzed. Median age at IBD diagnosis was 31.5. Patients were 47% male, 88% white, and 61% never smokers. Index cancers were solid organ (138; 46%), dermatologic (100; 33%) GI (34; 11%), hematologic (27; 9%), or of other types (3; 1%); most index cancers (excluding non-melanoma skin cancer) were diagnosed as Stage 1. Following the index cancer, 90 (30%) patients were not exposed to any immunosuppression, and the other 212 were exposed to immunosuppressive therapy: 142 biologic monotherapy (anti-TNF, anti-integrin, anti-IL12/23, anti-IL23; 47%), 13 anti-metabolite monotherapy (mercaptopurine, azathioprine, methotrexate; 4%), 41 biologic + anti-metabolite combination therapy (14%), and 16 exposed to small molecules (JAK inhibitors, ozanimod; 5%). During follow-up, 46 (15%) patients developed subsequent cancers (25 new, 21 recurrent): 22 (48%) dermatologic, 15 (33%) solid, 7 (15%) GI, and 2 (4%) hematologic malignancies at a median age of 63.5. Patients not exposed to immunosuppression experienced incident cancer at a rate of 2.58/100 person-years (PY, Table). Those exposed to immunosuppression had a rate of 5.12/100 PY, representing an additional 2.54 cancers/100 PY (95% CI: 0.22, 4.85). In a time-varying Cox proportional hazards model adjusting for clinical and demographic characteristics, the adjusted hazard ratio for incident cancer for patients exposed to immunosuppressive therapy compared to unexposed patients was 1.36 (95% CI: 0.73, 2.52). Excluding non-melanoma skin cancer, the adjusted hazard ratio was 1.38 (95% CI: 0.66, 2.91).

Conclusion
In this ongoing prospective study, we have thus far found no association between immunosuppressive IBD therapy and risk of developing new or recurrent cancer. Ongoing enrollment and follow-up, specifically for individual drug classes and cancer types, are required to confirm these findings.
P709 Role of NOD2 single nucleotide polymorphisms on ustekinumab drug durability in adult patients with Crohn’s disease
Authors: Elleisy N , Behnisch S , Huth A , Schäffler H , Jaster R , Lamprecht G , Reiner J 
Published: January 2024

Abstract

Background
Ustekinumab (UST), a monoclonal antibody targeting the p19 subunit of the pro-inflammatory Interleukins 12 and 23, is a therapeutic option in patients with Crohn’s disease (CD) with high efficacy, although some patients will have to cease therapy with UST due to primary non-response, secondary loss of response, or adverse events. Single nucleotide polymorphisms (SNPs) in the Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) gene have been proposed as a prognostic factor in CD. Whether these NOD2 SNPs have an impact on UST drug durability among adult CD patients remains unclear.

Methods
CD patients were genotyped for the three most common NOD2 SNPs (rs2066844, rs2066845, and rs2066847). Hazard ratios (HR) for risk of NOD2 SNPs on UST durability were calculated using univariable and multivariable cox proportional hazard regression adjusting for age at first UST prescription, previous surgery, Montreal A, L, and B classification, present perianal disease, and previous anti-TNF exposure. Statistical analysis was conducted using SPSS. A two-tailed P value &lt; 0.05 was considered statistically significant. All patients provided written informed consent.

Results
92 CD patients were included in the analysis. Of those, 72 continued receiving UST until the end of the study. In univariable and multivariable analyses, NOD2 SNPs were not independent prognostic factors for UST drug durability (P&gt;0.05 for all three NOD2 SNPs). However, age at first UST prescription (adjusted HR [aHR] 0.96, 95% confidence interval [CI] 0.93-1.00, P=0.028 for all tested NOD2 SNPs) and present perianal disease (aHR 2.65, 95% CI 1.11-6.31, P=0.028 for all tested NOD2 SNPs) were independent predictors of ustekinumab drug durability.

Conclusion
Among adult Crohn’s disease patients being treated with ustekinumab, the presence of NOD2 SNPs did not have a significant impact on ustekinumab drug durability.