bluuebunny/crossref_metadata_2025_split huggingface dataset:
P543 Patients in trials of moderate-to-severe UC who are exposed to placebo are more likely to suffer harm than those receiving active treatment: The lack of clinical equipoise in traditional study designs
Authors: Fine Z , Fear E N , St-Pierre J , Klein J A , Choi N K , Rubin D T 
Published: January 2024

Abstract

Background
Ulcerative Colitis (UC) is a relapsing-remitting inflammatory disease of the colon and rectum. There are many challenges to the recruitment of eligible individuals into clinical trials for IBD, including the availability of multiple standard-of-care treatment options and patient refusal to participate in randomized placebo (PBO)-controlled trials due to fear of receiving PBO. Patient harm across clinical trials for moderate-to-severe UC has not been adequately examined. We sought to quantify the potential harm to patients recruited to PBO.

Methods
We reviewed phase 3 clinical trials of therapies for moderate-to-severe UC including anti-TNF-alpha (infliximab, adalimumab, golimumab), anti-integrin (vedolizumab), anti-interleukin (IL) 12/23 (ustekinumab), anti-IL23 (mirikizumab, guselkumab), Janus kinase inhibitors (tofacitinib, upadacitinib), and sphingosine-1 phosphate receptor modulators (ozanimod, etrazimod). We analyzed the proportions (# of pts. with events/cohort size) of adverse events (AEs), serious adverse events (SAEs), disease exacerbation AEs (DEAEs), and disease exacerbation SAEs (DESAEs). We calculated Number Needed to Harm (NNH = 1/Incidence rate in cohort) for PBO (NNHPBO) and experimental therapy (NNHRx) in each trial. Maintenance phase NNHs were categorized as treat-through (TT) or re-randomized (RR).

Results
We identified an increased probability of AEs in the PBO arm of 7/11 induction (NNHPBO= 2.18-11.06; NNHRx=2.47-16.52), 1/8 TT maintenance, and 5/11 RR maintenance (NNHTTPBO = 1.2-3.1; NNHTTRx =1.1-16.4; NNHRRPBO = 1.3-10.8). We identified an increased probability of SAEs for 8/11 induction (NNHPBO=14.5-58.0; NNHRx=22.13-101.0), 4/8 TT, and 5/11 RR (NNHTTPBO = 3.9-23.3; NNHTTRx =4.2-29.9; NNHRRPBO = 8.8-35.0). Patients were at increased probability of DEAEs in the PBO arm of 8/11 induction (NNHPBO=7.38-43.20; NNHRx=12.50-106.33), 7/8 TT, and 7/10 RR (NNHTTPBO = 3.0-11.1; NNHTTRx =4.3-15.0; NNHRRPBO = 2.7-25.2). DESAEs were at increased probability of harm in the PBO arm of 8/9 induction (NNHPBO=29.00-116.00; NNHRx=47.43-119.75), 3/5 TT, and 7/10 RR (NNHTTPBO = 14.4-52.0; NNHTTRx =13.2-230.0; NNHRRPBO = 11.2-25.2).

Conclusion
In PBO-controlled clinical trials of therapies for moderate-to-severe UC, there are increased AEs and SAEs for patients who receive PBO, especially for DEAEs and DESAEs. Induction treatment responders re-randomized for maintenance to PBO experienced greater harms (i.e. lower NNH) than TT PBO patients. These findings raise concern about clinical equipoise in moderate-to-severe UC clinical trials and support ongoing efforts to design trials with active comparator arms and adaptive or platform methodologies.
P551 Benefit–risk trade-offs and patient preferences for therapy selection in Ulcerative Colitis: a multi-country preference study
Authors: Gisbert J P , Schreiber S , Siegel C A , Magro F , Jus A , Whichello C , Michaels-Igbokwe C , Heidenreich S , Oortwijn A , Vermeire S 
Published: January 2024

Abstract

Background
The treatment landscape of ulcerative colitis (UC) is increasingly complex. In the absence of predictive biomarkers and objective parameters, shared treatment decision-making is advocated in clinical practice. This study quantified the benefit–risk trade-offs that patients with UC are willing to make when choosing a treatment. A patient-centric benefit–risk assessment of filgotinib, an oral, Janus kinase 1 preferential inhibitor, was also conducted to show how measured trade-offs can be used.

Methods
Patients recruited through databases, panels, social media and patient associations completed an online discrete choice experiment (DCE). Eligible patients were aged ≥18 years, had a diagnosis of UC for ≥6 months and resided in France, Germany, Italy, Spain or the UK. DCE treatment attributes were identified using a literature review, clinical data and patient interviews. Patients completed the DCE by choosing between a series of two hypothetical treatment options with varying attributes which were systematically varied to ensure trade-offs were made. Data were analysed using a mixed logit model. Relative attribute importance (RAI) scores and maximum acceptable risks were generated. Preference data were combined with SELECTION clinical trial data to evaluate the desirability of filgotinib 200 mg versus placebo from the patients’ perspective.1

Results
Among 631 patients who completed the survey (8997 patients invited), 75.3% were male and the mean age (standard deviation) was 42.2 (7.7) years. Patients preferred a daily oral pill over self-injection or intravenous treatment, and a treatment that avoided steroid use (Figure). Achieving and maintaining remission (RAI 32.4%; 95% confidence interval [CI] 29.5–35.2%) was considered the most important factor when choosing treatment. To achieve a 20% increase in the chance of remission, patients were willing to accept a 1.4% (95% CI 1.2–1.6%) increase in the risk of blood clots, a 2.0% (95% CI 1.7–2.3%) increase in the risk of serious infections, and a 0.7% (95% CI 0.6–0.8%) increase in the risk of malignancies (Table). Analysing patient preference and clinical data suggests filgotinib has a 70.1% chance of being preferred over placebo (p&lt;0.001).

Conclusion
Treatment preferences of patients were mostly driven by the likelihood of achieving and maintaining remission. To achieve this, they were willing to accept some increase in the risks of blood clots, serious infections and malignancies. Patients also valued avoiding steroids. A patient-centric benefit–risk assessment indicated that patients are significantly more likely to prefer filgotinib over placebo, illustrating how preference data can be used with clinical data to inform decision-making.
1. Feagan BG et al. Lancet 2021;397:2372–84.
P553 The safety and efficacy of adalimumab 80mg weekly as maintenance therapy in pediatric Crohn’s Disease
Authors: Cohen-Sela E , Weintraub Y , Yerushalmy-Feler A , Orlanski-Meyer E , Nassar R , Magen-Rimon R , Shamir R , Shouval D S , Matar M 
Published: January 2024

Abstract

Background
Intensification of adalimumab (ADL) dosing to weekly 40 mg injections, in response to low drug levels, has been shown to provide beneficial outcomes in pediatric patients with Crohn’s disease (CD). Our study aimed to evaluate the safety and efficacy of weekly 80 mg ADL administration in children with CD.

Methods
In this retrospective cohort study conducted across five Israeli centers, we reviewed the medical records of pediatric CD patients who received a high dose of ADL 80 mg weekly injections between 2016 and 2023. Collected data included demographic characteristics, disease features, laboratory studies, and treatment outcomes.

Results
Thirty-two children with CD were included: mean age 15.8 (±1.7) years at intensification, 21 male (66%), 18 (56%) with L3 phenotype. The median time to ADL 80 mg intensification from ADL induction was 48.4 weeks (IQR 23.1-122.5). The mean weighted Pediatric Crohn's Disease Activity Index (wPCDAI) was 28.5 (±16.9) at the time of intensification and the median calprotectin and C-reactive protein levels were 937 μg/g (IQR 540-1410) and 1.3 mg/dL (IQR 0.6-5.2), respectively. Clinically active disease was the main reason for ADL intensification (30, 94%). Baseline ADL levels were available in 30 patients (94%) with a median of 3.8 μg/mL (IQR 2.4-7.2). Among these, 23 children (77%) failed to achieve a target of ≥ 7.5 μg/mL. The median follow-up duration from the intensification dose was 91.2 weeks (IQR 53.6-149.1). Corticosteroids were required in 5/32 (15.6%) children, with a median time of 32.3 weeks (IQR 10.7-51.3) from intensification. There was no statistically significant difference in steroid utilization rates between children who achieved a target baseline drug level of ≥ 7.5 μg/mL and those who did not (p=0.934). Thirteen individuals (41%) discontinued ADL treatment, within a median of 24.7 weeks (IQR 11.7-57.1) from intensification. CD-related exacerbation, hospitalization, and surgery rates were 9 (28%), 4 (13%), and 2 (6%), respectively. No statistically significant differences were found in exacerbation (p=0.406), hospitalization (p=0.322), or surgery rates (p=0.427) between children who achieved a baseline ADL trough concentration level of ≥ 7.5 μg/mL and those who did not. Overall, ADL intensification was safe, but 3 (9%) patients developed new-onset psoriasis.

Conclusion
Our findings support the safety and efficacy of administering ADL at a weekly dosage of 80 mg as maintenance therapy in pediatric patients with moderate to severe CD.
P556 Immunomodulator and advanced therapies for Induction of clinical remission and response in Crohn’s disease: A systematic review and network meta-analysis
Authors: Sinopoulou V , Gordon M , Vuyyuru S , Darie A M , Radford S , Shale M , Moran G 
Published: January 2024

Abstract

Background
Several effective advanced therapies have been approved for the treatment of Crohn’s disease (CD) in the past two decades. Many have used synthesis techniques to study this area, but these rarely consider both advanced and immunomodulator therapy together in the same analysis. Network meta-analysis enables the direct and indirect comparison of these different therapeutic agents, aiding in determining their relative positioning within the treatment algorithm.

Methods
We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials between inception and October 2023 for randomised controlled trials (RCTs). The outcomes included were clinical remission and response, adverse events (AE), withdrawal due to AE, total and serious AE. We performed random-effects meta-analysis and network meta-analysis (frequentist approach), and estimated relative risk (RRs), 95%CI values. We used GRADE to ascertain certainty of evidence.

Results
A total of 83 RCTs comprising 19214 patients were eligible. A total of 28 interventions were included in the analysis. Combination of anti-tumor necrosis factor (TNF) and immunomodulators, anti-TNF monotherapy (adalimumab [ADA], infliximab [IFX], BI695501), IL-23 antagonists (ustekinumab [UST], guselkumab, risankizumab [RIS], mirikizumab), anti-integrins (vedolizumab, natalizumab) and upadacitinib were effective in inducing clinical remission compared to placebo (Figure 1). There was moderate certainty of evidence for combination of ADA and azathioprine (AZA) (RR 3.1, 95%CI [2.0-4.8]; risk difference [RD]: 40.1%), IFX+AZA (RR 2.5, 95%CI [1.7-3.8]; RD: 28.9%), ADA (RR 2.5, 95%CI [1.8-3.5]; RD:28.5%), and UST (RR 2.0 95%CI, [1.6-2.5]; RD: 19.2%) in induction of clinical remission compared to placebo. For induction of clinical response, there was moderate certainty of evidence for IFX+AZA (RR 2.8, 95%CI [1.6-4.8]), ADA (RR 2.5, 95%CI [1.7-3.9]), IFX (RR 2.8, 95%CI [1.6-4.8]), RIS (RR 1.9, 95%CI [1.3-2.6]). On analysis of serious adverse events all therapies were of no difference to placebo (very low certainty). On sensitivity analysis, the impact of concomitant immunomodulator use and the biological naivety of patients had little effect on these results.

Conclusion
On network meta-analysis, combination of anti-TNFs and immunomodulators followed by anti-TNF monotherapy had large effect size with moderate certainty for the induction of clinical remission. More novel therapies appear to have examples of similarly important effect sizes, but are currently limited due to the imprecision of the limited evidence base at present and future research should target these therapies in study.
P557 Data communication practices for reporting health care outcomes to improve quality of care: A scoping review
Authors: Ali M , Visser E , West R , Noord D V , Woude C J V D , Deen W V 
Published: January 2024

Abstract

Background
Value-based health care (VBHC) aims to improve care quality while minimizing costs. An important mechanism of VBHC involves monitoring and reporting health care outcomes to health care providers (HCPs) through data communication (DC) or data feedback. For complex diseases like Inflammatory Bowel Disease (IBD), unwarranted variation in care practices is ubiquitous. Health care data can be used to improve care by showing insights about achieved outcomes and practice variation to HCPs. While some tentative best practices for DC exist, a comprehensive overview is needed to gain a better understanding of how to effectively report health care outcomes to HCPs. This scoping review addresses this gap by examining the use and effectiveness of DC practices not only within the specific realm of IBD but also drawing insights from other clinical fields.

Methods
Studies that implemented and evaluated DC to engage HCPs with data and improve outcomes with qualitative or quantitative designs were sought. Medline, CINAHL, Scopus, Web of Science, Embase, the Cochrane Register of Controlled Trials and PsycINFO were searched for publications in English between 2010 - April 2023. Two researchers reviewed titles, abstracts and extracted data from eligible full texts.

Results
We screened 5,857 studies and included 239: 51 randomized controlled trials, 28 quasi-experimental, 121 pre-post intervention, and 39 qualitative studies. In 35% of those, feedback was implemented in acute care, 30% in primary care, 25% in tertiary care and 10% in other settings. Most interventions (76%) combined DC with co-interventions targeting HCPs’ intrinsic (providing education, post-feedback discussions) and/or extrinsic motivation (incentives, social influence). Additionally, 80 (33%) studies included nudges as part of co-interventions: action toolbox (n=38), reminders (n=28), posters to visualize compliance (n=12) and commitment messages (n=2). Best practices used in DC design included ‘benchmarking with peers’ (n=131), ‘timely feedback’ (n=141), and ‘active delivery of feedback’ (n=147). Most pre-post studies showed positive outcomes (96%), while only 63% of the studies with controlled designs showed positive improvements in outcomes.

Conclusion
The findings of our study highlight the use of DC (co-)interventions in various clinical fields. Additionally, we identified only few studies with controlled designs. In the future, studies with controlled designs testing the effectiveness of DC strategies and additive effects of different co-interventions are warranted to facilitate targeted improvements, particularly in the care of IBD patients, where care practices vary widely.
P561 Reasons for low use of topical 5-ASA formulations in patients treated for ulcerative colitis: comparison of doctors and patients perspectives
Authors: Pittet V , Rogler G , Seibold F 
Published: January 2024

Abstract

Background
Ulcerative colitis (UC) is a chronic relapsing inflammatory disorder of the colon. In patients with proctitis or left sided colitis, topical application of 5-ASA as suppository, enema or foam preparation has been shown more effective as compared to systemic treatment. In a study conducted 10 years ago, we observed an underuse of topical therapy in patients with UC.

Objectives
to assess the current use of topical 5-ASA for UC and compare it with previous findings. To evaluate perspectives on use of topical therapies, among physician and patients.

Methods
The study had two parts. We first conducted a retrospective cohort data analysis, among adult UC patients included in the SIBDCS. We included patients enrolled since 2012 (not included in our previous study), and to compare the results of the use of 5-ASA therapies from 2021-2021. We then conducted two parallel surveys: with patient and with gastroenterologists. The survey was independent from the cohort data analysis. We assessed potential reasons for low use of topical therapies.

Results
721 patients were included in the retrospective study (329 (45.6%) females, age at diagnostic (median, IQR): 31 (23-42), disease duration: 6 (2-15)). Disease extension at last FU was 18.0% proctitis, 26.3% proctosigmoiditis; clinical activity was low to moderate in 18.6%, and high in 1.8% of patients. 16.4% of patients with proctitis received topical 5-ASA only (5-ASA top+oral (5ASA): 42.2%), 5.9% with proctosigmoiditis (16.6% 5ASA), 0% in left-sided colitis (9.3% 5ASA) (figure 1). Exclusive 5-ASA topical use was lower than observed 10 years ago (23.3%) in proctitis. The survey was completed by 142 patients: 89 females (63%), mean (SD) age 46 (13) and disease duration 15 (10), 15% had proctitis/proctosigmoiditis and 29% left-sided colitis. 63 gastroenterologists participated in the survey; 25% were females, 36.5% had a professional experience up to 10 years, 55% were in single/group practice. 76% of patients reported having ever been prescribed suppositories (S), 74% foam (F), 61% enema (E). Patients-reported top reasons for stopping topical therapy prematurely (1/3 of cases) were unpleasantness (51.3% F/E, 13.9% S), ineffectiveness (41.1% F/E, 60.5% S), and preference for tablets (51.3% F/E, 37.8% S). Physicians’ perspectives on compliance difficulties were unpleasantness (83.7% F/E, 56.3% S), and preference for tablets (76.4% F/E, 63.7% S). 85% of patients were well informed on rectal therapies, 76% of doctors would be open for training/update on rectal therapies.

Conclusion
The use of rectal therapies in UC patients that should benefit from is still low. Reasons for non-compliance were discordant between doctors and patients.
P567 Impact of recent thiopurine use on ozanimod safety in patients with ulcerative colitis: a post hoc analysis of the phase 3 True North study
Authors: Battat R , Panaccione R , Hart A , Hisamatsu T , Ahmad H A , Osterman M T , Wu H , Jain A , Rosen M , Siegmund B 
Published: January 2024

Abstract

Background
Ozanimod, a sphingosine 1-phosphate (S1P) receptor modulator that selectively targets S1P1 and S1P5, is approved for the treatment of moderately to severely active ulcerative colitis (UC) in adults based on results from the phase 3 True North study (NCT02435992). Reductions in absolute lymphocyte count (ALC) are expected with ozanimod but not associated with treatment-emergent adverse events (TEAEs). This post hoc analysis explored the effect of recent use of thiopurines on ALC and safety outcomes in patients treated with ozanimod.

Methods
True North was a phase 3 trial of ozanimod induction and maintenance therapy in moderately to severely active UC. Patients in Cohort 1 were randomised to once-daily double-blind treatment with ozanimod 0.92 mg or placebo; patients in Cohort 2 received open-label ozanimod for a 10-week induction period. Patients on concomitant thiopurines were required to stop therapy at study start without a washout period. In this post hoc analysis, patients were stratified by recent prior thiopurine use (within 90 days of ozanimod initiation). ALC was assessed at baseline; ALC, TEAEs, and infectious outcomes were assessed during the induction period at Weeks 5 and 10.

Results
Of the 1012 patients in True North, 796 were treated with ozanimod and analysed (n=57 with recent thiopurine exposure; n=739 without recent thiopurine exposure). At baseline, mean ALC (×109/L [SD]) was slightly lower in patients with than without recent thiopurine use (Table). Both groups had similar baseline incidence of ALC &lt;200 cells/µL (0%) and &lt;500 cells/µL (range 0.0–0.3%). While ALC &lt;200 cells/µL and &lt;500 cells/µL were more prevalent among patients with than without recent thiopurine use (Figure), the reductions from baseline to Week 10 in ALC were similar in both groups (Table). Rates of infection were also similar in patients with recent thiopurine use (14.7% in Cohort 1 and 13.0% in Cohort 2) and without recent thiopurine use (10.4% and 12.5%, respectively). The most frequent infection was nasopharyngitis in both groups: 8.8% in Cohort 1 and 0% in Cohort 2 in patients with recent thiopurine use; 3.0% and 2.9%, respectively, in patients without recent thiopurine use. There were no serious adverse events (AEs) related to ozanimod treatment, and treatment discontinuations were similar in patients with and without recent thiopurine exposure.

Conclusion
Lower ALC was observed in patients starting ozanimod within 90 days of thiopurine use but was not associated with an increased incidence of infection or serious AEs. The findings suggest switching from thiopurines to ozanimod without a washout period may be safe and tolerable.
P580 Iron deficiency anaemia and quality of life in Inflammatory Bowel Disease: Prospective cohort study of ferric derisomaltose on quality of life and work productivity in patients with IBD
Authors: Goodhand J R , Parkinson M , Bewshea C , Ahmad T , Kennedy N A 
Published: January 2024

Abstract

Background
Iron-deficiency anaemia is a frequent complication of inflammatory bowel disease (IBD), affecting approximately 10% of patients at any one time. Quality of life scores in patients with IBD and anaemia are similar to those reported in malignancy. ECCO guidelines recommend assessment and treatment of iron deficiency anaemia, with a goal of normalising haemoglobin and iron stores.

Methods
We conducted a prospective observational cohort study of patients with IBD being treated for iron deficiency anaemia with ferric derisomaltose. Patients were included who were anaemic as per World Health Organisation criteria with a ferritin of &lt;30 µg/L and/or a transferrin saturation of &lt;18%. Variables collected included haematological parameters, the 12-item Short Form survey (SF-12) as a generic health-related quality of life measure, the Work Productivity and Activity Impairment (WPAI) questionnaire and the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) as a disease-specific quality of life measure. Patients were assessed at baseline, 12 weeks and 52 weeks. We present here the outcomes at week 12. Comparative statistics have been conducted using Wilcoxon signed rank tests and Pearson’s correlation coefficient.

Results
We recruited 124 patients given between 700 and 1900 mg of ferric derisomaltose, each as a single infusion. Of these, 60% (74/124) were female and the median age was 43 years (IQR 31 – 58). Just under half (46%) of participants had Crohn’s disease, the remainder had ulcerative colitis (49%) or IBD unclassified (5%). Median (IQR) baseline haemoglobin was 114 (109 – 123) g/L in men and 110 (104 – 116) g/L in women.
By week 12, haemoglobin, ferritin, SIBDQ, the WPAI, and both the mental and physical component scores of the SF-12 had improved significantly (all p values &lt;0.0001; see Figure 1). Change in the physical score of SF-12 correlated positively with change in haemoglobin (r = 0.38, p&lt;0.0001), while the change in WPAI correlated negatively with change in haemoglobin (r = -0.30, p=0.013).

Conclusion
Treatment with intravenous ferric derisomaltose in patients with iron deficiency anaemia and IBD was associated with significant improvements in haematological, work productivity, and quality of life parameters.