bluuebunny/crossref_metadata_2025_split huggingface dataset:
P827 Has opioid use increased among adults with Crohn’s disease? A Swedish Nationwide cohort Study 2008-2020
Authors: Osooli M , Bruze G , Bryder N , Nordenvall C , Myrelid P , Åsa Hallqvist E , Olén O 
Published: January 2024

Abstract

Background
Chronic opioid use has turned into a global health challenge. Crohn’s disease (CD) patients may experience severe pain requiring opioids which could exacerbate CD symptoms and pose a risk of chronic use. The use of opioids among CD patients has not been explored on a national level. We compared the secular trends of opioid use among prevalent CD patients and matched reference individuals in Sweden.

Methods
This nationwide cohort study included adults with a prevalent CD diagnosis who lived in Sweden for at least 12 consecutive months at some point between 1 January 2008 and 31 December 2020. For each patient, up to 10 reference individuals from the general population were matched on birth year, sex, calendar year, and place of residence. We retrieved the data on dispensed opioid prescriptions (opioid use) from the National Prescribed Drug Register. We defined opioid use as ≥1 filled prescription per calendar year. We also estimated the annual prevalence of ≥1 dispensation of weak (codeine combinations, tramadol, and Dextropropoxifen) and/or strong opioids (Oxycodone, Morphine, Hydromorphone, Fentanyl, Buprenorphine, Tapentadol, and Petidin).

Results
We identified 43,155 adult CD patients and 418,218 reference individuals (Table 1). The prevalence of opioid use was stable from 2008-2016. However, between 2017 and 2020 it decreased from 19.7% (95% CI: 19.2, 20.2) to 16.9% (95% CI: 16.2, 17.7) and from 8.5% (95% CI: 8.4, 8.7) to 6.9% (95% CI: 6.7, 7.1) among CD patients and reference individuals, respectively (Figure 1a). However, between 2008 and 2020, the prescription of strong opioids more than doubled among both CD patients (increasing from 4.3% [95% CI: 4.1, 4.6] to 11.5% [95% CI: 11.1, 11.8]), and reference individuals (increasing from 1.3% [95% CI: 1.3, 1.4] to 5.4% [95% CI: 5.3, 5.5]) (Figure 1b). In 2020, the last year of the observation, compared with males, both female CD patients (20.3% [19.7, 20.8] vs 9.3% [9.2, 9.5]) and their matched reference individuals (15.3% [14.8, 15.9] vs 7.1% [6.9, 7.2]) had a higher prevalence of annual opioid use. The secular trends of overall opioid use and increasing use of strong opioids were similar for males and females (data not shown).

Conclusion
Annual opioid use among prevalent CD patients in Sweden, a country with publicly-funded healthcare and access to modern CD treatment, was two-fold higher than in the general population in the last 13 years. The annual opioid use remained stable from 2008-2016 and slightly decreased from 2017-2020 for CD patients and reference individuals. During the same period, the use of strong opioids more than doubled for CD patients and the general population.
P843 Effectiveness and tolerability of methotrexate combined with biologics in patients with Crohn’s disease: A multicenter observational study
Authors: Park J , Jaeyoung C , Soo Jung P , Jae Jun P , Tae Il K , Hyuk Y , Jae Hee C 
Published: January 2024

Abstract

Background
Methotrexate (MTX) combination therapy with biological agents has gained increasing interest. Here, we assessed the efficacy and tolerability of the MTX combination therapy in patients with Crohn’s disease (CD).

Methods
We performed a multicenter observational study with 185 patients with CD with MTX and biologics combination therapy; the patients were recruited from three IBD Clinics in Korea. We evaluated the outcomes of the MTX combination therapy and examined the predictive factors of clinical and endoscopic remission.

Results
MTX was administered orally to 62.7% of patients; the mean dose was 15.5 mg per week, and the mean treatment duration was 36 months. Of the 169 patients treated with MTX combination therapy for over 6 months, the steroid-free clinical remission rates were 34.3%, 26.0%, 29.8%, and 32.7% at 4, 12, 18, and 24 months, respectively. Previous thiopurine use was a significant negatively associated independent factor (p &lt; 0.001), and a higher dose of MTX (≥15 mg/week) was a positively associated independent factor of steroid-free clinical remission (p = 0.035). Ninety-six patients underwent follow-up endoscopy after 28 months, and 36 (37.5%) achieved endoscopic remission. Longer disease duration (p = 0.006), ileocolonic type of Montreal location (p = 0.036), and baseline C-reactive protein (CRP) level of more than 5 mg/L (p = 0.035) were significant negatively associated independent factors and a higher dose of MTX (≥15 mg/week) was a positively associated independent factor of endoscopic remission (p = 0.037).

Conclusion
MTX combination therapy with biologics was effective and tolerable in patients with CD.
P862 Effects of induction and maintenance therapy with risankizumab on health-related quality of life outcomes in patients with moderately to severely active ulcerative colitis: A post-hoc analysis of Phase 2b/3 trials
Authors: Panés J , Loftus Jr. E V , Armuzzi A , Siegmund B , Sands B E , Boland B S , Kalabic J , Lai J H , Sharma D , Remple V , Sanchez Gonzalez Y , Lindsay J O 
Published: January 2024

Abstract

Background
Ulcerative colitis (UC) has a detrimental impact on patients’ health-related quality of life (HRQoL).1 Long-term treatment goals for patients with moderately to severely active UC include restoration of HRQoL. This post-hoc analysis evaluated the effect of induction and maintenance treatment with risankizumab (RZB) on HRQoL outcomes.

Methods
Data from two Phase 2b/3 clinical trials (INSPIRE induction: NCT03398148 and COMMAND maintenance: NCT03398135) were evaluated. Patients received RZB 1200 mg intravenous (IV) or placebo (PBO) induction treatment at weeks 0, 4, and 8. Patients with a clinical response per Adapted Mayo score to RZB IV were randomised 1:1:1 to subcutaneous (SC) RZB 180 or 360 mg, or placebo (PBO [RZB withdrawal] SC) every 8 weeks for 52 weeks of maintenance. The proportion of patients achieving a meaningful within-person change (MWPC) for each HRQoL outcome was reported. HRQoL outcomes included Functional Assessment of Chronic Illness Therapy-Fatigue, disease-specific instruments such as Inflammatory Bowel Disease Questionnaire (IBDQ) and Ulcerative Colitis Symptom Questionnaire (UCSQ), as well as generic quality-of-life questionnaires like Work Productivity and Activity Index-Ulcerative Colitis (WPAI-UC), 36-Item Short-Form Survey (SF-36), and EuroQoL 5 Dimensions 5 Levels. MWPCs were measured from baseline to induction Week 12 and to maintenance Week 52. Estimated differences in proportions with 95% confidence intervals and p-values between RZB and PBO were compared using the Cochran-Mantel-Haenszel test adjusting for baseline strata.

Results
For RZB 1200 mg IV (n=650) versus PBO IV-treated (n=325) patients, a greater proportion of patients achieved MWPC across all HRQoL outcomes at Week 12 of induction (p&lt;0.01; Table). At Week 52 of maintenance, a greater proportion of patients treated with RZB 180 mg SC (N=179) versus PBO (withdrawal) SC (N=183) achieved MWPC across all HRQoL outcomes (p&lt;0.05), except for absenteeism from WPAI-UC (p=0.33). For RZB 360 mg SC (N=186) versus PBO (withdrawal) SC, a greater proportion of patients achieved MWPC for UCSQ, IBDQ, and SF-36 physical component summary (all p&lt;0.05).

Conclusion
In this analysis, a greater proportion of patients treated with RZB versus PBO achieved MWPC on various HRQoL outcomes after completing 12-week induction IV therapy. HRQoL improvements were sustained up to Week 52 of treatment. This suggests RZB has the potential to help patients achieve restoration of HRQoL as a long-term goal of treatment in patients with moderately to severely active UC.
1. Mavroudis G. Therap Adv Gastroenterol. 2022;15:17562848211062406.
P871 A modified Crohn’s disease exclusion diet in a multi-ethnic Asian setting
Authors: Tan C K , Wong A , Huang Y , Ling K L , Wang L M , Ang T L , Ong J 
Published: January 2024

Abstract

Background
Crohn’s disease exclusion diet (CDED) has been shown to be well-tolerated and effective in adults with active Crohn’s disease (CD). There is limited data on using CDED in Asian setting. We performed this study to evaluate the feasibility and tolerability of using CDED as a nutritional intervention in Asian adults with CD.

Methods
We performed a prospective single centre observational study using 12-weeks of CDED as a nutritional intervention in adults with CD. The original CDED was adapted to foods commonly eaten in Asia. Patients with active CD were offered CDED as monotherapy or as an adjunct treatment to drug therapy. Dietary counselling was done by a dietitian and all food was prepared by individual participants or their family members. Participants were seen at baseline, week 6 and week 12. Dietary compliance was monitored by physician using direct questioning and, modified Medication Adherence Rating Scale (MARS) questionnaire. In addition, dietitian monitored compliance using 24-hour dietary recall and 3-day food journal. We monitor the disease activity using Harvey Bradshaw Index (HBI), C-reactive protein (CRP) and faecal calprotectin (FC). (Figure 1) The primary endpoint was tolerance to CDED; secondary endpoints were compliance to CDED and biomarker normalization. Intolerance was defined as refusal to continue with CDED and withdrawal from study. This study was approved by Singhealth Institutional review Board. Informed consent was obtained from all participants.

Results
A total of 6 participants were recruited from November 2022 to May 2023. Most participants were young. Four patients were on biologics (1 infliximab, 1 adalimumab, 1 vedolizumab, 1 ustekinumab). Two patients had CDED as monotherapy. (Table 1). All participants were able to tolerate 12 weeks of CDED and were mostly compliant to CDED. (Table 1) 5 of 6 patients had downward trend of CRP at week 12 compared to baseline and 4 of 6 had Two patients who received CDED as monotherapy had biomarker normalization at week 12. All patients were continued on CDED for another 12 weeks (maintenance phase).

Conclusion
Dietary intervention using CDED is well-tolerated among Asian adults with CD. More data is required to confirm the efficacy of CDED, both as monotherapy and in combination with drug therapy.
P879 Comparative Efficacy of Biologics and Small Molecule Therapies for the Induction and Maintenance of Endoscopic and Histological Remission in Ulcerative Colitis: A Systematic Review and Network Meta-analysis
Authors: Shehab M , Alrashed F , Alsayegh A , Aldallal U , Ma C , Narula N , Jairath V , Singh S , Bessissow T 
Published: January 2024

Abstract

Background
Treatment options for moderate to severe ulcerative colitis (UC) are increasing rapidly, but lack of comparative efficacy trials make treatment choices a clinical challenge. We aimed to compare the relative efficacy of biologics and small molecules in achieving endoscopic and histological remission in patients with moderate to severe UC.

Methods
The literature was searched between January 1990 and July 2023. Phase 3 placebo or active comparator randomized controlled trials (RCTs) were included to assess the efficacy of biologics or small molecule drugs as induction or maintenance therapies for patients with UC. The primary outcome was induction and maintenance of endoscopic improvement (Mayo endoscopic score ≤1), whereas secondary outcomes were the induction and maintenance of endoscopic (Mayo endoscopic score = 0) and histological remission. Sub-analysis was performed based on previous exposure to biologic therapy. We used a random effects model and reported data as odd ratio (OR) with 95% confidence intervals (CIs).

Results
We identified 34 studies that met our inclusion criteria, with a total of 12,227 patients with UC. Upadacitinib was superior to most biologics in inducing endoscopic improvement and remission as well as maintaining endoscopic improvement and histological remission. Etrasimod ranked second, after upadacitinib, in maintenance of endoscopic improvement in both biologic naive (80.4%) and experienced (78.9%) patients. Infliximab was superior to adalimumab (OR 1.88, 95% CI, 1.07; 3.29) and vedolizumab (OR1.85, 95% CI, 1.13; 3.03) in inducing endoscopic improvement in overall UC patients. Filgotinib 200 mg (OR 4.76, 95% CI, 1.89; 5.88) and vedolizumab (OR 4.16, 95% CI, 2.94; 6.25) were superior to adalimumab in maintaining histological remission. In biologic naive patients, infliximab was found to be superior to adalimumab (OR 1.80, 95% CI, 1.05;3.07), vedolizumab (OR 5.20, 95% CI, 2.04;7.69), and golimumab (OR 6.30, 95% CI, 3.39;9.71) in inducing endoscopic improvement

Conclusion
Upadacitinib appears to be superior to other therapies in achieving both endoscopic improvement and remission as well as maintaining histological remission. Furthermore, etrasimod, filgotinib and tofacitinib ranked high in achieving these outcomes. This study highlights the role of small molecules drugs as effective alternatives to biologics.
P888 Effectiveness and safety of Adalimumab Biosimilars in Bio-naive patients with Inflammatory Bowel Disease: The Galician experience
Authors: Vega Villaamil P , Vázquez Rey M T , Bastón Rey I , Ayude Galego M , Carmona Campos A , Baz López A M , Molina Arriero G , Ruiz Barcia M J , Regueiro Expósito C 
Published: January 2024

Abstract

Background
Biological drugs has revolutionized the management of inflammatory bowel disease (IBD). However, its use has led to a significant increase in cost that has strained health systems. Biosimilars will reduce cost related to treatment, allowing access to a greater proportion of patients. However, data on the efficacy and safety of the various ADA biosimilars in IBD patients "naive" to biologics remains scarce.

Methods
We performed an observational cohort study in 9 hospitals in Galicia. All patients with IBD naïve to biologics who started ADA biosimilar between November 2018 and January 2022 for control of their disease were enrolled. The primary endpoints were efficacy defined as clinical remission at week 8 and long term efficacy defined as persistence on drug treatment at the end of follow-up. The other co-primary endpoint was to determine the incidence of adverse events that lead to suspension or discontinuation of the drug or hospitalization of the patient

Results
384 patients (95 CU; 283 CD) with a median age of 47 (34-60) years and a median disease duration of 3.4 (0.8-10.0) years before starting treatment were included. After induction (at 8 weeks) 63.7 % of patients were in clinical remission and 85.0 % achieved clinical response. At this time of follow-up, 14 patients (4.9 %) discontinued treatment mainly due to primary non-response (PNR) (57.1 %) and adverse events (42.9 %). In total, 112 patients discontinued treatment during follow-up (Figure 1). The main reasons for stopping therapy were adverse events (32.1 %), PNR (30.4 %) and secondary loss of response (37.5 %). Clinical remission was maintained in 60.9 % of patients, after a median follow-up of 18 (12-24) months. Drug persistence shown by Kaplan-Meier survival curves were significantly higher in CD patients (p = 0.007) and in the group of patients treated with immunomodulators (IMM) (p = 0.001). Additionally, the rates of clinical remission and clinical response were higher in CD patients and in IMM-treated patients (Table 1). Adalimumab levels were also measured during follow-up, showing a median of 11 (6.8-14) μg/mL. Significantly, drug persistence was higher in patients with adalimumab levels ≥ 7 μg/mL at week 4 (p &lt; 0.001). Regarding treatment safety in this population, adverse events that required treatment suspension or discontinuation were reported in 36 patients.

Conclusion
Adalimumab biosimilars in usual clinical practice are safe and effective in inducing and maintaining remission in Galician patients with IBD. Drug persistence was significantly higher in patients with CD, treated with IMM and with post-induction ADA levels ≥ 7 μg/mL.
P891 Comparative Effectiveness and Safety of Infliximab and Tacrolimus in the Treatment of Acute Severe Ulcerative Colitis
Authors: Cohen N A , Tamir-Degabli N , Rozenfeld A , Hirsch A , Thurm T , Ron Y , Fishman S , Leibovitzh H , Maharshak N 
Published: January 2024

Abstract

Background
Acute severe ulcerative colitis (ASUC) affects approximately 20% of patients with ulcerative colitis (UC). Patients failing initial corticosteroid therapy receive salvage therapy with either infliximab (IFX) or calcineurin inhibitors, cyclosporine (CYS) or tacrolimus (TAC). We aimed to compare the effectiveness and safety of IFX and the oral calcineurin inhibitor, TAC, in this setting.

Methods
This retrospective cohort study included consecutive patients with ASUC, based on the Truelove and Witts criteria, admitted to Tel Aviv Medical Center between 2017 and 2022 and treated with salvage therapy. Demographic, clinical, and laboratory data were retrieved. The primary endpoint was successful salvage therapy defined as clinical response resulting in discharge without colectomy. Secondary endpoints included the colectomy rates at 90 days and the safety profile of the treatments.

Results
During the study period 96 patients with ASUC were admitted to our center. Of these, 40 patients received salvage therapy – 21 patients received IFX and 16 received TAC and were included in the analysis; 3 patients received CYS and were excluded from the study. Demographic data are detailed in Table 1. Disease duration was significantly longer in patients receiving TAC (mean (±SD) 9.7 years (±7.1) vs 4.5 (±5.9), p=0.04). In addition, patients receiving TAC had significantly greater prior exposure to advanced therapies (14 (87.5%) vs 6 (28.6%), p&lt;0.001) and 12 (75%) patients had previous exposure to IFX. Baseline markers of disease severity including disease extent, hemoglobin, C-reactive protein (CRP), albumin and body mass index (BMI) were similar between the treatment groups (Table 1). Therapeutic success was similar between treatment groups (IFX: 18 (86%) vs TAC: 15 (94%), p=0.62). The 90-day colectomy rate (IFX: 4 (19%) vs TAC: 2 (12.5%), p=0.68), CRP upon discharge (median (IQR) IFX: 15 mg/L (3.3-27) vs TAC: 11 mg/L (5.4-25, p=0.64) and length of hospitalization (mean (±SD) IFX: 23.5 days (±19.46) vs TAC: 17.56 days (±5), p=0.19) were similar between the groups. Safety profiles were similar between the treatment groups with mild electrolyte disturbances treated conservatively in both groups and no observed infections, deaths or other adverse events.

Conclusion
This real world, retrospective study shows that IFX and TAC have similar effectiveness and safety in the setting of ASUC. In this study, patients receiving TAC had significantly longer disease duration and advanced therapy exposure than those receiving IFX and still maintained excellent effectiveness highlighting TAC’s value in this setting.
P902 Subcutaneous infliximab (CT-P13 SC) as maintenance therapy for Crohn’s disease: 2 years results of the LIBERTY-CD study
Authors: Colombel J F , Hanauer S B , Sandborn W J , Sands B E , Schreiber S , Danese S , Kierkus J , Kulynych R , Klopocka M , Lahat A , Gonciarz M , Osipenko M , Borzan V , Kowalski M , Saenko D , Sardinov R , Lee S J , Kim S , Bae Y , Lee S , Lee S G , Yang S , Lee J , Park G 
Published: January 2024

Abstract

Background
CT-P13 subcutaneous (SC) infliximab formulation showed superiority over placebo as maintenance therapy at Week 54 in Crohn’s disease (CD)1 and ulcerative colitis2. The LIBERTY-CD study1 included an extension phase up to Week 102, the results, of which, are reported.

Methods
Patients who completed the maintenance phase up to Week 54 and, in the opinion of the investigator, would benefit from continued treatment could continue the open-label extension phase from Week 56 to Week 102 and received CT P13 SC 120 mg regardless of the previous assigned arm of maintenance phase. Patients who had received the adjusted dose of CT-P13 SC 240 mg during the maintenance phase continued receiving the same doses in the extension phase. At Week 54 and Week 102, clinical remission, clinical response, endoscopic remission, endoscopic response, clinical remission (alternative definition) and corticosteroid-free remission were assessed for patients who were treated CT-P13 SC during the extension phase (Figure 1.A) or who were treated CT-P13 SC during the extension phase and had valid efficacy results at the visit of interest (Figure 1.B). Patients with dose adjustment to CT-P13 SC 240 mg prior to Week 54 were considered as non-remitter/non-responder. Safety was evaluated through the extension phase.

Results
A total of 180 patients in the CT-P13 SC arm (assigned arm at the maintenance phase) entered into the extension phase. Overall, 85.6% (154/180) completed extension phase. Compared to the Week 54 results, efficacy results in the CT-P13 SC arm based on the non-responder imputation for missing or invalid data (i.e., patients who had missing or invalid data were considered as non-remitter/non-responder) were generally maintained in clinical remission, clinical response, endoscopic remission, endoscopic response, clinical remission (alternative definition), and corticosteroid-free remission at Week 102 (Figure 1.A). The efficacy results based on the no imputation for missing or invalid data (i.e., observed data) at Week 54 and Week 102 were similar (Figure 1.B). There was no new safety issue reported during the extension phase (Table 1). No death was reported during the extension phase.

Conclusion
Efficacy of CT-P13 SC was maintained through the extension phase. No new safety concerns were observed during the extension phase. These results show that CT-P13 SC provides both a long-term clinical benefit and safety with the convenience of SC administration for moderately to severely active CD patients.
[1] Colombel et al., Journal of Crohn's and Colitis, 2023.
[2] Sands et al., Journal of Crohn's and Colitis, 2023.