bluuebunny/crossref_metadata_2025_split huggingface dataset:
P986 Effectiveness of the adjuvanted recombinant zoster vaccine (RZV) in preventing herpes zoster (HZ) among patients ≥50 years of age with Inflammatory Bowel Disease in the United States: A retrospective real-world database analysis from 2018 to 2021
Authors: Constenla D , Lonnet G , Aris E , Wang H , Rk R , Mwakingwe-Omari A , Yun H 
Published: January 2024

Abstract

Background
Patients with inflammatory bowel disease (IBD) are at higher risk of developing HZ compared to general population.1 The US Food and Drug Administration (FDA) approved RZV for adults ≥50 years of age (YOA) in Oct 2017 and for adults ≥18 YOA who are or will be at increased risk of HZ due to immunodeficiency or immunosuppression, as patients with IBD, in Jul 2021. This study addresses an information gap for RZV vaccine effectiveness (VE) in preventing HZ among IBD patients ≥50 YOA.

Methods
We conducted a retrospective matched cohort study using the Optum Clinformatics Data Mart healthcare administrative claims database from Jan 2018 to Dec 2021. Patients ≥50 YOA with IBD who received 2 RZV doses with dose interval ≥28 days (RZV [2-dose] cohort) were 1:3 matched to their unvaccinated counterparts (non-RZV cohort) by age, medication category, and other confounders (propensity score). The index date for RZV cohort was the date of the second dose and for non-RZV cohort was the same index date as their vaccinated match. Follow-up started from index date +30 days until earliest date of HZ occurrence, end of enrolment, death, receipt of HZ vaccine, or study end. The first HZ episode during follow-up was identified using an algorithm that included ICD-10 diagnosis code, inpatient or outpatient claims and/or HZ antiviral medication used within 7 days pre/post-HZ diagnosis. Incidence rates (IRs) of HZ were calculated overall, stratified by condition (ulcerative colitis [UC], Crohn’s disease [CD]) and age. Cox hazards models were used to estimate overall and stratified hazard ratios (HRs). VE (%) was calculated as (1−HR) × 100. A similar approach was used to evaluate VE for patients who received 1 RZV dose.

Results
We identified 6501 RZV vaccinated and 19962 matched unvaccinated IBD patients who were included in the 2-dose analysis (Table). The IR of HZ was 2.92/1000 person-years (PY) in the RZV cohort and 10.96/1000 PY in the non-RZV cohort, resulting in a VE of 73.4% (95% confidence intervals [CIs]: 60.8-82.0) for IBD patients (Figure). VE against HZ was 63.5% (95%CIs: 43.0-76.6) and 85.7% (95%CIs: 69.5-93.3) in UC and CD 2-dose cohorts. IRs and VE stratified by condition and age are presented in Figure. Adjusted VE for IBD patients who received 1 RZV dose was 63.4% (95%CIs: 24.9-82.2).

Conclusion
Our analysis provides real-world evidence that RZV vaccination is effective in preventing HZ in IBD patients ≥50 YOA and reduce the burden in this population with increased risk of HZ. These findings are consistent with the available literature on RZV effectiveness in patients with IBD, suggesting that this population could greatly benefit from RZV vaccination.
1. Yun H et al, Arthritis Rheumatol 2016;68:2328-37

Funding
GSK
P1004 Proportion of agents for refractory ulcerative colitis and the efficacy of immunomodulator in 5-aminosalicylic acid intolerance
Authors: Madarame A , Fukuzawa M , Naito S , Yamauchi Y , Yamaguchi H , Koyama Y , Kagawa Y , Ichimiya T , Shinohara H , Nemoto D , Itoi T 
Published: January 2024

Abstract

Background
5-Aminosalicylic acid (5-ASA) is effective for ulcerative colitis (UC), yet several patients exhibit intolerance to this medication. Although biologics and immunomodulators are often employed in cases of 5-ASA intolerance in UC, reports on their induction rates and effectiveness are sparse. This study aims to ascertain the proportion of therapeutic agents for refractory UC and evaluate the efficacy of immunomodulators in patients intolerant to 5-ASA.

Methods
We conducted a retrospective chart review of 182 consecutive UC patients treated for refractory UC at our tertiary referral hospital from 2014 to 2023. The 5-ASA intolerance group comprised patients who initiated oral 5-ASA therapy, discontinued one or more oral 5-ASA treatments within 6 months due to adverse effects, and were unable to continue oral 5-ASA therapy for over 6 months. Those who had been on oral 5-ASA for more than 6 months were categorised as the 5-ASA tolerance group. We compared the types of agents for refractory UC (immunomodulators, calcineurin inhibitors, anti-TNF-α agents, vedolizumab, ustekinumab, JAK inhibitors), disease duration, and clinical background (age at diagnosis, history of acute severe UC [ASUC], disease extent) between the groups. Additionally, we examined the discontinuation rates due to adverse effects and the continuation rate of immunomodulators.

Results
Among the patients treated with agents for refractory UC, 19 belonged to the 5-ASA intolerance group and 163 to the 5-ASA tolerance group. The time to initiation of treatment for refractory UC was significantly shorter in the 5-ASA intolerance group compared to the 5-ASA tolerance group (median 69 days vs 1431 days, p &lt; 0.001). The induction of immunomodulators occurred in 78.9% of the 5-ASA intolerance group, versus 38.0% in the 5-ASA tolerance group (p = 0.001). Anti-TNF-α agents was not used in the 5-ASA intolerance group, while 33.7% of the 5-ASA tolerance group received it (p = 0.001). 15 patients in the 5-ASA intolerance group and 53 in the 5-ASA tolerance group were introduced to immunomodulators to maintain remission. Discontinuations due to adverse effects were noted in 33.3% of the 5-ASA intolerance group and 18.9% in the 5-ASA tolerance group, but the differences were not significant. The one-year cumulative continuation rate of immunomodulators, excluding patients who discontinued due to adverse effects, was 93.3% in the 5-ASA intolerance group and 77.4% in the 5-ASA tolerance group, with no significant difference observed.

Conclusion
Immunomodulators are frequently introduced in cases of 5-ASA intolerance. No significant difference was found in the discontinuation rate of immunomodulators, with a high cumulative continuation rate observed in the 5-ASA intolerance group.
P1008 Efficacy and safety of retreatment with upadacitinib after treatment interruption in ulcerative colitis: Data from the phase 3 open-label extension study U-ACTIVATE
Authors: Panaccione R , Colombel J F , Dubinsky M , Hisamatsu T , Remple V , Garrison A , Klaff J , Kujawski M , Vermeire S 
Published: January 2024

Abstract

Background
Upadacitinib (UPA) is an oral reversible Janus kinase (JAK) inhibitor designed to preferentially inhibit JAK1 approved for the treatment of moderately to severely active ulcerative colitis (UC). UPA may be temporarily discontinued for many reasons including adverse events (AEs) and lack of efficacy.1 As clinical consequences of discontinuing and restarting UPA are yet to be characterised, here, we assess the efficacy and safety of UPA retreatment in patients (pts) who lost response following UPA treatment withdrawal.

Methods
Pts with a clinical response to 8 weeks’ (wks) UPA 45 mg once daily (QD; UPA45) induction therapy in the Phase 3 U-ACHIEVE or U-ACCOMPLISH studies were re-randomised to placebo (PBO), UPA 15 mg QD (UPA15) or UPA 30 mg QD (UPA30) for the 52-wk maintenance phase of U-ACHIEVE. Pts randomised to PBO who lost response could enter the long-term extension (LTE), U-ACTIVATE, and be retreated with UPA15. Efficacy was analysed (i) at wk 4 of the LTE and (ii) at wk 48 of the LTE among pts with an inadequate response to UPA15 who dose escalated to UPA30 between wks 2 and 36. Exposure-adjusted event rates (EAERs) of treatment-emergent AE (TEAE) were assessed throughout.

Results
Of 223 pts with a clinical response to UPA45 induction randomised to PBO during maintenance, 112 (50.2%) lost response (mean [standard deviation (SD)] days to loss of response: 135.4 [84.6]) and 110 subsequently entered the LTE. Pts with loss of response vs those without were more likely to have a history of inadequate response, loss of response, or intolerance to ≥1 biologic (57.1% vs 46.8%, respectively) or corticosteroid use at baseline (42.0% vs 33.3%). After 4 wks of retreatment with UPA15, 75/108 (69.4%) and 39/108 (36.1%) pts achieved clinical response and remission, respectively (Figure A). In total, 38 (34.5%) pts dose escalated to UPA30 (mean [SD] days to escalation: 80.3 [57.8]); 30/31 (96.8%) and 22/31 (71.0%) achieved clinical response and remission at wk 48 of retreatment, respectively (Figure B). For safety during maintenance, 225 pts with 128.7 patient-years (PYs) of exposure (loss of response [n=112], 42.6 PYs; no loss of response [n=113], 86.1 PYs) were analysed. Generally, the EAERs of serious TEAEs were numerically lower in patients with vs without loss of response. However, patient years of exposure were low, restricting interpretation. During the LTE, EAERs were generally similar in pts who underwent dose escalation vs all pts.

Conclusion
In pts who experience loss of response following UPA withdrawal, efficacy can be recaptured following retreatment with UPA15 and UPA30. No new safety signals were identified.
Reference
1. Sandborn WJ, et al. Gastroenterology. 2020;158(8):2139−2149.e14.
P1019 "Totality-of-the-evidence" of proposed ustekinumab biosimilar SB17"
Authors: Armuzzi A , Girolomoni G , Feldman S , Goncalves J , Park Y , Ye B D 
Published: January 2024

Abstract

Background
SB17 is a proposed biosimilar to Stelara [ustekinumab reference product (UST-RP)], which is a fully human IgG1/kappa monoclonal antibody to interleukin (IL)-12/23. In accordance with regulatory guidelines, "totality-of-the-evidence" proofs similarity between a proposed biosimilar and its reference product and includes analytical, non-clinical and clinical data.1, 2 SB17 is under review by regulatory agencies to be approved as ustekinumab biosimilar. The proposed justification for extrapolation of indications for SB17 was justified based on "totality-of-the-evidence" (i) MoA of ustekinumab binding to p40 subunit of IL-12/23, which has been associated with immune-mediated diseases, including approved indications of UST-RP (ii) overall data from the comparability comparison to UST-RP using analytical methods showing similar molecular structure and in vitro function (iii) PK studies showing similar exposure, and PD studies in healthy subject and (iv) efficacy and safety (including immunogenicity) based on studies in patients with moderate-to-severe psoriasis (PsO). The phase III study was conducted in ustekinumab-naïve patients with PsO as the most sensitive design to assess potential differences in efficacy and the risk of immunogenicity. The objective of this report is to describe the biosimilarity of SB17 to UST-RP with regard to potential extrapolation from PsO to other indications.

Methods
Analytical comparability of SB17 to UST-RP was assessed in ELISA binding assays. PK equivalence, efficacy, safety, tolerability, and immunogenicity similarity were assessed in clinical trials of healthy subjects and PsO patients.

Results
In the analytical assessment, SB17 was highly similar to the EU- and US-UST-RP in overall critical and non-critical quality attributes. Evaluation of IL-12 and IL-23 neutralization and binding activities, MoA-related biological activities, showed similarity between SB17, EU-, and US-UST-RP. 3
In a phase I study, SB17 and EU- and US-UST-RP had similar PK and comparable safety, tolerability, and immunogenicity (Table 1).4
In a phase III study of 503 patients with moderate to severe PsO, SB17 had equivalent efficacy and comparable safety and immunogenicity to UST-RP up to Week 28 (Table 1).5

Conclusion
With similar target binding and PK and confirmed similarity in efficacy and safety for PsO patients, SB17 is proposed to be highly similar to UST-RP in physicochemical, non-clinical, and clinical similarity studies. "Totality-of-the-evidence" data for SB17 supports its extrapolation to UST-RP indications.
P1020 Developing and Validating a Clinical Prediction Model Using Biomarkers to Assess Clinical Response and Severity of Crohn's Disease 12 Weeks After Initiation of Biological Therapy
Authors: Al-Ali A , Alamer A , Alomar M , Sharrofna A , Abualrahi D , Al Lehaibi L , Alothman A , Aldosari S , Alameel T 
Published: January 2024

Abstract

Background
Despite the evolution of therapeutic strategies for Crohn’s disease (CD), many patients exhibit resistance to numerous biological agents, necessitating a transition to other advanced therapies. Therefore, the early and accurate prediction of the response to biological agents in treating CD is crucial. We sought to evaluate potentially useful biomarkers in predicting clinical response to biological agents in the management of CD.

Methods
This retrospective cohort study included data from adult CD patients who were naïve to biological treatments and maintained regular follow-up at a tertiary referral hospital between January, 2017 to June, 2022. Two prediction models were built to predict the Crohn's Disease Activity Index (CDAI) response at 12 weeks in its ordinal scale. The two clinical models included age, gender, and previous CD surgery. In model-1, we included 8-weeks neutrophile-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) in their log scale as biomarkers of interest. Model-2 had 8-weeks neutrophile, platelet, monocyte, and lymphocyte counts in their natural scale. We built the prediction models using proportional odds model. Performance metrics were C-statistic for discrimination, brier score, visual calibration curve with bootstrap internal validation were used.

Results
A total of 104 patients were included, with a male predominance of 57.7% of the sample. The median age of the participants was 26 years (IQR: 21.00 – 36.00), and the median CDAI score was 237 (IQR: 125.25 – 256.0). Additionally, 43.3% of our population had undergone previous IBD surgery . The majority of the cohort initiated their treatment infliximab (59.6%), followed by adalimumab (35.6%). Model-1 has C-statistic of 0.678 compared to 0.682 for model-2. Brier scores for models 1 and 2 were 0.187 and 0.180, respectively. However, visual calibration curves showed better calibration of model-1 after bootstrapping internal validation corrected for over optimism. Odds ratio (OR) estimates of having higher odds of severe CDAI score at 12 weeks for model 1 were being female (OR: 2.20, 95% CI 1.04 –4.66; p = 0.04), higher NLR at week 8 (OR: 1.94, 95% CI 1.03– 3.65; p = 0.04), higher PLR at week 8 (OR 1.38, 95% CI 1.05– 1.8; p = 0.02), and higher CDAI score prior to the initiation of biological therapy (OR: 2.15, 95% CI 1.12– 4.13; p = 0.02).

Conclusion
The clinical prediction model that includes potentially useful biomarkers such as NLR and PLR at 8-weeks were well calibrated to predict a CDAI score at week 12 for the treatment response. Clinicians may find useful to implement prediction models in their clinical practice to evaluate the response of their patients.
P1034 The Egyptian ICRID-IBDQ: A novel IBD knowledge questionnaire from development and validation to comparison of different patient education modalities
Authors: Badary H A , Megally C , Anwar I , Hashem M B , Shehab H 
Published: January 2024

Abstract

Background
Inflammatory bowel diseases are chronic debilitating diseases whose proper management depends on patients’ good knowledge. It is the role of the physician to ensure good knowledge by tailoring appropriate methods of patient education.

Methods
This study included 105 patients with established diagnosis of IBD presenting to the Integrated Clinical and Research Center for Intestinal Disorders (ICRID) unit, Department of Endemic hepato-gastroenterology and infectious diseases, Faculty of medicine-Kasr Al Ainy Hospital, Cairo university. It included 2 phases: The first was cross-sectional analytical where the Egyptian “ICRID-IBDQ” questionnaire assessing the IBD patients’ knowledge was developed, validated, and used within the study population. This questionnaire comprised questions about the nature of the disease, lifestyle, diet, treatment modalities along with its effect on pregnancy and fertility; and the knowledge level was estimated by the number of correct answers considering scores above 75% as “Good”, 50-75% as “Fair”, and below 50% “Poor”. The second phase was comparative interventional where the patients were randomly allocated to 3 different educational methods: Direct education by physician, by infographic videos, and both combined, with the utility of the three in patient education compared using the ICRID-IBQ.

Results
The estimated patient knowledge of IBD is 26.3%, corresponding to “Poor”. The factors significantly associated with better knowledge on multivariate analysis are higher level of education (college or more) (p value &lt;0.001, OR 8.7), female gender (p value 0.002, OR 4.9) and positive family history (p value 0.042, OR 7.7). All fields had “poor” knowledge, and the field with the most defective knowledge was surgery. All patients receiving education improved, total percentage of improvement measured from 26.3% to 78.9% (p value &lt;0.001). There was no statistical difference between the 3 educational groups: Direct education by physician, infographic video or both combined (p value 0.09).

Conclusion
The importance of patient education has to be seriously addressed and tailored educational programs using combined methods have to be implemented by healthcare facilities to improve IBD patients’ quality of treatment and of life. Infographic videos are valuable tools which may aid in improving knowledge by patient education.
P1050 A cost-utility analysis of ferric derisomaltose versus ferric carboxymaltose in patients with inflammatory bowel disease and iron deficiency anaemia in Finland
Authors: Metsärinne K , Säävuori N , Ahmed W , Pollock-Wilkins R , Salminen K 
Published: January 2024

Abstract

Background
Anaemia is a common extraintestinal manifestation of inflammatory bowel disease (IBD), with iron deficiency being the most common cause. Iron deficiency anaemia (IDA) can be treated with oral iron, but where oral administration is contraindicated, not tolerated, or proves to be ineffective, intravenous (IV) iron is the preferred treatment option, facilitating rapid iron replenishment. Ferric derisomaltose (FDI) and ferric carboxymaltose (FCM) are two high-dose, rapid-infusion, IV iron formulations that have recently been compared in three head-to-head randomized controlled trials (RCTs), with FCM administration resulting in significantly higher hypophosphataemia incidence versus FDI, and phosphate monitoring after repeat FCM infusions is now recommended in the FCM product information (PI). Between 2000 and 2020, Finland has seen the average incidence of IBD increase by 2.4% annually, accompanied by a commensurate increase in sequelae such as IDA. The objective of the present study was therefore to evaluate the cost-utility of FDI versus FCM in patients with IBD and IDA in Finland.

Methods
A published patient-level simulation model was used to evaluate the cost-utility of FDI versus FCM in Finland. The model captured quality of life differences based on SF-36 data from the PHOSPHARE-IBD RCT and differences in the number of FDI and FCM infusions required. A Finnish societal perspective was adopted and the analysis was conducted over a five-year time horizon. Unit costs were obtained from publicly available Finnish sources. Costs were reported in 2022 Euros and a discount rate of 3% per annum was applied to future costs and effects.

Results
Over the five-year time horizon, patients received 3.95 courses of iron treatment on average, requiring 1.63 fewer infusions of FDI than FCM (5.57 versus 7.20). This resulted in iron procurement and administration cost savings of EUR 471 with FDI versus FCM (EUR 2,286 versus EUR 2,757). Differences in health-related quality of life and the number of IV iron infusions resulted in an increase of 0.076 quality-adjusted life years with FDI versus FCM. Further cost savings of EUR 273 over five years were also realised with FDI versus FCM, driven by reduced need for phosphate testing (saving EUR 90) and reduced travel and productivity loss (saving EUR 183). Total cost savings were EUR 745 (Figure) and FDI was therefore the dominant intervention.

Conclusion
Relative to FCM, FDI resulted in improvements in quality-adjusted life expectancy in Finnish patients with IBD and IDA. FDI also resulted in cost savings, arising from reduced infusion frequency, phosphate monitoring, patient travel, and productivity loss. FDI therefore represents the dominant choice of IV iron in Finnish patients with IBD and IDA.
P1052 High doses of methylprednisolone in inducing remission in acute severe ulcerative colitis
Authors: Marszk D , Treder A , Szlagatys-Sidorkiewicz A , Brzeziński M 
Published: January 2024

Abstract

Background
Ulcerative colitis (UC), characterized by mucosal inflammation progressing proximally through the colon, is increasing in incidence, including among pediatric populations. UC clinically manifests through symptoms such as abdominal pain, diarrhea, and hematochezia. Treatment aims primarily to induce and maintain remission. For those inadequately responding to 5-aminosalicylic acid, remission may be induced via oral steroids or, in severe instances, intravenous methylprednisolone (1.5mg/kg per day). This retrospective analysis aims to evaluate the efficacy of high-dose intravenous methylprednisolone pulses (30 mg/kg, max 1g per day for 3-5 days) in inducing remission in moderate and severe pediatric UC cases used in patients not responding to standard doses of steroids. In the fields of nephrology, rheumatology, oncology and neurology, the efficacy of high-dose glucocorticoids has been proven.

Methods
From a cohort of 121 pediatric patients (&lt;18 years) hospitalized 2018-2021 due to acute flare of UC, 15 were treated with high doses of methylprednisolone to induce remission. The Pediatric Ulcerative Colitis Activity Index (PUCAI) was used to determine the response to treatment- considering a 20-point reduction or a score below 10 as significant improvement and indicative of remission induction.

Results
The activity of the disease was moderate in 2 children and severe in 13 out of the analyzed group. We observed a clinically significant response in 9/15 patients (60%) with a mean PUCAI decrease of 30±23,4 points. The average duration to clinical remission was 4.06 days. For the 6/15 non-responders to methylprednisolone pulses, treatment was escalated (4 received infliximab, 1 adalimumab, and 1 initiated with cyclosporine followed by infliximab); notably, 3 required colectomy. Adverse effects were not observed during the treatment period.

Conclusion
In conclusion, high-dose methylprednisolone appears to be a viable alternative for inducing remission in pediatric UC. However, due to limitations such as the small patient group and the retrospective nature of this analysis, further prospective studies are essential to validate these findings.