bluuebunny/crossref_metadata_2025_split huggingface dataset:
P483 Golimumab response in Ulcerative Colitis as early as week 2: What can we take from this?
Authors: Kumar L , O’Morain N , Sheridan J , Coe C , Egan C , Jones F , Cullen G , Doran P , Leyden J , Galligan M , McCarthy J , O’Toole A , Kevans D , Egan L , Doherty G ,   Investigator Network for Inflammatory Bowel Disease Therapy in Ireland (INITIative)
Published: January 2023

Abstract

Background
Golimumab is a monoclonal anti-TNF drug used in the treatment of Ulcerative Colitis (UC). GOAL-ARC is a multi-centered investigator initiated randomized control trial seeking to evaluate the utility of personalized Golimumab dose adjustment in UC versus standard dosing as per summary of product characteristics (SMPC) post-induction. From early analysis data, we aimed to ascertain if Golimumab induces response at 2 weeks and if this early response impacts disease activity at 6 weeks and the need for dose escalation at this interval.

Methods
Patients recruited to the trial were randomized to an intervention or a standard dosing arm. Golimumab was administered at 200mg at week 0 and 100mg at week 2 with assessments at weeks 0, 2, and 6. Baseline data was obtained including patient demographics and burden of disease. Outcomes measured were clinical response (defined by a decrease in partial mayo score of 2 points or a decrease of ≥30% from baseline), change in Faecal Calprotectin (FCP) as well as improvement in Short Health Scale (SHS) score and serum golimumab levels at 6 weeks. We also looked at FCP≤250μg/g (STRIDE II – intermediate treatment target) as an outcome.

Results
A total of 94 patients were recruited with 90 (95.7%) patients completing 2-week follow up and 79 (84%) patients completing 6-week follow-up. The median age was 37 years (IQR 28-46), 58.5% were male, and 76.6% (n=72) had a Mayo endoscopic subscore of 2 and the median DUBLIN Score was 4 (IQR 4-6).
At 2 weeks, a clinical response was observed in 68.9% of patients (n=62). There was a significantly lower median modified partial mayo score (2 vs 4, p&lt;0.001), rectal bleeding score (0 vs 2, p&lt;0.001), stool frequency score (1 vs 2, p&lt;0.001) and total SHS score (21.0 vs 25.8, p&lt;0.001) after 2 weeks of treatment. The median FCP was numerically lower (354.7μg/g vs 1111.5μ/g, p=0.207) with an overall reduction by 32.5%. Patients who achieved a clinical response at 2 weeks were noted to have a lower baseline total SHS score (23.9 vs 29.0, p=0.017). 2-week response did not correlate with 6-week outcomes.
Median FCP was significantly lower at 6 weeks (254.2μg/g vs 1111.5μ/g, p=0.008) with an overall reduction by 74.0%. There was a significantly higher median Golimumab level in patients with FCP≤250μg/g at 6 weeks (5.59μg/ml vs 2.41μg/ml, p&lt;0.001).

Conclusion
Golimumab shows efficacy in Ulcerative Colitis as early as 2 weeks with significant clinical response and a biochemical response. Early data suggests that response at 2 weeks, however, is not a reliable indicator of a sustained clinical response.
P488 Switch from intravenous to subcutaneous infliximab in patients with Inflammatory Bowel Disease: efficacy, safety and patients’ acceptance
Authors: Caballol Oliva B , Fernàndez-Clotet A , Panés J , Masamunt M C , Gallego M , Barastegui R , Vara A , Giner À , Ricart E , Ordás I 
Published: January 2023

Abstract

Background
A new formulation of biosimilar infliximab (IFX) has recently been approved for subcutaneous administration (SC) that may offer pharmacokinetic advantages resulting in higher drug exposure. Our purpose was to evaluate the efficacy, safety, pharmacokinetic changes and patients’ acceptability after switching from intravenous (IV) to SC IFX in a cohort of patients with Inflammatory Bowel Disease (IBD) in clinical practice.

Methods
Observational, prospective and single-center study including patients with IBD in sustained (≥6 months) clinical remission under IV IFX that were switched to SC IFX 120 mg every 2 weeks. Prospective monitoring was performed with clinical and laboratory data including IFX trough levels prior to the last IV infusion (W-IV), prior to the first SC administration (W-0), and after 16 weeks (W-16) and 52 weeks (W-52) of SC treatment. Patients’ satisfaction has been evaluated at W-52. A descriptive analysis of the data has been carried out with the R Studio statistical program using means and Wilcoxon signed rank test.

Results
Sixty patients have been included, all have achieved W-16 and twelve W-52. Thirty-five (58,3%) are men with a median age of 42,5 (20-71) years. Thirty-eight (63,3%) have Crohn’s disease and twenty-two (36,7%) ulcerative colitis, with a median disease duration of 11,3 years. They have been receiving IV IFX (5mg/kg/8 weeks in 95% of cases) for 5,7 (0,6-21,1) years, at a stable dose (≥6 months). Twenty-seven (45%) received concomitant immunomodulatory treatment and IFX was the first biological in 75% of patients. None of the patients presented clinical relapse during follow-up (Table 1). Median trough IFX levels under IV treatment were 3,9 µg/dl (W-IV) and 4,3 µg/dl (W-0). Compared to W-0, IFX trough levels were significantly higher both in W-16 [17,05 µg/dl (5,59–57,60), p&lt;0,005] and in W-52 [16,75 µg/dl (8,65 –35,01), p=0,007], without significant differences between W-16 and W-52 (p=0,74) (Figure 1). None of the patients developed immunogenicity. Three adverse effects have been detected: 1 allergic reaction to the first SC dose and 2 mild skin reactions. At W-16 and W-52 the number of patients maintaining SC IFX treatment were 58/60 (96,7%) and 10/12 (83,4%) respectively. At W-52, all patients expressed high satisfaction with the change and would not like to return to IV treatment. All place the SC route as a preference above the IV.

Conclusion
Switching from IV to SC IFX is safe, effective, and well accepted by patients with stable IBD. A significant increase in IFX trough levels is observed with the SC formulation.
P504 Guselkumab, an IL-23p19 subunit–specific monoclonal antibody, binds CD64+ myeloid cells and potently neutralises IL-23 produced from the same cells
Authors: Atreya R , Abreu M T , Krueger J G , Eyerich K , Sachen K , Greving C , Hammaker D , Bao P , Lacy E , Sarabia I , Deming J , Elloso M M , Ritchlin C , McInnes I B , Allez M , Fourie A 
Published: January 2023

Abstract

Background
Monoclonal antibodies targeting the interleukin (IL)-23p19 subunit are effective in the treatment of inflammatory bowel diseases (IBD), but have different molecular attributes that may translate to differences in clinical efficacy. Within this class, guselkumab (GUS) is a fully human IgG1 monoclonal antibody with a native Fc region, and risankizumab (RIS) is a humanised IgG1 antibody with a mutated Fc region. Binding of these therapeutic antibodies to Fcγ receptor (FcγR) I, or CD64, is of particular interest, as CD64+ IL-23-producing myeloid cells are increased in the inflamed colon in IBD and correlated with endoscopic disease severity (Chapuy L, et al. Mucosal Immunol. 2019; Chapuy et al. J Crohns Colitis. 2020). Here, we compared functional characteristics of the antigen-binding and Fc regions of GUS and RIS.

Methods
IL-23 binding affinity of GUS and RIS was compared in vitro using KinExA and surface plasmon resonance. In vitro cellular potency of GUS and RIS was measured by impact on IL-23-induced signal transducer and activator of transcription 3 (STAT3) phosphorylation in human peripheral blood mononuclear cells. Binding of GUS and RIS to FcγRs was assessed in cells transfected with individual FcγRs. In primary human “inflammatory” monocytes differentiated with granulocyte-macrophage colony-stimulating factor and interferon-γ (IFN-γ) followed by toll-like receptor stimulation to induce IL-23 production, binding of GUS and RIS to CD64 and capture of endogenously secreted IL-23 was assessed using flow cytometry. The potential impact of GUS binding to CD64 was assessed in IFN-γ primed monocytes using a human 41-plex cytokine bead assay.

Results
GUS and RIS displayed comparable picomolar binding affinity for IL-23 and equivalent high potency for inhibition of IL-23-induced STAT3 phosphorylation. GUS showed strongest binding to CD64 compared with other FcγRs, whereas RIS had negligible binding to any FcγR. GUS, but not RIS, showed dose-dependent Fc-mediated binding to CD64 in primary human “inflammatory” monocytes. Moreover, CD64-bound GUS was able to simultaneously capture IL-23 endogenously secreted from the same cells (Figure). GUS binding to CD64 on monocytes did not induce cytokine production.

Conclusion
GUS, but not RIS, can simultaneously bind CD64+ myeloid cells via its Fc region and neutralise IL-23 with high affinity and potency. Our in vitro data suggest a mechanistic benefit through enhanced localization of GUS within the inflamed colon, where CD64+ IL-23-producing myeloid cells are increased, and GUS can potently neutralise IL-23 at its source of production. These findings may contribute to differences in therapeutic profiles between antibodies.
P518 Safety of upadacitinib in ulcerative colitis: Long-term data from the phase 3 open-label extension study (U-ACTIVATE)
Authors: Panaccione R , Lichtenstein G , Nakase H , Armuzzi A , Kucharzik T , Levy G , Palac H , Kujawski M , Klaff J , Cheon J H 
Published: January 2023

Abstract

Background
Upadacitinib (UPA), an oral reversible and selective JAK inhibitor, has demonstrated efficacy, with a well-characterised safety profile, in two replicate induction studies of UPA 45 mg once daily (QD; U-ACHIEVE induction and U-ACCOMPLISH), and a maintenance study of UPA 15 mg or UPA 30 mg QD (U-ACHIEVE maintenance).1 Here, we report safety data from the ongoing, Phase 3, open-label, 288-week long-term extension (LTE) study in patients with ulcerative colitis (UC) who previously participated in the induction studies.

Methods
Rates of treatment-emergent adverse events (TEAEs) and TEAEs of special interest were calculated by treatment sequence in patients who received ≥1 dose of UPA in the induction studies, maintenance study, or by the data cut-off of 13 December 2021 in the LTE study. Rates are presented as exposure-adjusted event rates (EAERs; events/100 patient-years [PYs]), except for events that typically occur as a single instance, which are presented as exposure-adjusted incidence rates (EAIRs; n/100 PYs). PYs were calculated from the first dose of UPA 45 mg received during induction through to the last UPA dose received or the data cut-off date for ongoing patients.

Results
Overall, 1,308 patients representing 2,350.2 PYs of UPA exposure were evaluated (mean age: 43 years; female: 38%). Across treatment groups, EAERs of serious TEAEs, severe TEAEs, TEAEs leading to UPA discontinuation, TEAEs with reasonable possibility of being related to UPA, or TEAEs leading to death were numerically similar across all UPA treatment sequences (Table 1). EAERs of serious infections, herpes zoster, neutropenia, hepatic disorder, and creatine phosphokinase elevation were numerically higher with UPA 15 mg and 30 mg vs placebo; and creatine phosphokinase elevation with UPA 30 mg vs UPA 15 mg (Table 2). The EAER of anaemia was numerically lower with UPA 30 mg vs UPA 15 mg and placebo. Of note, no remarkable differences were observed in EAIRs of adjudicated major adverse cardiovascular events, adjudicated venous thromboembolic events, or malignancy (excluding non-melanoma skin cancer).

Conclusion: Long-term use of UPA 15 or 30 mg among patients with UC continuing to benefit from prolonged therapy representing 2,350.2 PYs of exposure was well tolerated. The ongoing safety profile of UPA is consistent with previous analyses, with no new safety signals identified compared with previous UC analyses following 52 weeks’ maintenance therapy,1,2 or other immune-mediated indications for which UPA is approved.3,4
P532 1-Year Clinical Outcome of Subcutaneous Infliximab compared with Intravenous Infliximab in Patients with Inflammatory Bowel Disease During Maintenance Therapy
Authors: Song J H , Hong S N , Kim E R , Kim J E , Chang D K , Kim Y H 
Published: January 2023

Abstract

Background
Although pharmacokinetic profile of subcutaneous infliximab (SC IFX) is superior to conventional intravenous infliximab (IV IFX), long-term efficacy and safety of SC IFX have not been compared with those of IV IFX in patients with inflammatory bowel disease (IBD). This cohort study aimed to evaluate the loss of response (LOR) and durable remission in IBD patients treated with SC IFX after switching from IV IFX compared with those in IBD patients who continued IV IFX.

Methods
This prospective cohort study enrolled 61 IBD patients with clinical remission who received scheduled IFX maintenance therapy from May to September 2022. Of them, 38 patients were switched to SC IFX with a shared decision-making between patients and physician. After dose optimization, they were followed up for one year. Clinical remission was defined as HBI &lt; 5 in in patients with Crohn’s disease (CD) and partial Mayo ≥ 2 in in patients with ulcerative colitis (UC). Biochemical relapse was defined as CRP ≥ 0.5 mg/dL in patients with CD and UC.

Results
LOR occurred in three (8%) patients of the SC IFX group and 5 (22%) patients of the IV IFX group, showing no significant difference between both groups (p = 0.140). The clinical and biochemical remission were not significantly different between the SC and IV groups (clinical remission: 20/23, 87% vs 33/38, 87%, p = 1.000; biochemical remission: 22/23, 96% vs. 34/38 89%, p = 0.641). The patients with IFX trough level &lt; 3 μg/mL was significantly lower in the SC IFX group (0/38, 0%) than in the IV IFX group (10/23, 43%; p &lt; 0.001). The incidence of IFX-related adverse events did not differ significantly between both groups (26% vs. 39%; p = 0.446).

Conclusion
SC IFX switch induced similar 1-year durable remission rate and safety profile with continuing IV IFX in patients with IBD during maintenance therapy. Pharmacokinetic profile was superior in patients treated with SC IFX compared with IV IFX.
P582 Efficacy of etrasimod at week 52 among subjects who reached clinical response at week 12: post hoc analysis of the phase 3 ELEVATE UC 52 trial
Authors: Vermeire S , Sands B E , Dubinsky M C , Feagan B G , Panaccione R , Jairath V , Yarur A , Chiorean M , Panés J , Goetsch M , Rabbat C J , Shah P , Wu J , Ghosh S 
Published: January 2023

Abstract

Background
Etrasimod is an investigational, once-daily, oral, selective sphingosine 1-phosphate receptor 1,4,5 (S1P1,4,5) modulator in development for the treatment of ulcerative colitis (UC). The ELEVATE UC 52 trial utilized a treat-through design which evaluated efficacy at week 52 among all subjects randomised from baseline. Here, we report a post hoc analysis of efficacy at week 52 among subjects who did or did not achieve clinical response at the end of the 12-week induction period in ELEVATE UC 52.

Methods
In ELEVATE UC 52 (NCT03945188), subjects (16-80 years) with moderately to severely active UC were randomised 2:1 to once-daily etrasimod 2 mg or placebo (PBO). This post hoc analysis assessed achievement of clinical remission, 12-week corticosteroid-free remission, endoscopic improvement, endoscopic improvement-histologic remission, and symptomatic remission at week 52 among subjects with baseline MMS 5-9 who did or did not achieve clinical response criteria at week 12 (defined as a ≥2-point and ≥30% decrease from baseline in MMS and a ≥1-point decrease from baseline in rectal bleeding subscore or an absolute rectal bleeding subscore ≤1).

Results
At week 12 in ELEVATE UC 52, 171 (62.4%) etrasimod-treated subjects vs 46 (34.1%) PBO-treated subjects achieved clinical response (P&lt;0.001) and were included in the week 52 clinical responder analysis. Among clinical responders at week 12, subjects treated with etrasimod were more likely to be in clinical remission at week 52 vs PBO (49.1% [n=84/171] vs 17.4% [n=8/46]; P&lt;0.001) (Figure 1). Similar results were observed for the achievement of all other efficacy endpoints at week 52 among those who met clinical response criteria at week 12 (all P&lt;0.05). At week 12 in ELEVATE UC 52, 103 (37.6%) etrasimod-treated subjects and 89 (65.9%) PBO-treated subjects either did not achieve clinical response at week 12 or had discontinued the study prior to the week 12 assessment. There were no significant treatment differences in achievement of efficacy endpoints at week 52 among subjects who did not achieve clinical response at week 12.

Conclusion
Among subjects who reached clinical response criteria at week 12, greater proportions of etrasimod-treated subjects vs PBO-treated subjects achieved week 52 efficacy across both objective and subjective measures of disease activity. Among subjects who did not reach clinical response or had discontinued prior to week 12, no significant treatment differences were observed at week 52 between etrasimod-treated subjects vs PBO-treated subjects. These results may help contextualize the 52-week efficacy results of ELEVATE UC 52 when considering other treatments that utilized re-randomisation of responder designs.
P613 Switch from intravenous to subcutaneous maintenance infliximab in real world IBD cohort
Authors: Mcgrory L , Goess C , Lynch K 
Published: January 2023

Abstract

Background
During the COVID-19 pandemic, there has been concern regarding patients attending hospitals for intravenous (IV) infusions due to increased COVID-19 exposure risk and demand on hospital resources. Data on switching patients from escalated dosing of IV infliximab (IFX) are limited. We describe a real-world experience of electively switching a cohort of patients on maintenance IV IFX for inflammatory bowel disease (IBD), at both standard and escalated dosing, to subcutaneous CT-P13 (Remsima®).

Methods
Adult patients with IBD on IV IFX at Royal Adelaide Hospital were invited to switch to fortnightly dosing of subcutaneous IFX. We collected demographic data using medical records, and prospectively measured clinical assessment scores (CDAI/HBI for Crohn’s disease (CD) and partial Mayo/SCCAI for Ulcerative Colitis (UC)), faecal calprotectin (FCal), CRP and trough IFX levels prior to switching to subcutaneous IFX, and at 6 months post switch. Clinical remission was defined as CDAI≤150/HBI≤4 (CD) or partial Mayo≤3 (no subscore&gt;1)/SCCAI≤2 (UC).

Results
29 patients were switched from IV IFX to subcutaneous CT-P13 between March 2021 and May 2022 (see Table 1 for baseline demographics). 23 had Crohn’s disease (79%). 10/29 patients (31%) were on intensified IV dosing at baseline prior to switch. The majority of patients, 25/29 (86%) were in remission pre-switch.
Of 19 patients with paired trough IFX levels, these increased significantly from baseline to 6 months post-switch (5.9mg/ml to 13.9mg/ml, respectively (p=0.0003), see Fig 1). The median FCal did not change pre- vs post switch (73mcg/g vs 80mcg/g, p=0.540), see Fig 2). Median CRP did not change pre- vs. post switch (1 µg/ml vs 2 µg/ml). Clinical assessment scores remained stable pre- vs. post-switch (CDAI 31 vs 31, (p=0.316) see Fig 3; HBI. 1 vs 2 (p=0.940); partial Mayo 0 vs 0, (p&gt;0.999); and SCCAI 1 vs 2 (p=0.5000)).
Regarding the subset of patients on escalated dosing at baseline, all patients were in clinical remission at 6 months post-switch. There was no significant change in IFX levels (8.4 vs 13.3, p=0.253). FCal did not significantly change (76mcg/g vs 79mcg/g (p=0.563), nor did median CDAI (37 vs 21 (p=0.5312) and median HBI (2 vs 2 (p=0.750)).
Overall, only 1/29 (3%) patients were not in remission at 6 month follow-up. No patients in required steroids or surgery. Of the 9 patients with perianal disease, none had a flare. All patients with weight&gt;100kg (n=4) remained in remission.

Conclusion
Switching patients from IV to subcutaneous IFX delivered stable clinical outcomes in this real world cohort, with no change in disease biomarkers and clinical indices. IFX levels increased overall and all patients on escalated IV dosing were in clinical remission at 6 months post-switch.
P618 Long-term real-world data of Ustekinumab in Ulcerative Colitis – the Stockholm Ustekinumab study – STOCUSTE
Authors: Sabhan H ,   C1 Lördal M2 Johansson F3 Bello F4 Muhsen S2 Wennerström C5 Forsberg O5 Borin A6 Almer S4 Höög C7 Söderman C1
Published: January 2023

Abstract

Background
Background: Ustekinumab (UST) is an anti-interleukin-12/23 antibody in the treatment of inflammatory bowel disease (IBD), mainly used in patients failing anti-TNF-agents. The STOCUSTE study includes patients treated at four hospitals in Stockholm to provide long-term real-world data.

Methods
Methods: This was a retrospective study including patients diagnosed with ulcerative colitis and treated with UST between years 2016 and 2021. The patients were followed from start of UST until withdrawal of treatment for any reason, or until end of study follow-up, July 31, 2021.We assessed disease activity; Physician Global Assessment (PGA); Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score, laboratory parameters and drug persistence. The primary outcome was remission (PGA = 0) and response (decrease PGA ≥ 1 from baseline) at 3 and 12 months, respectively.

Results
Results: 96 patients, 44 women and 52 men were included. The patients had either extensive colitis (68%), left-sided colitis (29%) or proctitis (3%). All but two patients were anti-TNF-experienced; 94 (98%) had failed ≥1, 59 (61%) ≥2 and 34 (35%) ≥3 anti-TNF-drugs. At inclusion 92 patients (96%) had active disease and 4 patients were in remission, 48 (50%) were on oral or topical corticosteroids, 13 (14%) had thiopurines. At 12 months only 9% were on oral or topical corticosteroids. Among patients who were treated with UST, 9/71 (6%) were in remission at 3 months, and 26/33 (78%) patients were in remission at 12 months. Withdrawal from treatment during the first 12 months was 36 (38 %), mainly due to persisting disease activity (20%); 8% were withdrawn due to adverse events, 2% needed bowel surgery, and 2% were lost to follow up.

Conclusion
Conclusions: In this group of difficult-to-treat patients with ulcerative colitis, Ust was shown to be effective in the majority, with high drug persistence at 12 months in combination with a favorable safety profile.