Induction Period Research Articles

Detoxification of Carbonaceous Species for Efficient Perfluorocarbon Hydrolysis.

Thermocatalytic hydrolysis of perfluorocarbons (PFCs) is a promising way to reduce their emission and environmental hazards. However, hydrolysis of PFCs, such as CF4, usually suffers from a drastic activity decline during the induction period, which seriously hinders its conversion performances and practical applications. In this work, we found that the carbonaceous (*COO) species account for the activity decline during the induction period, and their detoxification could promote PFC hydrolysis at low temperature. In situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) shows that the poisoning signals belong to *COO species on the surface of γ-Al2O3 during CF4 catalytic hydrolysis. The adsorption configuration of *CFOH intermediate is the key to the formation of poisoned *COO species. By introducing Ni sites with strong *CFOH adsorption capacity into γ-Al2O3, the *CFOH at the Al active site can transfer to the adjacent Ni site to avoid the formation of poisoned *COO species, which was proved by DRIFTS and density functional theory. As a result, the optimal 0.1Ni/γ-Al2O3 (10% Ni loaded γ-Al2O3) catalyst achieved 100% CF4 conversion without any activity decline at 570 °C for over 300 h, much higher than that of ∼55% CF4 conversion on pure γ-Al2O3 at the same temperature. This work provides new insights into the detoxification of thermocatalytic PFC hydrolysis at low temperatures.

Effect of lecithin on the antioxidant mechanism of action of fucoidan in stripped bulk sunflower oil and respective oil in water emulsion.

The objective of this study was to investigate the antioxidant mechanism of action of fucoidan in sunflower oil and its oil-in-water emulsion. In addition, the effect of lecithin on the antioxidant mechanism of action of fucoidan in sunflower oil was investigated. In sunflower oil, fucoidan at 0.02% (w/w) concentration showed the highest induction period (591.02h), while in sunflower oil-in-water emulsion, fucoidan at 0.04% (w/w) concentration showed the highest induction period (141.57h). In addition, the induction period of sunflower oil samples containing fucoidan with lecithin was higher than those without lecithin. Evaluating the mechanism of action of fucoidan in sunflower oil and its oil-in-water emulsion indicated that fucoidan took part in the initiation chain's side reactions and the major termination reaction. The interfacial tensions of samples containing lecithin were significantly lower than those without lecithin. In addition, the reverse micelle size of samples containing lecithin was considerably lower than those without lecithin. Therefore, lecithin enhanced fucoidan's effectiveness by decreasing interfacial activity and increasing the capacity to incorporate lipid hydroperoxides within the structure of reverse micelles. The water produced during oxidation played an essential role in the antioxidant potency of fucoidan. Taken together, lecithin significantly enhanced the antioxidant activity of fucoidan by improving its interfacial activity in sunflower oil.

Gibberellin Treatment Toward Off-crop Season as a Practical Tool to Increase Yield in ‘Orri’ Mandarin

Multiannual fruit bearing in fruit trees varies from regular bearing, with an almost steady yield from season to season, to alternate bearing, during which a year with a high fruit load (on-crop) is followed by a year of a low fruit load (off-crop). ‘Orri’ mandarin [Temple (Citrus temple hort. ex Y. Tanaka) × Dancy (Citrus tangerine hort. ex Tanaka)] exhibits a nonregular bearing pattern: steady for a few years and alternate for others. In nonregular or alternate-bearing cultivars, fruit load is thought to regulate flowering induction and development negatively the following year. In citrus, the bud meristem develops into a leafless inflorescence (generative), leafy inflorescence (mixed type, containing leaves and flowers in various ratios), or vegetative shoot, or remains dormant. Mixed-type inflorescences contribute to most of the final yield. Gibberellins inhibit flowering when applied at relatively high concentrations during the flowering induction period in the winter, but they are suggested to induce yield when applied at relatively low concentrations. We determined the effect of mild gibberellin application in an off-crop year on the productivity of ‘Orri’ mandarin, and whether it occurs through the induction of mixed-type inflorescences. Low-concentration, low-frequency gibberellin treatments were applied to trees during the winter when fruit load was high, resulting in a greater number of mixed vs. generative inflorescences at anthesis. An average increase of 40% in fruit number and yield weight was recorded in off-crop seasons at harvest, whereas no change was recorded in on-crop seasons. We discuss treatment efficiency in on-crop and off-crop years as a practical tool for increasing yield in low-crop seasons of ‘Orri’ mandarin.

Study on the Mechanical Properties, Tensile Performance, Hydration Heat, and Microstructure of VAE-Modified Rubber Mortar

This study builds on the practice of using waste rubber to improve the ductility of cement mortar and further explores the potential of vinyl acetate-ethylene (VAE) in enhancing the ductility of rubber cement mortar (RM). It systematically analyzes the effects of VAE on the workability, mechanical properties, crack resistance, and microstructure of RM. Additionally, isothermal calorimetry was employed to investigate the mechanism of VAE's influence on cement hydration heat. The results show that VAE significantly improves the flexural strength, tensile strength, and ultimate tensile strain of RM, while reducing its compressive strength and tensile elastic modulus, thereby markedly enhancing its flexibility and ductility. At a VAE content of 4%, the fluidity, 28-day flexural strength, tensile strength, and ultimate tensile strain of RM reached 240 mm, 4.83 MPa, 1.92 MPa, and 233×10⁻⁶, respectively, representing increases of 16%, 18.97%, 11.63%, and 62.94% compared to ordinary RM. However, when the VAE content exceeded 4%, both flexural strength and tensile strength began to decrease. Furthermore, the incorporation of VAE induced the formation of flexible polymer films within the RM matrix but also increased the porosity of the cement matrix, extended the induction period of cement hydration, and reduced the rate and degree of hydration. These findings provide valuable data to support the development of high-ductility and high-crack-resistance concrete repair materials.

Multi-Scale Modeling of Transport Properties in Cementitious Materials with GO Admixture

In coastal areas, the presence of concrete cracks provides pathways for hazardous ions to ingress from the exterior into the interior of concrete, while the migration of the ions further accelerates concrete deterioration and causes durability problems. The incorporation of graphene oxide (GO) into concrete can inhibit crack initiation and development starting at the nanoscale, improving the concrete microstructure, thereby affecting concrete’s resistance to hazardous ion transport and the resulting deterioration. In this study, a multi-scale transport model for cementitious materials with a GO admixture was established to predict the resistance to hazardous ions. Based on the determination of hydration types and hydration kinetics, microstructure modeling was conducted at three scales, the sub-microscale, microscale, and mesoscale, upon which transport property simulations were performed. At the microscale, the effects of both the cement paste matrix and the interfacial transition zone (ITZ) were considered. Through the simulation, it was found that the addition of GO reduced the duration of the induction period and increased the rate of hydration development after the induction period. Moreover, the incorporation of GO could reduce the porosity of cementitious materials at all simulation scales at both early and later ages. At the microscale, it improved the pore structure of the cement matrix and ITZ by reducing large pores and increasing small pores. At all three simulation scales, GO could increase the diffusion tortuosity in hydration products, suppress ion transport, and improve the resistance to hazardous ions of cementitious materials.

Effects of Gamma-irradiation on Fatty Acids and Oxidative Stability of Oil from Treated Walnuts. Impact of Antioxidant Compositions on Oil Autoxidation

Gamma-irradiation at doses of 10 kGy and 25 kGy was applied on walnuts in order to study changes in the fat yield, fatty acids composition, conjugated dienes and trienes, tocopherols and oxidative stability of the extracted glyceride oils. The results revealed no significant changes in fat yield and fatty acids composition but an increase of dienes and trienes, and a decrease in tocopherols amount. Decrease of Induction periods of oils autoxidated at 80 ⁰C, 100 ⁰C, and 120 ⁰C was observed as well. In order to reduce the negative effects of radiation-related lipid oxidation walnut oils were supplemented with binary antioxidant mixtures. Thus, the composition of ascorbyl palmitate and α-tocopherol in 2:1 ratio slightly prolonged the induction periods while halving of the initial oxidation rate of oils extracted from irradiated walnuts at the same time.

Techno‐Economic Evaluation of Synthetic and Natural Antioxidants Used for Enhancing Oxidation Stability of Biodiesel

ABSTRACTThe oxidation stability of biodiesel is a critical factor affecting its storage and performance, necessitating the use of antioxidants to enhance its shelf life and reliability. Both natural and synthetic antioxidants have proven effective in improving the oxidation stability of biodiesel, with numerous studies demonstrating their ability to extend the induction period and delay oxidative degradation. However, while the technical efficacy of these antioxidants is well‐documented, the techno‐economic analysis that evaluates the cost‐effectiveness of using natural versus synthetic antioxidants remains unexplored. This creates uncertainty in selecting the most sustainable and economically viable antioxidant option. This study aimed to conduct a techno‐economic analysis comparing the cost‐effectiveness of synthetic and natural antioxidants in stabilizing biodiesel. The study evaluated synthetic antioxidants, specifically hydrogenated methoxy eugenol, and natural antioxidants derived from the methanolic extract of wild loquat plants, along with a comparison to commonly used synthetic antioxidants. Comprehensive simulations and modeling were conducted using Aspen Plus® V10 commercial simulation software in a block‐wise manner. The technical performance was assessed by considering the quantities and qualities of biodiesel, glycerol, and antioxidants. The synthetic antioxidant processes resulted in negative net present values and longer payback periods of 11.7 to 17.8 years, while natural antioxidants showed shorter payback periods ranging from 3.8 to 12 years. Natural antioxidants, particularly those extracted from clove wastes and wild loquat plant parts, demonstrated superior techno‐economic performance with the lowest operating and raw materials costs, shortest payback period, highest internal rate of return (IRR), and best profitability. Therefore, natural antioxidants are the most economically viable option for biodiesel stabilization, outperforming synthetic antioxidants in terms of operating costs, payback period, IRR, and profitability.

Deamination mechanism of modified magnesium slag using wet aging and its performance evolution as backfill material.

The purpose of this study is to solve the problem of ammonia (NH3) release when modified magnesium slag (MMS) is used as coal mine backfill cementitious material, and to explore its chemical mechanism and put forward effective solutions. Uniaxial compressive strengths (UCS) hydration kinetics, scanning electron microscope (SEM), and thermogravimetric analysis-derivative thermogravimetry (TG-DTG), X-ray diffractometer (XRD) and other testing methods were used to study the evolution of the properties of MMS-based backfill material, which provided a scientific basis for the safe utilization of MMS. First, the chemical mechanism underlying the release of NH3 from MMS was identified, and it was confirmed that Mg3N2 and Li3N are the main nitrogen sources. This conclusion is based on thermochemical theory and the Pidgeon method. Secondly, the wet aging method was proposed to reduce the NH3 release from MMS-based backfill material. In addition, a continuous on-line gas detection system was used to determine the NH3 release pattern of MMS-based cementitious material under various aging water contents. The experiment showed a significant reduction in NH3 release with a lower aging water content of 3% and a reduction ratio as high as 81.55%. As the aging water content increased, the 28-day UCS gradually decreased. However, compared to the dry aging group, it remained above 3MPa when the aging water content was below 6%. The wet aging method can significantly shorten the pre-induction, induction, and acceleration periods of MMS-based cementitious material. The microstructure of the wet aging group exhibited fewer needle-like and rod-like ettringite (AFt) crystals as well as less flocculent hydrated calcium silicate (C-S-H) gel, whereas the unhydrated group had more fly ash (FA) and pores. Considering the UCS and NH3 release performance of MMS-based cementitious material, it is recommended to adopt a 3% aging water content and control the aging period to 7 days to effectively reduce NH3 release while ensuring the material's strength, thereby meeting the application requirements for coal mine backfill cementitious material.

P0691 Impact of Ozanimod (OZA) on Circulating Neutrophils: Results from the Phase 3 Japanese True North (J-TN) Study of Patients (Pts) With Moderately to Severely Active Ulcerative Colitis (UC)

Abstract Background OZA was approved for treatment (tx) of moderately to severely active UC in adults based on TN study results. Increases in circulating neutrophils are an indicator of systemic inflammation, and increased infiltration of activated neutrophils in intestinal mucosa contributes to mucosal inflammation in inflammatory bowel disease (IBD). Human neutrophil elastase-mediated degradation of calprotectin (CPa9-HNE) is a measure of neutrophil activity. Methods The effect of OZA on neutrophils and CPa9-HNE levels and the association of neutrophils and CPa9-HNE levels with OZA efficacy were assessed in all J-TN pts. During the 12-wk induction period, pts were randomized to OZA 0.46 mg, OZA 0.92 mg or placebo (PBO). OZA clinical responders at Week (W) 12 were continually assigned treatment to OZA or PBO for maintenance through W52. Circulating neutrophil and CPa9-HNE levels were analyzed at baseline and throughout the induction periods. Neutrophil and CPa9-HNE levels were explored by clinical response status at W12 and W52. Results Absolute neutrophil counts remained within the normal range throughout the induction and maintenance periods. Circulating neutrophil levels decreased with OZA 0.46 mg and 0.92 mg during induction and were significantly lower than those observed with PBO. Neutrophil levels significantly decreased by 2 weeks of treatment with OZA at 0.92mg dose groups compared to baseline. Circulating neutrophils remained low with continued OZA during induction period. Decreases in circulating neutrophil levels were greater in patients with clinical response starting at Week 9 (responders) than those without clinical response at Week 12 (nonresponders) in both dose Oza-treated pts groups during the induction period. CPa9-HNE levels also decreased with OZA 0.92 mg during induction period as compared with PBO and baseline. However, No significant difference of circulating Cpa9-HNE levels between responder vs nonresponser with Oza treatment at week 12. Baseline NEUT was positively associated with baseline stool frequency, 9-point Mayo and CRP. Baseline Cpa9-HNE levels was positively associate with baseline CRP. Furthermore, CfB NEUT was positively associated with CfB Physician Global Assessment, Rectal Bleeding and CRP with Oza 0.92mg treatment at week 12. CfB NEUT and Cpa9-HNE was positively associated with CfB CRP with both dose Oza treatments at week 12. Conclusion Circulating inflammatory markers of neutrophils and CPa9-HNE decreased with ozanimod use. These findings support the use of circulating neutrophils and CPa9-HNE, a measure of neutrophil activity, as pharmacodynamic markers for ozanimod treatment effect and potential disease markers in patients with UC.

P0669 Safety of intravenous and subcutaneous guselkumab induction administration: Results from the GALAXI and GRAVITI studies in participants with Crohn’s Disease

Abstract Background Guselkumab (GUS) is a dual-acting IL-23 inhibitor that potently neutralizes IL-23 and binds to CD64, a receptor on cells that produce IL-23. Induction with both intravenous (IV) and subcutaneous (SC) GUS was effective in phase 2/3 clinical trials of participants (pts) with moderately to severely active Crohn’s disease (CD). To characterize the safety of GUS IV and SC induction regimens, we evaluated safety data from clinical trials of GUS in CD. Methods We evaluated data from phase 2/3 CD studies with IV induction (GUS 200mg IV q4w in GALAXI 1, 2, and 3) and SC induction (GUS 400mg SCq4w in GRAVITI) to assess rates of safety events (proportions of pts with ≥1 event) during the induction period (Week 0-12). Results During the induction period, rates were not higher in either the IV or the SC groups than the respective placebo (PBO) groups for adverse events (AEs), serious AEs, or AEs leading to discontinuation (Table 1). Serious infections occurred in 1 pt in the GUS IV group and 1 pt in the GUS SC group; neither led to discontinuation of study treatment. No serious infections were reported in PBO-treated pts in either group. Of the 1376 GUS SC injections during the induction period in GRAVITI, 6 (0.4%) were associated with injection site reactions, which included pruritus, erythema, and swelling. Injection site reactions beyond the induction period with GUS SC in GALAXI and GRAVITI remained low (≤1%) and were comparable regardless of induction administration route. No cases of active tuberculosis, anaphylaxis, serum sickness reactions, major adverse cardiovascular events, or venous thromboembolism were reported during the induction period. In the IV induction group, 1 opportunistic infection (esophageal candidiasis) was reported in a PBO-treated pt and 2 were reported in GUS-treated pts (cytomegalovirus infection and esophageal candidiasis). In the SC induction group, 1 opportunistic infection of esophageal candidiasis was reported in a PBO-treated pt and 0 were reported in GUS-treated pts. One malignancy (basal cell carcinoma) not leading to discontinuation was reported in a pt in the GUS 400 mg SC group. One death was attributed to a non-suicidal (not self-inflicted) gunshot wound in a pt treated with GUS SC. Clinically significant hepatic disorders were reported in 2 pts in the GUS 200mg IV group (1 SAE and 1 AE that led to discontinuation) and 1 pt in the GUS 400mg SC group (1 AE that led to discontinuation) during the induction period. All cases were confounded by additional diagnoses or concomitant medications. Conclusion Both IV and SC induction demonstrated comparable safety results consistent with the well-characterized GUS safety profile. No new safety concerns were identified.

DOP052 Etrasimod as induction and maintenance therapy in Asian patients with moderately to severely active Ulcerative Colitis: Results from the maintenance period of a randomised, double-blind, placebo-controlled, multi-centre Phase 3 study (ES101002)

Abstract Background Etrasimod (ETR) is an oral, once daily (qd), selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). ES101002 was a registrational Phase (Ph) 3 study evaluating the efficacy and safety of ETR in Asian patients (pts) with moderately to severely active UC (NCT04176588). ETR has shown significant benefit vs placebo (PBO) as induction and maintenance therapy in pts with UC, including in the 12-week (wk) induction period (IP) of ES101002.1–4 Here, we report results from the 40-wk maintenance period (MP) of ES101002. Methods The study comprised a 12-wk IP, 40-wk MP, and open-label (OL) period (up to 40 wks). Eligible pts were enrolled from the Chinese mainland, Taiwan, and South Korea, had confirmed moderately to severely active UC, and had failed ≥1 UC treatment (conventional and/or biologics/JAK inhibitors). Pts randomised 2:1 into the IP received ETR 2 mg qd or PBO for 12 wks. Clinical responders at wk 12 were re-randomised 1:1 into the MP and received ETR or PBO for 40 wks. In the MP, stratification factors were treatment in the IP, previous exposure to biologics/JAK inhibitors, and concomitant use of corticosteroids at IP baseline. IP non-responders or pts who experienced UC worsening in IP/MP were offered entrance into the OL period. The objectives for the MP of the study were to evaluate the efficacy and safety of ETR vs PBO. Results A total of 158 pts were randomised into the MP and received treatment (77 ETR; 81 PBO). Baseline pt demographics and disease characteristics, including mean age (43.8 years [yrs] ETR; 40.7 yrs PBO), proportion of female pts (45.5% ETR; 40.0% PBO), and mean baseline modified Mayo Score (6.0 ETR; 5.8 PBO), were balanced between groups. A higher proportion of pts receiving ETR (89.6%) vs PBO (51.9%) completed the 40-wk MP. All efficacy objectives in the 40-wk MP were achieved (Figure 1). A significantly greater proportion of pts receiving ETR vs PBO achieved clinical remission, clinical response, endoscopic improvement, endoscopic normalisation, mucosal healing, and symptomatic remission (P<.0001 each). Most treatment-emergent adverse events (TEAEs) were mild to moderate in severity (Table 1). ETR vs PBO resulted in fewer Grade 3 TEAEs (ETR 10.4%, PBO 13.6%) and serious adverse events (ETR 7.8%, PBO 8.6%). In each group, there was a single treatment discontinuation due to a TEAE (UC worsening) with no Grade 4 TEAEs or deaths. Conclusion Consistent with previous studies, ETR resulted in clinically meaningful and statistically significant improvement of UC in Asian pts across clinical, endoscopic, and histologic endpoints, and was safe and well-tolerated.

P0749 Infection adverse events with tulisokibart over 50 weeks of treatment in the phase 2 Crohn’s disease APOLLO-CD trial

Abstract Background Biologic medications for inflammatory bowel disease are associated with increased risk of infections1. This analysis evaluates infection adverse events (AEs) with tulisokibart, an anti-tumor necrosis factor–like cytokine 1A (TL1A) monoclonal antibody, in APOLLO-CD, a Phase 2a trial in participants with Crohn’s disease (CD) in which tulisokibart was well tolerated and led to achievement of endoscopic response and other endpoints during a 12-week induction period and 36-week open-label extension (OLE) period2 Methods Participants (≥18 years of age, moderately to severely active CD and inadequate response to conventional therapy or approved biologic therapies) received open label intravenous (IV) induction tulisokibart treatment (1000 mg at baseline then 500 mg at Weeks 2, 6, and 10). Tulisokibart induction responders were able to enter the OLE study and randomized at week 14 to receive IV tulisokibart 100 mg or 250 mg every 4 weeks. Adverse events (AEs) related to infections during the 12-week induction and up to Week 50 in the OLE are reported. Results A total of 55 participants were treated in the induction period, of which 37 responders continued in the OLE (19 received tulisokibart 100 mg and 18 received tulisokibart 250 mg). During the induction period, 25 (46%) participants reported infection AEs; all were considered mild to moderate in severity, and the most common were COVID-19 and Urinary Tract Infection (Table). Two infections were serious (anal abscess and COVID-19 pneumonia), requiring hospitalization; both were deemed not drug related and resolved without treatment discontinuation. In the OLE at Week 50, 12 (63%) participants on 100 mg and 11 (61%) on 250 mg reported infection AEs, with none considered serious. The most common infection AEs were Urinary Tract Infection and COVID-19. There were two severe infection AEs (bronchitis and Clostridioides difficile) in the 250 mg dose group. No participants discontinued study treatment due to an infection AE during the entire 50 weeks of treatment (Table). No dose-dependent safety signal was observed. Conclusion Tulisokibart treatment over the 12-week induction demonstrated low incidence of serious infection AEs and no apparent increased risk of infection AEs when compared with biologic treatments for CD in prior clinical trials3,4. No new infection safety signals appeared in the OLE. All infection AEs resolved, most were considered non-serious and mild to moderate in severity, and no participant discontinued treatment due to an infection AE.

DOP092 Efficacy and safety of a second JAK inhibitor in Ulcerative Colitis : J2J multicenter cohort

Abstract Background Very few data exist on the use of a second JAK inhibitor (JAKi) in patients with ulcerative colitis (UC), already exposed to a first line of JAKi. The aim of this study was to evaluate the efficacy and safety of a second line of JAKi in UC. Methods We conducted an ambispective observational multicenter study in 28 Belgian and French centers. All patients with refractory UC, previously exposed to a first-line JAKi and subsequently receiving another JAKi, were included between July 2019 and September 2024. The primary endpoint was corticosteroid-free clinical remission at the end of the induction period (weeks 8-14), defined by a partial Mayo score ≤ 2 without any subscore > 1. Results A total of 153 patients, 61% men, with a median age at diagnosis of 23 years (IQR [18.1-34.7]), were included and followed up for a median of 3 months (IQR [2- 10.9]). The median duration of disease was 7 years (IQR [4.2- 11.9]) and 90% of patients had been exposed to at least two biologics (excluding JAKi). The first-line JAKi was tofacitinib for 107 patients (70%), filgotinib for 38 (25%) and upadacitinib for 8 patients (5%). At baseline, the median partial mayo score was 6 (IQR [5-8]), the median CRP was 4.6 mg/L (IQR [1.5-14]) and the median fecal calprotectin was 611 μg/g (IQR [325-1488]). In second-line treatment, 96 patients (63%) received upadacitinib, 48 (31%) filgotinib and 9 (6%) tofacitinib. Follow-up data for the induction period were available for 125 patients. At week 8-14, 57/125 patients (46%) were in corticosteroid-free remission, including 40/78 on upadacitinib (51%), 15/40 (38%) on filgotinib and 2/7 (29%) on tofacitinib. No significant difference was found in steroid-free remission rates between upadacitinib and filgotinib at induction (p=0.19). Clinical response was achieved in 57 patients (73%) on upadacitinib, 23 patients (58%) on filgotinib and 5 patients (71%) on tofacitinib. The median partial Mayo score, CRP and calprotectin were 2 (IQR [0 ;3]), 1 (IQR [1 ;6.7]) and 385 μg/g (IQR [90 ;855]) respectively, for the overall population. Among the 23 patients (18%) who discontinued treatment before weeks 8-14, the reason was primary failure for 16 patients (70%) and an adverse event for 6 (26%). During the induction period, 14 patients (18%) on upadacitinib experienced AEs, the most frequent being acne; 8 (19%) on filgotinib; and 2 (29%) on tofacitinib. No cases of herpes zoster, cancer or vascular accident were observed. Seven (5%) patients underwent colectomy during follow-up. Conclusion In refractory UC, 46% of patients treated with a second JAKi were in corticosteroid-free remission at the end of the induction phase, with no significant difference based on the molecule used.

P0931 Induction treatment with upadacitinib is associated with high rate of clinical response in patients with refractory Inflammatory Bowel Disease

Abstract Background Upadacitinib is an oral selective Janus kinase-1 (JAK1) inhibitor, that has been approved for the treatment of moderate to severe Ulcerative Colitis (UC) and Crohn’s Disease (CD). The recommended induction dose is 45 mg once daily for 8 weeks for UC and 12 weeks for CD, followed, thereafter, by a maintenance dose of 15 mg or 30mg (for patients with refractory, severe or extensive disease). Our study aims to capture the experience of two tertiary centers on upadacitinib use in refractory UC and CD. Methods This is an ongoing, prospective cohort study. Demographic and disease-related data were collected at baseline. Our primary endpoint is clinical response (CR) at the end of induction, defined as >50% decrease in Patient Reported Outcomes (PROs) and secondary endpoints were steroid-free clinical remission (sf-CRem) and treatment persistence. SPSS23 was used for the statistical analysis. Results The baseline characteristics of our patients are presented in Table 1. At drug initiation, 35.4% were receiving concomitant corticosteroids. The induction period has been concluded by 23/26 patients with UC and 17/21 patients with CD, of whom 22 (95.7%) and 13 (76.5%) respectively commenced maintenance treatment. The primary endpoint of CR was achieved by 19 out of 20 (95%) patients with clinically active UC and 11 out of 16 (68.8%) patients with clinically active CD at baseline. Sf-CRem was achieved by 21/23 (91.3%) patients with UC and 13/17 (76.5%) with CD. The majority of patients with either UC (86.4%) or CD (84.6%) commenced maintenance therapy with a 30 mg dose. Adverse events occurred in 22.9% of patients in our cohort, with acne being the most frequently reported (12.5%). One patient (2.1%) experienced herpes simplex infection and two (4.2%) an increase in their lipid levels, requiring initiation of antihyperlipidemic therapy. No serious adverse events have been reported. Conclusion In our cohort of patients with Inflammatory Bowel Disease who were refractory to multiple advanced treatments, upadacitinib has been shown to be an effective and safe therapeutic option for induction of remission. Most patients with medically refractory IBD in our cohort have received increased maintenance Upadacitinib dosage.

P0633 Real World Outcomes of Upadacitinib Induction Therapy for Patient with Inflammatory Bowel Disease in Korea

Abstract Background Upadacitnib (UPA) has demonstrated efficacy and safety in both patients with Crohn’s disease (CD) and ulcerative colitis (UC) in pivotal clinical trials.1,2 Still, there is a lack of data on real-world effectiveness and safety of UPA for Asian patients with IBD. Methods We retrospectively analysed data of patients with IBD who received UPA induction therapy. Clinical effectiveness (excluding those in clinical remission at baseline), endoscopic outcomes (UC), biochemical outcomes and safety were evaluated (at week 12 in CD and at week 16 in UC). Clinical remission was defined as follows: clinical response together with Crohn’s disease activity index [CDAI] <150) (CD) and partial Mayo score ≤2 with combined rectal bleeding [RB] score and stool frequency score ≤1 (UC). Definitions for clinical response were a reduction of the CDAI score ≥100 from baseline in CD and a reduction of partial Mayo score ≥3 together with at least 30% from baseline and decrease in RB score ≥1 or absolute RB score ≤1 in UC. Endoscopic remission was defined as Mayo Endoscopic subscore [MES] =0 or Ulcerative Colitis Endoscopic Index of Severity [UCEIS] =0 and endoscopic response as a reduction of MES ≥1 or reduction of UCEIS ≥2. Results From September 2023 to October 2024, a total of 89 patients with IBD initiated UPA induction therapy. Among those patients, 53 patients (39 with CD and 14 with UC) completed induction therapy, while one patient with UC discontinued UPA three weeks after initiation of UPA due to worsening symptoms of UC. Median disease duration was 10 years, and 27 (50.0%) had been exposed to more than one advanced therapy. Of the CD patients, 27 (68.2%) exhibited either stricturing or penetrating behaviour. Among UC patients, 9 (60.0%) had extensive disease (Table 1). In patients with CD, clinical remission and clinical response were observed in 8/23 (34.8%) and 10/23 (43.5%), respectively. In patients with UC, clinical remission and clinical response were observed in 9/13 (69.2%) and in 9/13 (69.2%), respectively. Endoscopic remission and endoscopic response were observed in 5/15 (33.3%) and 10/14 (71.4%), respectively. In both CD and UC patients, disease activity scores and biomarker levels showed decreasing trends throughout the induction period (Figure 1). During the induction therapy, acne was reported in 12/54 patients (22.2%), without any other significant adverse events such as Herpes zoster, deep vein thrombosis, and major adverse cardiovascular events. Conclusion UPA induction therapy was effective for Korean patients with refractory IBD with an acceptable safety profile. Financial support This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2021R1A2C2095096).

P0609 Real-world short and long-term effectiveness of risankizumab in refractory Crohn’s disease: RISANCROHN study from the ENEIDA Registry

Abstract Background Phase III trials have demonstrated the efficacy of risankizumab (RZB), this being the first humanized monoclonal IgG1 antibody which targets the interleukin 23 p19 subunit, in Crohn’s disease (CD). However, real-world data with this drug is limited. The aim of our study was to assess the real-world effectiveness of RZB in patients with CD. Methods Adult CD patients that had received treatment with RZB in the ENEIDA registry —a large prospectively maintained Spanish database promoted by the Spanish Working Group of Crohn’s and Colitis (GETECCU)— were included. Clinical and demographical data including number of previous biologics and advanced therapies were included. The primary endpoints were steroid-free clinical remission (SFCR) after induction period (Harvey-Bradshaw score <5) and long-term SFCR at the end of follow-up. Influence of previous use of ustekinumab (UST) and number of previous advanced therapies in short- and long-term efficacy was also evaluated. Statistical analysis was performed using the Chi-square/Student-t test and multivariate analysis with logistic regression. Results 857 CD patients (60% male) were included: median age 50 (18-84) years, median disease duration 14 years, 27% smokers. 50% were L1, 8% L2, 38% L3, and 4% exclusively L4. B1 phenotype was present in 42%, 37% B2, 21% B3. Perianal disease was present in 28%, 46% had previously CD-related surgery and 39% extraintestinal manifestations. Only 3% were biological naïve, 50% had been exposed to 1-2 advanced therapies, and 47% to 3 or more. Following induction 56% of the patients achieved SFCR. Remission was more frequent in patients who had not previously been treated with UST (64% vs. 53% in those previously exposed to UST, p<0.01). In the multivariate analysis, a higher number of prior advanced therapies was associated with lower remission rates (p<0.01). Long-term efficacy was evaluated in 652 patients (median follow-up 7 months). At the end of the follow-up 61.2% of patients maintained SFCR. Long-term remission rate in patients non-exposed to UST was 72%, and 55% exposed to UST (p<0.01). In the multivariate analysis, younger age was associated with higher long-term remission rates (p<0.01). 11% needed dose optimization/reinduction during follow-up. 68 patients (7.9%) presented adverse events but only 18 (2%) needed to give up the treatment. Conclusion This study represents the largest cohort of real-world data on RZB in CD, including highly refractory patients with multiple prior drug failures. RZB induced SFCR in 56% of patients after induction and 61% in the long term. Higher remission rates were observed in patients who had never been exposed to UST. Younger age and fewer previous advanced therapies were associated with better outcomes.

P0847 Comparative efficacy on steroid-free remission of pharmacological therapies for moderate-to-severe Ulcerative Colitis: A systematic review and network meta-analysis

Abstract Background We performed a systematic review and network meta-analysis to assess the comparative efficacy of pharmacological therapies in achieving steroid-free remission for patients with moderate-to-severe ulcerative colitis (UC). Methods We conducted a comprehensive search of electronic databases and grey literature up to September 2024 to identify randomized controlled trials in adults with moderate-to-severe UC, comparing advanced therapies. The primary endpoint was corticosteroid-free clinical remission at the end of maintenance therapy. We combined direct and indirect evidence through multivariate random-effects network meta-analyses, and the relative ranking of treatments was assessed using surface under the cumulative ranking (SUCRA) probabilities. Additionally, subgroup analyses were performed based on prior anti-TNF exposure. Confidence in the estimates was evaluated using the CINeMA (Confidence in Network Meta-Analysis) framework. Results We included 22 studies (5 infliximab, 2 adalimumab, 2 golimumab, 3 vedolizumab, 1 ustekinumab, 1 ozanimod, 2 filgotinib, 1 upadacitinib, 1 etrasimod, 1 mirikizumab, 1 tofacitinib, 1 risankizumab, 1 guselkumab). Randomized controlled trials were categorized into two study designs: re-randomization of patients after an induction period and treat-through patients. All interventions except golimumab and filgotinib 100mg were superior to placebo for steroid-free remission in re-randomized patients (Figure 1). In re-randomized anti-TNF-naive patients, no agents were superior to placebo, while in anti-TNF-experienced patients, upadacitinib, risankizumab, and mirikizumab had significantly higher remission rates than placebo. In treat-through patients, all interventions except vedolizumab were superior to placebo for steroid-free remission (Figure 2). Etrasimod achieved significantly higher remission rates than placebo in treat-through anti-TNF-experienced patients, while etrasimod and infliximab achieved significantly higher rates in re-randomized anti-TNF-naive patients. Regarding efficacy, upadacitinib 30 mg/day ranked first for re-randomized patients (SUCRA 94.4%), while etrasimod 2 mg/day ranked first for treat-through patients (SUCRA 91%). Our confidence in estimates was very low due to imprecision and high risk of bias in included studies. Conclusion Very low-quality evidence supports the efficacy of all interventions except golimumab, vedolizumab, and filgotinib 100mg for steroid-free remission. Upadacitinib 30 mg/day and etrasimod 2 mg/day were ranked highest for efficacy in re-randomized and treat-through patients, respectively.

P0382 Identifying atypical disease phenotypes in paediatric Ulcerative Colitis: Insights from the real world PIBD-SETQuality cohort

Abstract Background The heterogeneity of paediatric ulcerative colitis (P-UC) can complicate diagnosis and prompt start of optimal induction treatment, which is crucial for adequate disease control. Recognizing and understanding atypical disease patterns in P-UC will decrease misclassification and contribute to the development of standardized classification tools. This study aims to provide insight in the real world prevalence of atypical phenotypes in newly diagnosed P-UC patients. Methods Data were collected from the Paediatric Inflammatory Bowel Diseases Network for Safety, Efficacy, Treatment and Quality improvement of care (PIBD-SETQuality) cohort, a multicenter, international, prospective, observational study including therapy naive children <19 years old with IBD. Patients diagnosed with UC between January 1st 2017 and June 14th 2024 were enrolled. Diagnostic criteria and macroscopical atypical disease were based on the validated PIBD-classes algorithm by revised Porto Criteria1. The Mann-Whitney U test and Chi-square tests were used to compare, respectively, numerical and categorical data between patient groups. Results Baseline data of 197 P-UC patients were included. At diagnosis, 68% of the patients presented with pancolitis. Atypical disease occurred in 35.0% (69/197) of the patients of which relative rectal sparing was most common (Table 1). Aspecific upper gastrointestinal inflammation occurred in 10.6% (17/161) of the patients, of whom 6 also exhibited atypical disease phenotypes. Approximately 1 out of 10 patients with atypical disease presented with multiple atypical phenotypes. Patients with atypical disease did not show significant differences compared to patients without atypical disease in time to diagnosis (107 days vs. 104 days, P=0.19), absolute PUCAI score (40 [IQR 30-55] vs. 35 [IQR 25-58.75], p=0.10), initial induction therapy and need for treatment intensification during induction therapy (8 vs. 4 patients, p=0.22). Conclusion Atypical disease presentations are common in P-UC in this real world cohort, as is the presence of combined atypical disease features. Recognition of atypical disease features in P-UC, and understanding their impact on disease course, are crucial for prompt start of optimal tailored therapy. In this cohort, the presence of atypical disease did not result in a diagnostic delay or treatment intensification during induction period.

P1042 Effectiveness and safety of vedolizumab in real-world studies in Chinese patients with inflammatory bowel disease: a systematic review and meta-analysis

Abstract Background Inflammatory bowel diseases (IBD), consisting of Crohn’s disease (CD) and ulcerative colitis (UC), are chronic gastrointestinal conditions with increasing prevalence in China. Vedolizumab (VDZ), a humanized monoclonal antibody that targets α4β7 integrin, has been approved for use in China since 2020. This systematic review and meta-analysis aimed to evaluate the real-world effectiveness and safety of VDZ in Chinese patients with IBD. Methods A systematic literature search was conducted on 20th Dec 2023 to identify real-world studies evaluating intravenous VDZ in Chinese patients with IBD. Meta-analyses were performed separately for CD and UC patients using a random-effects model in R software to pool clinical remission and response rates, and endoscopic remission rates across induction (6-14 weeks), medium term (22-30 weeks), and long term (over 48 or 52 weeks). Subgroup analysis was conducted based on the history of biologics. Incidence of adverse events (AE), serious AE (SAE), and serious infection was assessed for safety. Results A total of 20 studies (12 CD, and 15 UC), involving 1472 patients (610 CD, and 862 UC), were included in the analysis (Figure 1). During the induction phase, a clinical response and clinical remission were achieved by 71.31% and 75.58% of CD patients, and 67.89% and 46.46% of UC patients, respectively. In the medium term, 64.32% of CD patients and 65.72% of UC patients achieved a clinical response, while 60.72% of CD patients and 60.95% of UC patients achieved clinical remission. In the long term, clinical response rates were 57.14% in CD patients and 73.50% in UC patients, while clinical remission rates were 51.28% and 60.84% for CD and UC patients, respectively. For the endoscopic remission, there were 11.11%, 18.41%, and 36.42% of that in CD patients, and 44.58%, 53.32%, and 62.40% of that in UC patients were achieved in the induction, medium term, and long term. Subgroup analyses indicated that both bio-naïve and bio-exposed patients, in both UC and CD groups, showed relatively favourable outcomes across the available time points (Table 1). Adverse events (AEs) were reported in 6.67% to 61.54% of CD patients, and 29.69% to 75.38% of UC patients. Serious adverse events (SAEs) and serious infection rates ranged from 0.00% to 1.56%, and 0.00% to 2.70%, respectively, in UC patients, while neither SAE nor serious infections were reported in the CD studies. Conclusion VDZ demonstrated favourable effectiveness in Chinese patients with IBD across induction, medium- and long-term treatment periods, with a good safety profile.

P0813 Integrated summary of safety of obefazimod for patients with moderately to severely active ulcerative colitis

Abstract Background Obefazimod is an oral, once-daily (QD), small molecule which enhances expression of microRNA-124 and is currently in phase 3 clinical trials for the treatment of patients with moderately to severely active ulcerative colitis (UC) [1]. Obefazimod demonstrated efficacy and safety in patients with UC across 4 clinical studies: two placebo-controlled Phase 2 induction trials, and two subsequent open-label maintenance (OLM) studies [2, 3]. Here we report an integrated safety analysis of those studies in the UC clinical program. Methods Exposure-adjusted incidence rates (EAIRs per patients-years [PY]) of treatment emergent adverse events (TEAEs) were examined among patients from the induction trials (NCT03093259, NCT03760003), and the OLM studies (NCT03368118, NCT04023396). Patients received one of three obefazimod doses (25mg, 50mg or 100mg QD) or placebo during induction, and all patients received 50 mg QD during OLM studies. Results Demographics and disease characteristics were similar among treatment groups. Exposure for all obefazimod-treated patients (N=274) was 440.1 PY including induction and maintenance periods. EAIR of TEAEs per PY was 1.40 in obefazimod-treated patients and 2.40 in placebo-treated patients (N=73), with TEAEs occurring in 78.5% and 47.9% of patients, respectively (Table 1). The most common TEAEs (EAIR per PY ≥ 0.05) in all obefazimod-treated patients included headache, Covid-19, ulcerative colitis, nasopharyngitis, and nausea. For each of these TEAEs, the incidence per PY was numerically lower in the group of all obefazimod-treated patients relative to placebo. Conclusion This integrated safety analysis of the 4 completed studies in the obefazimod UC clinical program indicates that exposure-adjusted incidence rates of TEAEs were generally numerically lower among patients treated with obefazimod relative to placebo. Integrated safety data further support a favorable safety and tolerability profile.