Corticosteroid-free Remission Research Articles

Effectiveness and Safety of Ustekinumab in Pediatric Ulcerative Colitis: A Multi-center Retrospective Study from the Pediatric IBD Porto Group of ESPGHAN.

Current data on ustekinumab therapy in children with ulcerative colitis (UC) or unclassified inflammatory bowel disease (IBDU) are limited. We aimed to evaluate the effectiveness and safety of ustekinumab in pediatric UC and IBDU. This multicenter retrospective study included 16 centers affiliated with the IBD Interest and Porto groups of ESPGHAN. Children with UC or IBDU treated with ustekinumab were enrolled. Demographic, clinical, laboratory, endoscopic, and imaging data as well as adverse events were recorded. Analyses were all based on the intention-to-treat principle. Fifty-eight children (39 UC and 19 IBDU, median age 14.5 [IQR 11.5-16.5] years) were included. All had failed biologic therapies, and 38 (66%) had failed two or more biologics. Corticosteroid-free clinical remission (CFR) was observed in 27 (47%), 33 (57%), and 37 (64%) children at 16, 26, and 52 weeks, respectively. Normalization of C-reactive protein and calprotectin <150μg/g were achieved in 60% and 52%, respectively, by 52 weeks. Endoscopic and radiologic remissions were reached in 8% and 23%, respectively. The main predictors of CFR were diagnosis of UC compared with IBDU (hazard ratio [HR] 2.2, 95% CI 1.03-4.85; p=0.041) and no prior vedolizumab therapy (HR 2.1, 95% CI 1.11-4.27; p=0.023). Ustekinumab serum levels were not associated with disease activity. Adverse events were recorded in six (10%) children, leading to discontinuation of the drug in three. Based on these findings, ustekinumab appears as an effective therapy for pediatric refractory UC and IBDU. The potential efficacy should be weighed against the risks of serious adverse events.

Resolution of rectal bleeding by day 7 in acute severe ulcerative colitis is prognostic for post-discharge corticosteroid free clinical remission and endoscopic improvement.

This study assesses two different disease activity measures, the MTWSI and the partial Mayo score, in hospitalized acute severe UC patients for prediction of post-discharge corticosteroid-free clinical remission and endoscopic improvement to help guide future considerations for disease activity assessment. In this post-hoc analysis from the TRIUMPH trial, these results suggest resolution of Mayo rectal bleeding sub-score may have high prognostic utility and could be considered as a primary endpoint for hospitalized UC trials. The study underscores the need for further research on patient-reported outcomes and endoscopic indices in larger populations for inpatient UC trials.

Granulocyte and monocyte adsorptive apheresis (GMA) in patients with inflammatory bowel disease: A useful therapeutic tool not just in ulcerative colitis but also in Crohn's disease

IntroductionGranulocyte and monocyte adsorptive apheresis (GMA) removes neutrophils and monocytes from peripheral blood, preventing their incorporation into the inflamed tissue also influencing cytokine balance. Published therapeutic efficacy in ulcerative colitis (UC) is more consistent than in Crohn's disease (CD). We assessed clinical efficacy of GMA in UC and CD 4 weeks after last induction session, at 3 and 12 months, sustained remission and corticosteroid-free remission. Patients and methodRetrospective observational study of UC and CD patients treated with GMA. Partial Disease Activity Index-DAIp in UC and Harvey-Bradshaw Index-HBI in CD assessed efficacy of Adacolumn® with induction and optional maintenance sessions. ResultsWe treated 87 patients (CD-25, UC-62), 87.3% corticosteroid-dependent (CSD), 42.5% refractory/intolerant to immunomodulators. In UC, remission and response were 32.2% and 19.3% after induction, 35.5% and 6.5% at 12 weeks and 29% and 6.5% at 52 weeks. In CD, remission rates were 60%, 52% and 40% respectively. In corticosteroid-dependent and refractory or intolerant to INM patients (UC-41, CD-14), 68.3% of UC achieved remission or response after induction, 51.2% at 12 weeks and 46.3% at 52 weeks, and 62.3%, 64.3% and 42.9% in CD. Maintained remission was achieved by 66.6% in CD and 53.1% in UC. Up to 74.5% of patients required corticosteroids at some timepoint. Corticosteroid-free response/remission was 17.7% in UC and 24% in CD. ConclusionsGMA is a good therapeutic tool for both in UC and CD patients. In corticosteroid-dependent and refractory or intolerant to INM patients it avoids biological therapy or surgery in up to 40% of them in one year.

Effects of prednisolone tapering on effectiveness of infliximab in patients with ulcerative colitis: data from a retrospective cohort

Background and objectiveThe influence of concomitant prednisolone on clinical outcomes and safety in infliximab-treated ulcerative colitis (UC) patients is unknown.Design, setting, participants and outcome measuresA retrospective cohort study was performed,...

Long-term effectiveness and persistence rate of ustekinumab dose intensification in a South East Asian inflammatory bowel disease center.

Ustekinumab (UST) is an effective biologic for treatment of inflammatory bowel disease (IBD). However, some patients treated with UST have suboptimal clinical response with standard dosing. The aims of this study were to determine the effectiveness of UST dose intensification (DI), identify factors associated with DI, cumulative incidence of DI and persistence of UST among treated patients. Clinical data of patients with Crohn's disease (CD) and ulcerative colitis (UC) who received UST from September 2017 to October 2022 in Singapore General Hospital were collected. Primary outcome was defined as achieving corticosteroid-free clinical remission, biochemical remission, endoscopic healing and/or transmural healing (CD). Statistical analysis was performed to identify factors, which are predictive of UST DI and effectiveness of UST DI. Forty-two patients (34 CD and 8 UC) underwent UST DI to either 6-weekly (n=19, 45.2%) or 4-weekly (n=23, 35.9%) and the median time to intensification was 31.1weeks (17.8-65.7). Presence of perianal disease in CD (HR 4.9; 1.47-16.4) was associated with DI. After DI, 16 (38%) patients achieved primary outcome by week 52. The overall drug persistence rates at 1year and 2years were 75.7% (95% CI 62.9-84.6) and 63.5% (95% CI 49.9-74.3), respectively. Two third of IBD patients underwent DI while on UST treatment and the median time to DI was about 6months after induction. CD patients with perianal disease is more likely to undergo DI. More than one third of dose-intensified patients achieved remission by week 52.

Avoidant/restrictive food intake disorder symptoms are not as frequent as other eating disorder symptoms when ulcerative colitis is in remission.

Recent studies have shown that up to 53% of patients with inflammatory bowel disease (IBD) screen positive for avoidant/restrictive food intake disorder (ARFID). There is however concern that ARFID screening rates are over-inflated in patients with active disease. We aimed to evaluate the frequency and characteristics of ARFID symptoms using the Nine Item ARFID Screen (NIAS), and to use another eating disorder measure, the Eating Disorder Examination-Questionnaire 8 (EDE-Q8), to rule-out/characterize other eating disorder cognitive and behavioral symptoms. Participants included adults with UC who are enrolled in an in an ongoing cohort study with quiescent UC (SCCAI ≤2 or fecal calprotectin <150 µg/g with corticosteroid-free clinical remission for ≥ 3 months) at baseline. We used self-reported data on demographics, gastrointestinal medications, medical comorbidities, NIAS scores, and other eating disorder symptom scores (8-item Eating Disorder Examination-Questionnaire; EDE-Q-8). We included 101 participants who completed the NIAS at their baseline cohort assessment (age 49.9±16.5 years; 55% female). Eleven participants (11%) screened positively for ARFID on at least one NIAS subscale (n=8 male). Up to thirty participants (30%) screened positive for other eating disorder symptoms (EDE-Q-8 Global ≥2.3). Overall score distributions on the EDE-Q-8 showed that participants scored highest on the Weight Concern and Shape Concern subscales. Among adults with UC in remission, we found a low rate of ARFID symptoms by the NIAS but a high rate of positive screens for other eating disorder symptoms.

Application of clinical decision support tools for predicting outcomes with vedolizumab therapy in patients with inflammatory bowel disease: A KASID multicentre study.

We aimed to validate clinical decision support tools (CDSTs) to predict real-life effectiveness of vedolizumab (VDZ) in patients with inflammatory bowel disease. We retrospectively enrolled patients with Crohn's disease (CD) or ulcerative colitis (UC) treated with VDZ at 10 tertiary referral centres in Korea between January 2017 and November 2021. We assessed clinical remission (CREM) and response (CRES), corticosteroid-free clinical remission (CSF-CREM) and response (CSF-CRES), biochemical response based on C-reactive protein (BioRES[CRP]) and faecal calprotectin (BioRES[FC]), endoscopic healing (EH), and the need to optimise or switch drugs based on CDST-defined response groups. Additionally, the area under the receiver operating characteristics curve (AUC) for the CDSTs was calculated. We included 143 patients with CD and 219 with UC. We observed incremental trends on CSF-CRES at week 14 (W14) (ptrend = 0.004) and decreasing trends for the need to optimise or switch drugs (ptrend = 0.016) in CD from the low to high probability groups. Except for CSF-CREM at W54, we noticed incremental trends for all clinical responses at W14, W26 and W54 (ptrend <0.001) in UC. W26 and W54 BioRES[CRP] and W14 EH also showed increasing trends (ptrend <0.05) in UC. With increasing probabilities of response, drug optimisation or switching was less frequently required in UC (ptrend = 0.013). With 26 points cut-off, CDSTs effectively identified W14 CSF-CRES, W26 BioRES[CRP], BioRES[FC] and W54 BioRES[CRP] in UC, all with AUCs >0.600, whereas CDSTs showed poor accuracy in CD. CDSTs for VDZ had acceptable accuracy in predicting effectiveness outcomes including clinical and biochemical outcomes in UC. However, their utility in CD was limited.

Real-world effectiveness of upadacitinib in Crohn’s disease: a UK multicentre retrospective cohort study

BackgroundUpadacitinib is a Janus kinase inhibitor, which has recently been approved for treating Crohn’s disease. There are limited real-world studies on the outcomes of upadacitinib in Crohn’s disease.ObjectiveOur aim was...

Efficacy and safety of filgotinib for ulcerative colitis: A real-world multicenter retrospective study in Japan.

While filgotinib, an oral Janus kinase (JAK) 1 preferential inhibitor, is approved for moderately to severely active ulcerative colitis (UC), real-world studies assessing its short- and long-term efficacy and safety are limited. This is a multicenter, retrospective study of UC patients who started filgotinib between March 2022 and September 2023. The primary outcome was clinical remission, defined as a partial Mayo score ≤1 with a rectal bleeding score of 0, or Simple Clinical Colitis Activity Index (SCCAI) ≤2 with a blood-in-stool score of 0. Secondary outcomes included clinical response, corticosteroid-free remission, and endoscopic improvement. Outcomes were assessed at 10, 26, and 58 weeks based on patients with available follow-up. Adverse events were evaluated. We identified 238 UC patients and 54% had prior exposure to biologics/JAK inhibitors. The median baseline partial Mayo score and SCCAI were 5 (IQR 3-6) and 4 (IQR 2-7). Clinical remission rates based on per-protocol analysis at 10, 26, and 58 weeks were 47% (70/149), 55.8% (48/86), and 64.6% (31/48), respectively. At a median follow-up of 28 weeks (IQR 10-54) with a discontinuation rate of 39%, the rates of clinical remission, clinical response, corticosteroid-free remission, and endoscopic improvement were 39.9% (81/203), 54.7% (111/203), and 36.5% (74/203), and 43.5% (10/23), respectively. These rates were comparable between biologic/JAK inhibitor-naïve and -experienced patients. While three patients (1.3%) developed herpes zoster infection, no cases of thrombosis or death were reported. Real-world data demonstrate favourable clinical and safety outcomes of filgotinib for UC.

Real-world effectiveness of ustekinumab and vedolizumab in TNF-exposed pediatric patients with ulcerative colitis.

Vedolizumab (VDZ) and ustekinumab (UST) are second-line treatments in pediatric patients with ulcerative colitis (UC) refractory to antitumor necrosis factor (anti-TNF) therapy. Pediatric studies comparing the effectiveness of these medications are lacking. Using a registry from ImproveCareNow (ICN), a global research network in pediatric inflammatory bowel disease, we compared the effectiveness of UST and VDZ in anti-TNF refractory UC. We performed a propensity-score weighted regression analysis to compare corticosteroid-free clinical remission (CFCR) at 6 months from starting second-line therapy. Sensitivity analyses tested the robustness of our findings to different ways of handling missing outcome data. Secondary analyses evaluated alternative proxies of response and infection risk. Our cohort included 262 patients on VDZ and 74 patients on UST. At baseline, the two groups differed on their mean pediatric UC activity index (PUCAI) (p = 0.03) but were otherwise similar. At Month 6, 28.3% of patients on VDZ and 25.8% of those on UST achieved CFCR (p = 0.76). Our primary model showed no difference in CFCR (odds ratio: 0.81; 95% confidence interval [CI]: 0.41-1.59) (p = 0.54). The time to biologic discontinuation was similar in both groups (hazard ratio: 1.26; 95% CI: 0.76-2.08) (p = 0.36), with the reference group being VDZ, and we found no differences in clinical response, growth parameters, hospitalizations, surgeries, infections, or malignancy risk. Sensitivity analyses supported these findings of similar effectiveness. UST and VDZ are similarly effective for inducing clinical remission in anti-TNF refractory UC in pediatric patients. Providers should consider safety, tolerability, cost, and comorbidities when deciding between these therapies.

Precise infliximab exposure and pharmacodynamic control to achieve deep remission in paediatric Crohn’s disease (REMODEL-CD): study protocol for a multicentre, open-label, pragmatic clinical trial in the USA

IntroductionThe only biologic therapy currently approved to treat moderate to severe Crohn’s disease in children (<18 years old) are those that antagonise tumour necrosis factor-alpha (anti-TNF). Therefore, it is critically...

Comparison of endoscopic healing and durability between infliximab originator and CT-P13 in pediatric patients with inflammatory bowel disease.

Favourable clinical data were published on the efficacy of CT-P13, the first biosimilar of infliximab (IFX), in pediatric inflammatory bowel disease (IBD); however, few studies have compared the effect on endoscopic healing (EH) and drug retention rate between the IFX originator and CT-P13. Therefore, we aimed to compare EH and the drug retention rate between the IFX originator and CT-P13. Children with Crohn's disease (CD) and ulcerative colitis (UC)/IBD-unclassified (IBD-U) at 22 medical centers were enrolled, with a retrospective review conducted at 1-year and last follow-up. Clinical remission, EH and drug retention rate were evaluated. We studied 416 pediatric patients with IBD: 77.4% had CD and 22.6% had UC/IBD-U. Among them, 255 (61.3%) received the IFX originator and 161 (38.7%) received CT-P13. No statistically significant differences were found between the IFX originator and CT-P13 in terms of corticosteroid-free remission and adverse events. At 1-year follow-up, EH rates were comparable between them (CD: P=0.902, UC: P=0.860). The estimated cumulative cessation rates were not significantly different between the two groups. In patients with CD, the drug retention rates were 66.1% in the IFX originator and 71.6% in the CT-P13 group at the maximum follow-up period (P >0.05). In patients with UC, the drug retention rates were 49.8% in the IFX originator and 56.3% in the CT-P13 group at the maximum follow-up period (P >0.05). The IFX originator and CT-P13 demonstrated comparable therapeutic response including EH, clinical remission, drug retention rate and safety in pediatric IBD.

Effectiveness of Tofacitinib in Ulcerative Proctitis Compared to Left Sided Colitis and Pancolitis.

Ulcerative proctitis (UP), though associated with high symptom burden and poor quality of life, is excluded from most of the randomized controlled trials in UC, including the OCTAVE trials. We aimed to analyse the effectiveness of tofacitinib in UP, and compare it to that in left sided colitis (LSC) and pancolitis (PC). This was a prospective cohort study. Patients with either steroid-dependent or refractory ulcerative colitis, who received tofacitinib, were divided into three groups based on the disease extent [UP, LSC and PC]. The primary outcome was comparison of proportion of patients in clinical remission in the three groups, at weeks 8, 16 and 48. Safety outcomes were reported using incidence rate per patient year of exposure. Clinical remission was achieved in 47%(15/32), 24%(23/94), and 43%(23/54) of patients at week 8, 56%(18/32), 37%(35/94), and 56%(30/54) of patients at week 16, and 59%(19/32), 38%(36/94), and 24%(13/54) of patients at week 48 in groups UP, LSC and PC, respectively. Corticosteroid-free clinical remission rates were significantly higher in patients in groups UP at week 48. Five (15%) patients with UP were primary non-responders to tofacitinib at week 16, while three (9%) patients had secondary loss of response at week 48. The probability of sustained clinical response was highest in patients with UP. Patients with UP had the lowest incidence of adverse effects. The effectiveness of tofacitinib in inducing and maintaining clinical remission is greater in patients with UP compared to LSC and PC.

A76 COMBINING TOFACITINIB AND USTEKINUMAB FOR REFRACTORY ULCERATIVE COLITIS: A CASE REPORT

Abstract Background The paradigm for Inflammatory Bowel Disease (IBD) management has shifted towards prioritizing remission of inflammation over symptom control, emphasizing sustained, corticosteroid-free remission at the clinical, endoscopic, and histologic levels. The shift is due to the recognition that uncontrolled inflammation often causes morbidity; after one year of biological therapy, 40% of patients still experience persistent disease activity. Several approaches have been proposed to address this challenge, including drug level monitoring, dosage titration, antibody screening, and, as a last resort, surgical intervention. Emerging limited studies suggest the potential efficacy of combining two biological agents or a biological agent with small molecules in IBD, contrasting the efficacy and safety concerns encountered with their use in rheumatological diseases. Aims To describe a case of successful combination therapy with Tofacitinib and Ustekinumab in refractory Ulcerative Colitis with a review of the current literature. Methods This case describes a 35-year-old male patient with severe Ulcerative Colitis refractory to 5-ASA, Azathioprine, Infliximab with Methotrexate, Vedolizumab, Ustekinumab and Tofacitinib. His disease persisted with primary treatment failures requiring hospital admissions and rescuing with parenteral steroids. He was switched back to Ustekinumab with minimal symptom improvement but required repeated steroid courses to achieve control. After deliberations, Tofacitinib was added. This combination achieved remission of his symptoms and inflammatory markers, mainly guided by fecal calprotectin (from 3728 µg/g to 46 µg/g), as well as endoscopic and histologic remission. He is being weaned off the oral budesonide he had been on to augment his response. Results After 4 years of combination therapy, he remains in remission with no adverse events or infections. Reassuringly, Janus Kinase inhibitors (i.e., Tofacitinib) have a short half-life, allowing prompt discontinuation if indicated, especially in the event of infection. Furthermore, biologics such as Vedolizumab, Ustekinumab, and Risankizumab offer minimal systemic immunosuppression and do not appear to raise the risk of infection. Apart from safety concerns and limited data on the use of combination therapy, significant economic implications exist. However, the attainability of cheaper generic forms of small molecules (e.g., Tofacitinib roughly costs a quarter of the brand price in Ontario, Canada) adds another advantage to their combination use. Conclusions Combination therapy with biologics and small molecules is a potential consideration for treating severe or refractory Ulcerative Colitis or IBD. To bridge the knowledge gap regarding combination therapies in IBD, further studies are needed on efficacy, safety, long-term effects, and economic impact. Funding Agencies None

Determining the optimal treatment target in patients with ulcerative colitis: rationale, design, protocol and interim analysis for the randomised controlled VERDICT trial

IntroductionSymptoms, endoscopy and histology have been proposed as therapeutic targets in ulcerative colitis (UC). Observational studies suggest that the achievement of histologic remission may be associated with a lower risk...

Ustekinumab safety and effectiveness in patients with ulcerative colitis: results from a large real-life study

ABSTRACT Background Ustekinumab (UST) is an interleukin-12/interleukin-23 receptor antagonist recently approved for treating ulcerative colitis (UC) but with limited real-world data. Therefore, we evaluated the effectiveness and safety of UST in patients with UC in a real-world setting. Research design and methods This is a multicenter, retrospective, observational cohort study. The primary endpoints were the clinical remission rate (partial Mayo score, PMS, ≤1) and the safety of UST. Other endpoints were corticosteroid-free remission (CSFR) rate, clinical response rate (PMS reduction of at least 2 points), and fecal calprotectin (FC) reduction at week 24. Results We included 256 consecutive patients with UC (M/F 139/117, median age 52). The clinical remission and clinical response rates at eight weeks were 18.7% (44/235) and 53.2% (125/235), respectively, and 27.6% (42/152) and 61.8% (94/152) at 24 weeks, respectively. At 24 weeks, CSFR was 20.3% (31/152), and FC significantly dropped at week 12 (p = 0.0004) and 24 (p = 0.038). At eight weeks, patients naïve or with one previous biologic treatment showed higher remission (p = 0.002) and clinical >response rates (p = 0.018) than patients previously treated with ≥ 2. Adverse events occurred in six patients (2.3%), whereas four patients (1.6%) underwent colectomy. Conclusion This real-world study shows that UST effectively and safely treats patients with UC.

Proactive therapeutic drug monitoring and vedolizumab dose optimization in children with inflammatory bowel disease.

Therapeutic drug monitoring (TDM) and dose optimization have been shown to improve clinical outcomes with antitumor necrosis factor and recent studies in adults suggest an exposure-response relationship with drug levels associated with improved clinical outcomes. However, these levels are not universally recognized as therapeutic targets for vedolizumab dosing. We aimed to assess the impact of a TDM quality improvement (QI) initiative on 52-week clinical outcomes and describe proactively obtained vedolizumab levels during the induction period in children with inflammatory bowel disease (IBD). A QI initiative to proactively obtain TDM levels at Week 6 was implemented in 2019. A retrospective review of pediatric patients with IBD treated with vedolizumab from 2018 to 2022 was performed. Baseline demographic data, medication dosing details, disease characteristics, lab results, and 12-month clinical outcomes were recorded. For this study, we defined therapeutic target levels (>20 μg/mL at Week 6 and >12 μg/mL during maintenance) based on existing data correlating these levels with improved clinical outcomes. Fifty-nine patients (31 Crohn disease [CD], 28 ulcerative colitis [UC]/indeterminate colitis [IC]) were included in the study. In total, 68% (40/59) of patients had vedolizumab levels at Week 6and 90% (53/59) had levels drawn at Week 6 or 14. Thirty-five percent of Week 6 trough levels were below our defined target of 20 μg/mL. Fifty-two of 59 patients had available data at 52 weeks. Over 80% (42/52) of patients remained on vedolizumab 52 weeks after initiation (CD 79% [23/29], UC/IC 83% [19/23]). Sixty-two percent (26/42) of patients that remained on vedolizumab at 52 weeks were treated with an intensified dosing interval of <8 weeks. Thirty-one of these 42 (74%) were in clinical remission (CR)rate at 52 weeks with 29/42 (69%) in corticosteroid-free remission. The CR rate for the entire cohort including those who discontinued therapy due to a lack of efficacy before 52 weeks was 60% (31/52). Proactive TDM and early dose optimization with vedolizumab may improve drug durability and clinical outcomes in pediatric patients with IBD.

P964 Vedolizumab trough concentrations during subcutaneous treatment in patients with inflammatory bowel diseases

Abstract Background An exposure-response relationship has been described for intravenous (IV) vedolizumab (VDZ), but little is known about through levels and real life outcomes of subcutaneous (SC) VDZ treatment. We aimed to study the effect of SC VDZ in a prospective real life cohort and assessed what clinical variables are associated with vedolizumab trough concentrations. Methods IBD patients initiating VDZ SC treatment were included in our nationwide, prospective Initiative on Crohn and Colitis (ICC) registry. Adult IBD patients were included if a known trough level during IV and SC therapy was available. Two different assays were used for trough levels measurements : i.e. an enzyme linked immunosorbent assay (ELISA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The primary outcome measure was the mean VDZ trough concentration during maintenance treatment (after at least four SC injections). In addition, associations between VDZ serum trough concentrations and corticosteroid-free clinical remission were assessed. A Receiver Operating Characteristic (ROC) analysis was performed to determine the concentration threshold that was associated with corticosteroid free clinical remission after 4 SC VDZ injections (i.e. defined as a Harvey Bradshaw Index (HBI) score ≤ 4 for CD and a Short Clinical Colitis Activity Index (SCCAI) score ≤ 2 for UC). Results In total, 24 with Crohn’s disease (CD) and 32 with ulcerative colitis (UC) patients were included. Twelve patients started SC VDZ after a maximum of three VDZ infusions and 44 patients switched to VDZ SC after at least four VDZ infusions. The mean VDZ trough concentration was 34.4 µg/mL (SD 12.9) after 13 (IQR 11-20) weeks of SC treatment. The mean VDZ trough concentration increased from 20.5 µg/mL to 35.2 µg/mL (P &amp;lt; 0.001) in patients who switched from IV to SC VDZ. Biochemical remission (defined as a C-reactive protein (CRP) ≤ 5 µg/mL with a faecal calprotectin (FC) ≤ 250 µg/g) prior to the switch, VDZ measurements using LC-MS/MS and higher VDZ levels during IV therapy were associated with higher VDZ serum levels during SC therapy. Active smoking and prior use of &amp;gt;1 biologic and/or tofacitinib were associated with lower VDZ levels during SC therapy (table 1). A VDZ trough concentration of ≥ 34.5 µg/mL during SC maintenance therapy predicted corticosteroid free clinical remission with a sensitivity, specificity, positive predictive value and negative predictive value of 60%, 75%, 86% and 43%, respectively. Conclusion VDZ serum concentrations were significantly higher during SC therapy versus IV treatment. A VDZ trough concentrations ≥ 34.5 µg/mL was associated with corticosteroid free remission.

P935 Remission rates of biologics and small molecules in extension studies of moderate to severe Ulcerative Colitis; A systematic review and Network Meta-analysis

Abstract Background Ulcerative colitis is a relapsing and remitting inflammatory bowel disease characterised by symptoms of bloody diarrhoea and abdominal pain. In recent years, newer therapies have emerged such as biologics and small molecule therapies. However, these therapies have not been compared head-to-head in the longer term, and the choice in clinical practice is often at the discretion of the clinician. In this study we aim to compare these biologics and small molecule therapies across outcomes such as remission (as defined by the Mayo score) as well as histological, endoscopic and corticosteroid free remission in data beyond 52 weeks of medication administration. Methods Medical databases including MEDLINE, EMBASE and Cochrane were searched for phase III and IV randomised control trials examining efficacy of biologic and small molecule therapies in adults with moderate to severe ulcerative colitis beyond 52 weeks. A network meta-analysis was performed using the frequentist model to compare the aforementioned outcomes with pooled relative risk, heterogeneity and P values used to rank treatments. Results 13 randomised control trials (RCT) were included for analysis from a screen of 2516 abstracts. Of these 13 RCTs, there were 8 treatments directly compared to placebo beyond week 52. In terms of remission as defined by the Mayo score, Upadacitinib 30mg was found to be the best treatment for moderate-severe ulcerative colitis when compared to Upadacitnib 15mg, Vedolizumab and Etrolizumab in consecutive order. In achieving histological remission, Upadacitinib 30mg was superior to Upadacitinib 15mg, Filgotinib (200mg and 100mg) and Etrolizumab. For endoscopic remission, Upadacitinib 30mg was superior to Upadacitinib 15mg, Filgotinib (200mg and 100mg), Vedolizumab, Etrolizumab and Golimumab. For corticosteroid free remission, Filgotinib 200mg was superior to Golimumab, Upadacitinib (30mg and 15mg), Vedolizumab and Etrolizumab. Conclusion Large head-to-head trials of biologic and small molecule therapies in the treatment of moderate to severe ulcerative colitis beyond 52 weeks have not been performed. However, our results show Upadacitinib 30mg to be efficacious in terms of remission defined by the Mayo score as well as histologic, endoscopic and corticosteroid free remission when compared to other biologics and small molecule therapies. Whilst these newer therapies show promise, their overall performance over an extended period remains unclear and their use often precludes the efficacy of subsequent biologic or small molecule therapies. As such, the first choice of therapy must be made carefully to increase the probability of remission whilst also balancing the burden of adverse events.

P902 Subcutaneous infliximab (CT-P13 SC) as maintenance therapy for Crohn’s disease: 2 years results of the LIBERTY-CD study

Abstract Background CT-P13 subcutaneous (SC) infliximab formulation showed superiority over placebo as maintenance therapy at Week 54 in Crohn’s disease (CD)1 and ulcerative colitis2. The LIBERTY-CD study1 included an extension phase up to Week 102, the results, of which, are reported. Methods Patients who completed the maintenance phase up to Week 54 and, in the opinion of the investigator, would benefit from continued treatment could continue the open-label extension phase from Week 56 to Week 102 and received CT P13 SC 120 mg regardless of the previous assigned arm of maintenance phase. Patients who had received the adjusted dose of CT-P13 SC 240 mg during the maintenance phase continued receiving the same doses in the extension phase. At Week 54 and Week 102, clinical remission, clinical response, endoscopic remission, endoscopic response, clinical remission (alternative definition) and corticosteroid-free remission were assessed for patients who were treated CT-P13 SC during the extension phase (Figure 1.A) or who were treated CT-P13 SC during the extension phase and had valid efficacy results at the visit of interest (Figure 1.B). Patients with dose adjustment to CT-P13 SC 240 mg prior to Week 54 were considered as non-remitter/non-responder. Safety was evaluated through the extension phase. Results A total of 180 patients in the CT-P13 SC arm (assigned arm at the maintenance phase) entered into the extension phase. Overall, 85.6% (154/180) completed extension phase. Compared to the Week 54 results, efficacy results in the CT-P13 SC arm based on the non-responder imputation for missing or invalid data (i.e., patients who had missing or invalid data were considered as non-remitter/non-responder) were generally maintained in clinical remission, clinical response, endoscopic remission, endoscopic response, clinical remission (alternative definition), and corticosteroid-free remission at Week 102 (Figure 1.A). The efficacy results based on the no imputation for missing or invalid data (i.e., observed data) at Week 54 and Week 102 were similar (Figure 1.B). There was no new safety issue reported during the extension phase (Table 1). No death was reported during the extension phase. Conclusion Efficacy of CT-P13 SC was maintained through the extension phase. No new safety concerns were observed during the extension phase. These results show that CT-P13 SC provides both a long-term clinical benefit and safety with the convenience of SC administration for moderately to severely active CD patients. [1] Colombel et al., Journal of Crohn's and Colitis, 2023. [2] Sands et al., Journal of Crohn's and Colitis, 2023.