Infliximab In Ulcerative Colitis Research Articles

P761 Clinical efficacy and durability of subcutaneous infliximab in patients with moderate-to-severe inflammatory bowel disease : a real-world data from a Korean multicentre prospective cohort study

Abstract Background Subcutaneous infliximab (IFX-SC) has shown comparable efficacy and safety with IV infliximab in ulcerative colitis (UC) or Crohn's disease (CD) since its launching in 2021. We aimed to investigate the one-year real-life efficacy and durability of IFX-SC in Korea. Methods From September 2021 to November 2023, patients with moderate-to-severe UC or CD, who are naive to any types of biologic agents or IFX were prospectively enrolled from 41 tertiary referral centers in Korea. After IV infliximab induction from Week (W) 0 to W2, patients received IFX-SC every 2 weeks from W6. Patients who administered IFX-SC less than W14 were excluded. Clinical remission (CREM), clinical response (CRES) at W26, W50, and one-year drug survival were assessed. In patients with CD, CREM was defined as Crohn’s disease activity index (CDAI) <150 points, and CRES was defined as a reduction in CDAI ≥70 points from baseline. In patients with UC, CREM was defined as partial Mayo score(pMS) of ≤1 points with no individual subscore of >1 point, and CRES was defined as a reduction from baseline in pMS of ≥2 points and ≥30% along with either a reduction in rectal bleeding subscore (RBS) of ≥1 point or an absolute RBS of ≤1 point19. Drug survival was evaluated based on the time of drug persistence from W0 to the last date of IFX-SC administration among drug-off cases. Results A total of 192 patients (UC with 53, and CD with 139) were enrolled, consisting of about 80% of biologic naïve cohort. Enrolled patients included young adults with a male predominance (Table 1). At W26, patients with UC showed 54.5% CREM and 88.6% CRES (Figure 1A). Among patients with CD, rates of CREM and CRES were 92.1% and 97.0%, respectively. Similarly, W50 CREM and CRES were also favorable with a rate of 57.1% and 89.3% among UC patients. In addition, among CD patients, favorable outcome was more obvious, showing 84.6% and 93.8% of CREM and CRES. Meanwhile, one-year drug survival was also investigated. As shown on the Figure 1B, one-year drug survival probability seemed favorable with a survival rate over 97% in both UC and CD patients (UC; 98.1% at W26 with 95% confidence interval [CI], 0.874–0.852, 96.1% at W50, 95% CI, 0.852–0.990, and CD; 97.8% at W26 with 95% CI, 0.933–0.993, 97.8% at W50 with 95% CI, 0.933–0.993). During the study, 3.1% (six patients) of serious adverse events were reported. Conclusion IFX-SC seems to be efficacious therapeutic option for patients with moderate-to-severe UC or CD patients in real-world settings. With a favorable drug survival and tolerable safety profile, it may facilitate individualized treatment with a good compliance.

P558 Clinical Effectiveness and Safety of Vedolizumab vs. Infliximab in Biologic-Naïve Ulcerative Colitis Patients: A Brazilian Real-World Multicentric Observational Study

Abstract Background Vedolizumab (VDZ) and infliximab (IFX), are considered first-line agents in the treatment of moderate to severe Ulcerative Colitis (UC). However, there are no head-to-head studies comparing the relative effectiveness of the two agents, and Real-world data on the effectiveness and safety of VDZ and IFX in UC are lacking in the Brazilian population. We aimed to compare effectiveness and safety of VDZ to IFX in Biologic-naïve UC patients. Methods We conducted a multicenter retrospective cohort study, including patients with moderate to severe UC (Total Mayo score 6-12, with an endoscopic subscore of 2 or 3) who treated with VDZ or IFX. The primary endpoints were: clinical remission, defined as a partial Mayo score (PMS) ≤2, endoscopic remission (endoscopic Mayo subscore of 1 or 0) and steroid-free clinical remission at week 52. Secondary endpoints included; clinical response at weeks 12 and 26, need for drug optimization, adverse events (AEs), need for hospitalization and colectomy, loss of response and biochemical remission (C-reactive protein [CRP] ≤ 0.5 mg/dl and/or fecal calprotectin [FC] ≤ 150 mcg/g) at week 52. Results A total of 174 UC (79 VDZ and 95 IFX) patients were included. Clinical remission and endoscopic remission at week 52 were achieved by 56 (70.8% vs 68.4%, p= 0.44) and 46 (58.2% vs 55.7%, p=0.18) of VDZ and IFX patients, respectively. Steroid-free clinical remission at week 52 was 84.2% and 54.1% in the VDZ and IFX group, respectively (p = 0.03). Clinical response at weeks 12 and 26 was reached in 80.0% vs 76.2%, p = 0.74 and in 71.4% vs 77.3%, p = 0.71 in the VDZ and IFX group, respectively. The need for drug optimization was higher for IFX than for VDZ (36.8% vs. 21.5%, p = 0.03). The incidence of AEs (26.3% vs 12.6%, p=0.03) and need for hospitalization (26.3% vs 11.4%, p=0.02) were higher for IFX than to VDZ patients. Secondary loss of response was similar in the two groups (16.4 % for VDZ and 16.8% for IFX, p = 1.00). Biochemical remission at week 52 was 75.0% for VDZ, and 63.9% for IFX, respectively (p=0,42). Conclusion In this real-world study VDZ and IFX had similar efficacy in inducing clinical remission, endoscopic remission, clinical response and biochemical remission at week 52. Compared to IFX, VDZ was superior in inducing steroid-free remission, in addition to having a better safety profile and less need for dose escalation. Both VDZ and IFX were effective treatment options in bio-naïve UC patients.

Prediction and Verification of Potential Therapeutic Targets for Non-Responders to Infliximab in Ulcerative Colitis.

Infliximab (IFX) has been widely used in ulcerative colitis (UC) patients. However, the subsequent effective treatment of IFX non-response in UC patients remains a challenge. This study aims to predict potential therapeutic targets for non-responders by performing a bioinformatic analysis of the data in the Gene Expression Omnibus (GEO) database and validation by biopsies. Colonic mucosal biopsies expression profiles of IFX-treated UC patients (GSE73661, GSE16879) were utilized to predict potential therapeutic targets. Bioinformatics analyses were used to explore potential biological mechanisms. CytoHubba was performed to screen hub genes. We used a validation dataset and colonic mucosal biopsies of UC patients to validate hub genes. A total of 147 DEGs were identified (119 upregulated genes and 28 downregulated genes). GSEA showed that DEGs in GSE73661 were enriched in the pathways of the cytokine-cytokine receptor, the chemokine, and the adhesion molecules system. Based on the PPI network analysis, we identified four hub genes (and the transcription factor NF-κB). Then, we validate the expression of hub genes by reverse transcription-polymerase chain reaction (RT-PCR). We found higher expression of IL-6, IL1B, CXCL8, and CCL2 in non-responders compared to responders. In summary, four potential targets (IL-6, IL1B, CXCL8, and CCL2) were finally identified by performing a bioinformatics analysis of the datasets in the GEO database. Their expression was confirmed in colonic mucosal biopsies of patients with UC. These results can help to further explore the mechanism of non-responders to IFX in UC and to provide potential targets for their subsequent treatment.

P564 vedolizumab versus infliximab and adalimumab in the real-world persistence in Ulcerative Colitis and Crohn’s disease – a meta-analysis

Abstract Background In Ulcerative Colitis (UC), vedolizumab demonstrated increased efficacy over adalimumab in the VARSITY study. However, the real-world effectiveness of vedolizumab against adalimumab, infliximab and in UC and Crohn’s disease (CD) is not well-known. Drug persistence measures the duration of time from initiation to discontinuation of a therapy, is a surrogate marker that combines therapeutic efficacy, safety, and tolerability. This meta-analysis compared drug persistence of vedolizumab versus anti TNF alpha inhibitors (TNFi) adalimumab and infliximab in UC and CD. Methods Systematic review and meta-analysis were conducted with observational studies identified in electronic database – EMBASE and PubMed search from inception of 2017 to July 2022 and abstracts screened from recent gastroenterology conference – Digestive disease week 2022 San Diego. 6 observational studies evaluating persistence of vedolizumab versus TNFi (infliximab and adalimumab) among participants aged >18 years with diagnosis of IBD met inclusion criteria and were included. Results Overall, 1 year persistence of vedolizumab is 71.2% in UC and 76% in CD, significantly higher than infliximab (56.4% in UC, 53.7% in CD) and adalimumab (53.7% in UC, 55.6% in CD). (Table 1) Head-to-head comparison shows RR of 1.15 (95% CI of 1.12 – 1.19), favouring vedolizumab. 2-years persistence was pooled from 4 studies. Vedolizumab had a 2-years persistence of 66% in UC and 61% in CD, which also shows superiority to both infliximab (49.7% for UC, 59.1% for CD) and adalimumab (31.4% for UC and 56% for CD). (Table 2) Meta-analysis with head-to-head comparison continue to show a statistically significant difference in 2 years persistence of vedolizumab versus TNFi (RR of 1.12, 95% CI 1.01 – 1.25). For UC patients, vedolizumab shows superiority over both adalimumab and infliximab with a RR of 1.41 (95% CI 1.14 – 1.74) and 1.15 (95% CI 1.06 – 1.25) respectively and RR of 1.23 (CI 1.14 – 1.33) when adalimumab and infliximab combined. For CD, vedolizumab has a slightly higher 1-year persistence over TNFi combined (RR 1.10 95% CI 1.02 – 1.19) but fails to show any statistically significant difference from adalimumab (RR 1.07 95% CI 0.86 – 1.32) and infliximab (RR 0.55 95% CI 0.07 – 4.35) individually. Vedolizumab has a higher 1-year persistence in bio-naïve subgroup (RR 1.14 95% CI 1.07 – 1.22) but fails to show statistically significant advantage in bio-experienced group (RR 1.04 95% CI 0.80 – 1.35) when compare with TNFi. Conclusion Vedolizumab achieved a higher overall 1- and 2-years persistence compared to adalimumab and infliximab in both CD and UC but mainly in bio-naïve subjects. The benefit of vedolizumab over TNFi was more evident in UC than CD.

Novel Gene Signatures Predicting Primary Non-response to Infliximab in Ulcerative Colitis: Development and Validation Combining Random Forest With Artificial Neural Network.

Background: While infliximab has revolutionized the treatment of ulcerative colitis, primary non-response is difficult to predict, which limits effective disease management. The study aimed to establish a novel genetic model to predict primary non-response to infliximab in patients with ulcerative colitis.Methods: Publicly available mucosal expression profiles of infliximab-treated ulcerative colitis patients (GSE16879, GSE12251) were utilized to identify potential predictive gene panels. The random forest algorithm and artificial neural network were applied to further screen for predictive signatures and establish a model to predict primary non-response to infliximab.Results: A total of 28 downregulated and 2 upregulated differentially expressed genes were identified as predictors. The novel model was successfully established on the basis of the molecular prognostic score system, with a significantly predictive value (AUC = 0.93), and was validated with an independent dataset GSE23597 (AUC = 0.81).Conclusion: Machine learning was used to construct a predictive model based on the molecular prognostic score system. The novel model can predict primary non-response to infliximab in patients with ulcerative colitis, which aids in clinical-decision making.

Efficacy of Infliximab after Failure of Subcutaneous Anti-TNF Agents in Patients with Moderate to Severe Ulcerative Colitis

Aim: To assess the efficacy of infliximab in ulcerative colitis (UC) patients who had failed therapy with adalimumab or golimumab. Methods: Retrospective analysis of prospectively acquired data of all anti-TNF naive patients with moderate to severe UC who received adalimumab or golimumab in 4 tertiary referral centres. Patients with primary non response or secondary loss of response to adalimumab or golimumab received therapy with infliximab. Clinical response and remission rates were assessed at week 14 and 54 after initiation of infliximab. Results: Between September 2015 and September 2017, 29 of 58 (50%) anti-TNF naive patients with moderate to severe UC failed therapy with adalimumab (n=38) or golimumab (n=20). Twenty one of 29 (72.4%) patients were primary non responders and 8 (27.6%) patients lost response to adalimumab or golimumab. All these 29 patients received infliximab, while 15 (51.7%) were on concomitant azathioprine therapy. Eighteen (62.1%) and 10 (34.5%) patients showed clinical response and clinical remission at week 14 respectively, while 14 (48.3%) patients were on clinical remission at week 54 after initiation of infliximab. Azathioprine co-administration at the start of infliximab was associated with a greater proportion of patients achieving clinical remission at week 54 (10 of 15 patients on combination therapy vs 4 of 14 patients on infliximab monotherapy, p=0.04). Conclusions: A significant proportion of anti-TNF naive patients with moderate to severe UC who have failed 1st course therapy with subcutaneous anti-TNF agents can achieve clinical response and/or remission with 2nd course therapy with infliximab.

DOP39 The first prospective, multicentre, randomised controlled trial on discontinuation of infliximab in ulcerative colitis in remission; endoscopic normalisation does not guarantee successful withdrawal

Abstract Background Anti-tumour necrosis factor (TNF)-α agents are the mainstay of the long-term treatments for refractory ulcerative colitis (UC). However, there is no prospective randomised controlled trial evaluating if anti-TNF-α agents can be discontinued in UC patients in remission. Methods Patients with UC maintained in clinical remission with infliximab (IFX) were prospectively enrolled from 23 specialist centres. Patients confirmed to be in (1) clinical remission for > 6 months, (2) steroid-free and (3) Mayo endoscopic subscore (MES) of 0 or 1 were randomised with stratified factors (MES and use of immunomodulators) into two groups (continue or discontinue IFX) in 1:1. The biopsy was taken from the rectum and Nancy histological Index (NI) was centrally scored at randomisation. The primary endpoint was remission rate at week 48 in full analysis set (FAS). Factors associated with remission at Week 48 were evaluated by logistic regression adjusted for the treatment group. Efficacy and safety of retreatment with IFX after relapse were also evaluated. Results A total of 92 patients were included in the FAS and the remission rates at week 48 were 80.4% (95% CI: 66.1–90.6) and 54.3% (95% CI: 39.0–69.1) in IFX-continued and IFX-discontinued groups, respectively (p = 0.008). Although the duration of IFX, use of concomitant immunomodulators, IFX concentration, and MES of 0 at randomisation were not predictive, C-reactive protein and NI were associated with remission at week 48 in FAS (p = 0.039 and 0.019, respectively). Retreatment with IFX lead to remission in 8 out of 12 patients (66.7%) in 8 weeks and was well-tolerated. Conclusion This first prospective multicentre randomised controlled trial confirmed that discontinuation of maintenance IFX resulted in the increased risk of relapse but retreatment was effective in UC. Endoscopic normalisation was not sufficient for the successful discontinuation of IFX.

Pooled analysis of the comparative efficacy between tacrolimus and infliximab for ulcerative colitis.

Acute moderate-to-severe steroid-refractory ulcerative colitis (UC) has a poor prognosis and requires optimal rescue therapy. A pooled analysis was conducted to assess tacrolimus and infliximab (IFX) as rescue agents in patients with moderate-to-severe and steroid-refractory UC. A literature search identified studies that investigated tacrolimus and IFX in moderate-to-severe steroid-refractory patients with UC. The primary outcome was short-term clinical response to treatment, including the remission and response rates. Secondary outcomes included the rates of colectomy at 3 months and adverse events rate. A total of 6 studies comprising 438 cases were eligible for inclusion. The pooled analysis showed that the short-term clinical response rate, clinical remission rate, and 3-month colectomy rate were 72.1%, 52.4%, and 10.1%, respectively, for those receiving tacrolimus, and 76.9%, 48.8%, and 12.4%, respectively, for those receiving IFX. No significant difference was, however, seen for tacrolimus compared with IFX with regard to clinical remission rate (odds ratio [OR] =1.08, 95% confidence interval [CI] = 0.77-1.49, P = .67), clinical response rate (OR = 0.92, 95% CI = 0.63-1.34, P = .66), and 3-month colectomy rate (OR = 0.86, 95% CI = 0.39-1.93, P = .72). More adverse events were, however, observed in the Tac group (OR = 2.16, 95% CI = 1.25-3.76, P = .006). Our meta-analysis suggested that both tacrolimus and IFX appeared to be effective and safe for the rescue therapy of moderate-to-severe active UC and steroid-refractory UC. Therefore, tacrolimus is another choice for these patients.

P733 Serum interleukin-6 level predicts future outcomes of infliximab for ulcerative colitis

P733 Serum interleukin-6 level predicts future outcomes of infliximab for ulcerative colitis

A biological network-based regularized artificial neural network model for robust phenotype prediction from gene expression data

BackgroundStratification of patient subpopulations that respond favorably to treatment or experience and adverse reaction is an essential step toward development of new personalized therapies and diagnostics. It is currently feasible to generate omic-scale biological measurements for all patients in a study, providing an opportunity for machine learning models to identify molecular markers for disease diagnosis and progression. However, the high variability of genetic background in human populations hampers the reproducibility of omic-scale markers. In this paper, we develop a biological network-based regularized artificial neural network model for prediction of phenotype from transcriptomic measurements in clinical trials. To improve model sparsity and the overall reproducibility of the model, we incorporate regularization for simultaneous shrinkage of gene sets based on active upstream regulatory mechanisms into the model.ResultsWe benchmark our method against various regression, support vector machines and artificial neural network models and demonstrate the ability of our method in predicting the clinical outcomes using clinical trial data on acute rejection in kidney transplantation and response to Infliximab in ulcerative colitis. We show that integration of prior biological knowledge into the classification as developed in this paper, significantly improves the robustness and generalizability of predictions to independent datasets. We provide a Java code of our algorithm along with a parsed version of the STRING DB database.ConclusionIn summary, we present a method for prediction of clinical phenotypes using baseline genome-wide expression data that makes use of prior biological knowledge on gene-regulatory interactions in order to increase robustness and reproducibility of omic-scale markers. The integrated group-wise regularization methods increases the interpretability of biological signatures and gives stable performance estimates across independent test sets.

Unusual case of a young man with multifocal encephalitis in the context of remote treatment with azathioprine and infliximab for ulcerative colitis – clinical, MRI, neuropathology findings, and exquisite steroid-responsive course (P1.338)

Unusual case of a young man with multifocal encephalitis in the context of remote treatment with azathioprine and infliximab for ulcerative colitis – clinical, MRI, neuropathology findings, and exquisite steroid-responsive course (P1.338)

P.11.13: Bowel Ultrasound and Faecal Calprotectin as Predictors of Response to Infliximab in Ulcerative Colitis

P.11.13: Bowel Ultrasound and Faecal Calprotectin as Predictors of Response to Infliximab in Ulcerative Colitis

P-092 Economic Impact of Infusion Administration Time Billing for Vedolizumab and Infliximab for Ulcerative Colitis and Crohn's Disease: Health Plan Perspective

P-092 Economic Impact of Infusion Administration Time Billing for Vedolizumab and Infliximab for Ulcerative Colitis and Crohn's Disease: Health Plan Perspective

Accuracies of fecal calprotectin, lactoferrin, M2-pyruvate kinase, neopterin and zonulin to predict the response to infliximab in ulcerative colitis

BackgroundFecal markers might predict the response to anti-TNFα in ulcerative colitis (UC). AimsTo compare the performance of fecal calprotectin (fCal), lactoferrin (fLact), M2-PK (fM2-PK), neopterin (fNeo), and zonulin (fZon) to predict the response to therapy in active UC patients. MethodsDisease activity from 31 consecutive patients with an active UC, treated with infliximab (IFX) was assessed by the Mayo score at baseline and at week 14 and by the partial Mayo score at W52 and stool samples collected for fecal marker measurements at W0, W2, and W14. ResultsAt W14, 19 patients (61%) were responders to IFX induction. The median levels of fCal, fLact and fM2-PK drop dramatically from baseline to W14 in clinical responders. At W2, fM2-PK, fLact and fCal levels predicted accurately the response to IFX induction. At W14, fLact, fCal, and fM2-PK were individually reliable markers to predict sustained response at W52. The performances of fNeo and fZon were weaker in this setting. ConclusionsThe performance of fM2-PK at W2 to predict response to induction therapy with IFX was superior to that of fLact and fCal, whereas monitoring fLact was the best tool to predict adequately the course of the disease at one year under maintenance IFX in UC.

PTU-072 Discontinuation of Infliximab in Patients with Ulcerative Colitis is Associated with Increased Risk of Relapse: A Multinational Retrospective Cohort Study

Introduction Efficacy and safety of infliximab in ulcerative colitis (UC) is well-established. We conducted a multicenter retrospective cohort study across 7 European countries, and Israel, to examine whether infliximab discontinuation can be considered for patients who achieve sustained remission. Methods The disease course of patients who discontinued infliximab was compared against that of patients who continued scheduled treatment (control group). We examined the incidence rates of relapse, hospitalisation and colectomy, the comparative effectiveness of different therapeutic strategies after discontinuation, and assessed the rates of response, remission and adverse effects after infliximab re-initiation. Statistical analyses employed time-to-event methods Results In total, 193 patients were included, 111 discontinued infliximab. The incidence rate of relapse was significantly higher after discontinuation (23.3 per 100 person-years) as compared to the control group (7.2 per 100 person-years) both in univariable (log-rank p Conclusion Infliximab discontinuation in UC patients with sustained clinical remission is associated with increased risk of relapse. Treatment re-initiation is effective and safe. Disclosure of Interest G. Fiorino Consultant for: MSD, AbbVie, Takeda, Janssen, Mundipharma, Sandoz, Pfizer, P. Cortes: None Declared, P. Ellul Grant/research support from: MSD, AbbVie, C. Felice Consultant for: MSD, AbbVie, P. Karatzas: None Declared, M. Silva: None Declared, P. Lakatos Grant/research support from: MSD, AbbVie, Hospira, Consultant for: MSD, AbbVie,Celltrion, EGIS, Falk Pharma GmbH, Ferring, Genentech, Hospira, F. Bossa Consultant for: MSD, Abbvie, Mundipharma, and Takeda, S. Sebastian Grant/research support from: MSD, AbbVie, Speaker bureau with: MSD, B. Ungar: None Declared, F. Furfaro: None Declared, K. Karmiris Consultant for: MSD, AbbVie, Takeda, K. Katsanos: None Declared, M. Muscat: None Declared, D. Christodoulou: None Declared, G. Maconi: None Declared, U. Kopylov Consultant for: Janssen, Abbvie, Takeda and CTS, F. Magro: None Declared, G. Mantzaris: None Declared, A. Armuzzi Grant/research support from: MSD, Consultant for: Abbvie, Celltrion, Ferring, Hospira, Janssen, Lilly, MSD, Mundipharma, Pfizer, Sofar, Takeda, M. M. Bosca-Watts: None Declared, S. Ben-Horin Grant/research support from: AbbVie and Celltrion, Consultant for: AbbVie, Celltrion, Janssen, Takeda and Schering-Plough, S. Bonovas: None Declared, S. Danese Consultant for: Schering-Plough, Abbott Laboratories, Merck, UCB-pharma, Ferring, Cellerix, Millenium Takeda, Nycomed, Pharmacosmos, Actelion, Danone, Alpha Wasserman, Genentech, Grunenthal, Pfizer, Astra Zeneca, Novo Nordisk, Cosmo Pharmaceuticals, Vifor, and Johnson & Johnson, Speaker bureau with: Schering-Plough, Abbott Laboratories, Merck, UCB-pharma, Ferring, Cellerix, Millenium Takeda, Nycomed, Pharmacosmos, Actelion, Danone, Alpha Wasserman, Genentech, Grunenthal, Pfizer, Astra Zeneca, Novo Nordisk, Cosmo Pharmaceuticals, Vifor, and Johnson & Johnson

PTH-080 Serious Infusion Reactions with Vedolizumab are Rare: A UK Multicenter Experience

Introduction Vedolizumab has recently become widely available in the UK for the treatment of moderate to severe ulcerative colitis (UC) and Crohn’s disease (CD). This has created pressure on infusion services exacerbated by the improved access to infliximab for UC and the ever increasing number of patients with CD receiving IFX. The UK Summary of Product Characteristics, unlike in the US, mandates post-infusion monitoring of patients for 2 hours after the first 2 infusions and for 1 hour after subsequent infusions. We have, therefore, reviewed the frequency of infusion reactions during and after infusions of vedolizumab in 6 UK IBD centres. Methods Details of the numbers of vials of vedolizumab supplied to each centre were provided by Takeda UK. All centres identified patients on vedolizumab who had had possible infusion-related reactions and reported the details after review of the case record. Results Across the 6 centres, 1132 vials of vedolizumab had been supplied for infusion up until 5th March 2016. 9 possible infusion reactions were identified involving 9 patients. 1 reaction occurred during the infusion, 1 in the 2 hours after the infusion and 7 more than 2 hours after the infusion. One anaphylactoid reaction occurred on the second infusion in a patient with Crohn’s disease on concomitant mercaptopurine. The infusion was stopped and no further infusions of vedolizumab were given. Other possible infusion-related reactions included headache (2), rash (3), nausea and blurred vision (1), vasovagal symptoms (1), and palpitations (1). Only one reaction occurred in the 2 hours following the infusion. This was a patient who experienced palpitations who had consumed several cups of coffee whilst waiting to be discharged. Other than the patient with an anaphylactoid reaction, none of the other reactions led to discontinuation of vedolizumab. Conclusion Vedolizumab infusion reactions are rare. Only one anaphylactoid reaction was seen in over 1000 infusions. No definite reactions occurred in the 2 hours after infusions suggesting that monitoring patients for 2 hours after the first 2 infusions and for 1 hour after subsequent infusions is probably unnecessary. Overall, the frequency of infusion reactions is low as was seen in the Gemini studies. Disclosure of Interest P. Irving Grant/research support from: AbbVie, MSD, Consultant for: AbbVie, MSD, Vifor, Genentech Inc., Takeda, Warner Chilcott, Falk and Pharmacosmos, Speaker bureau with: AbbVie, MSD, Ferring, Warner Chilcott, Shire, Falk and Johnson and Johnson, C. Lees: None Declared, A. Hart: None Declared, K. Kemp: None Declared, T. Ahmad: None Declared, F. Cummings: None Declared

Long-Term Follow-Up of Patients Treated with Infliximab for Ulcerative Colitis: Predictive Factors of Response—An Observational Study

To evaluate the early and long-term efficacy of infliximab in ulcerative colitis and to determine predictors of response and colectomy. This is an ambidirectional cohort study in a tertiary referral center including patients who started infliximab within 2005 and 2008 and monitored until 2014. Efficacy was evaluated by partial Mayo scores at weeks 2, 4, 8, 30, and 54. Long-term treatment maintenance with infliximab and colectomy requirements were recorded. Fifty-three patients were included with a median follow-up of 69.5months. Clinical remission at the time point assessments was 40.8, 47.2, 54.7, 54.7, and 49.1%. At the time of maximal follow-up, the proportion of patients under infliximab maintenance was 24.5%. A higher level of albumin (OR 1.4, CI 95% 1.06-1.8; p=0.017) was predictive of a higher remission rate at week 8. Concomitant immunomodulators beyond 6months were predictive of infliximab's long-term maintenance (OR 15.8, CI 95% 1.8-135.4; p=0.012). Colectomy was required in 41.5%. Factors associated with a higher rate of colectomy at week 54 were previous treatment with cyclosporine (OR 3.4, CI 95% 1.2-9.7; p=0.012), absence of response at week 8 (OR 10.3, CI 95% 3.3-31.7; p<0.001), and not receiving concomitant immunomodulators (OR 4.1, CI 95% 1.8-9; p=0.002). Colectomy rates within the first 54weeks were closely dependent on the number of variables present: none (0%), 1 (26.3%), 2 (71.4%), or 3 (100%) of them (log rank <0.0001). Low albumin, previous treatment with cyclosporine, absence of a concomitant immunomodulator, and lack of response at week 8 negatively affected the efficacy of infliximab in ulcerative colitis.

Long-term assessment of clinical response to adalimumab therapy in refractory ulcerative colitis

The role of antitumour necrosis factor agents, in particular infliximab in ulcerative colitis (UC) has been well established. More recently adalimumab, a fully humanized antitumour necrosis factor α monoclonal antibody, was licensed for refractory moderately active UC in 2012. Available outcome data for adalimumab from routine clinical practice is limited. To evaluate the clinical response and remission to adalimumab in a cohort of UC patients. Patients with UC treated with adalimumab were identified from our inflammatory bowel disease database from 2007. A retrospective chart review was undertaken. Demographic and clinical data were recorded including a Mayo score and C-reactive protein (CRP) where available. All patients received standard induction subcutaneous therapy (160/80/40 mg) followed by a maintenance dose of 40 mg fortnightly. Clinical and biochemical response was assessed at 6 and 12 months. Clinical response was defined by a reduction in Mayo score more than or equal to 3, whereas clinical remission was defined by a total score of 2 or less. Dose adjustments and adverse events were also noted. In all, 52 patients were identified. Of these, 65% (n=34) were male and the mean age was 45 years (range 23-72 years). A total of 65% (n=34) had left sided disease, 31% (n=16) pancolitis and 4% (n=2) proctitis. The majority commenced adalimumab due to a loss of response to immunomodulator therapy (n=45, 87%), whereas the remaining 13% (n=7) had loss of response or been intolerant to infliximab. The mean disease duration was 8 years (1-29 years). At baseline 85% (n=44) had moderate disease and 15% (n=8) had mild disease. The baseline mean CRP was 13.5 mg/l (range 1-82 mg/l) and the mean Mayo score was 6 (range 4-10). The mean duration of treatment was 18.5 months (range 4-95 months). Follow-up data was available in 46 (88%) and 37 (71%) patients at 6 and 12 months. Overall there was a statistically significant improvement in mean partial Mayo score on follow-up; 6 months=2 [P=0.0001, 95% confidence interval (CI) 2.99-4.55], 12 months=2 (P=0.0001, 95% CI 2.74-4.46). While 65% (n=34) and 52% (n=27) had a clinical response at 6 and 12 months, respectively, 52% (n=27) and 42% (n=22) were in remission. Overall mean CRP normalized at 6 months (P=0.002, 95% CI 3.31-15.1). Of note 25% (n=13) required dose escalation during follow-up, while treatment was discontinued by seven patients, five (71%) due to a loss of response, the remaining two (29%) due to an adverse event. Our study shows adalimumab is an effective and safe long-term therapy for moderately active UC refractory to other treatments. While this data is encouraging, further work is required on patient selection and to determine the impact of treatment on both natural history and quality of life.

Infliximab in ulcerative colitis: real-life analysis of factors predicting treatment discontinuation due to lack of response or colectomy: ECIA (ACAD Colitis and Infliximab Study)

Objective. To describe clinical practice with infliximab (IFX) in ulcerative colitis (UC); identification of predictive factors for IFX treatment discontinuation due to insufficient response and for colectomy. Material and methods. Retrospective, multicentric and observational study including every UC IFX-treated patient in 10 Spanish hospitals. Variables analyzed: epidemiological data; variables for poor prognosis; IFX prior treatments; characteristics of the IFX treatment; time from the UC diagnosis to induction with IFX; time from induction to colectomy or until data collection. Predictive and protective factors for IFX discontinuation due to lack of response and for colectomy were analyzed with binary logistic regression and Cox analysis. Results. Follow-up time from induction with IFX to the collection of data or colectomy: 36.7 ± 25.7 months. Prior treatment with immunomodulator medications (IMM): 79%; IFX + immunosuppressant therapy: 77%; discontinuation of IFX: 26%, colectomy 16%. Independent predictive or protective factors for IFX discontinuation: IMM resistance (OR: 2.9, p = 0.022, 95%CI: 1.2–7.2), prior use of leukocytapheresis (OR: 3.3, p = 0.024, 95%CI: 1.1–9.4), IFX + IMM therapy (OR: 0.3, p = 0.022, 95%CI: 0.1–0.9, and HR: 0.4, p = 0.006, 95%CI: 0.2–0.8) and corticosteroid use in induction (HR: 1.9, p = 0.049, 95%CI: 1.0–3.8). Independent predictive or protective factors for colectomy: Use of leukocytapheresis (OR: 3.0, p = 0.036, 95%CI: 1.1–8.4), IFX + IMM therapy (OR: 0.3, p = 0.022, 95%CI: 0.1–0.8, and HR: 0.3, p = 0.011, 95%CI: 0.1–0.8) and severe cortico-resistant flare-up (HR: 2.5, p = 0.032, 95%CI: 1.1–5.9). Conclusions. Prior use of IMM and leukocytapheresis, the use of corticosteroids in induction and a severe cortico-resistant flare predict a worse response to IFX and the need for colectomy. Combination therapy is a protective factor for both.

PTH-065 The impact of changes to the nice guideline on the use of biologic agents in ulcerative colitis in a uk district general hospital: Abstract PTH-065 Table 1

<h3>Introduction</h3> After pressure from patient and clinical groups NICE have reversed their position on biologics^1,2in subacute ulcerative colitis (UC) and it will be available to patients in 2015. <h3>Method</h3> A retrospective review of the use of infliximab for the treatment of UC in a single centre DGH between 2011 and 2014. <h3>Results</h3> Ten patients received infliximab for acute severe UC and ten for subacute UC. In the 12 months pre-infliximab these patients received 40 courses of prednisolone between them (Table 1). All subacute patients had received immunomodulators. All subacute patients had a partial or complete clinical (MAYO score) and biochemical response following infliximab induction, compared to 50% of the acute severe group. Two patients remain on long-term infliximab and in remission. Colectomy was required within 12 months for 55.6% of patients with acute severe disease and 44.4% of those with subacute activity. 60% of the remaining subacute patients (n = 3) have received steroids since infliximab. <h3>Conclusion</h3> NICE change of position²echos current practice in our centre and with the change in guidelines we may hope to see a reduction in steroid use prior to the use of biological treatment. However the long term success of infliximab in UC is limited. Subacute patients showed better immediate outcomes in terms of biochemical and clinical response, but at 12 months, outcomes were similar in both groups. Work is needed to identify the likely responders to make its use cost effective and evidence based guidance is needed on the clinical benefits of switching to alternative biological agents if infliximab fails. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Infliximab for acute exacerbations of ulcerative colitis. Available at: https://www.nice.org.uk/guidance/ta163. Accessed on 07/01/2015 Ulcerative colitis (moderate, severe) – infliximab (review TA140), adalimumab (review TA262) &amp; golimumab (2nd line) [ID695]. Available at: http://www.nice.org.uk/Guidance/InDevelopment/GID-TAG357. Accessed on 23/02/2015