Corticosteroid-free Clinical Remission Research Articles

Corticosteroid Use in Randomized Clinical Trials of Biologics and Small Molecules in Inflammatory Bowel Disease: A Systematic Review.

This systematic review aims to elucidate the use of corticosteroids in randomized clinical trials (RCTs) evaluating biologics and small molecules for inflammatory bowel disease (IBD). We analyzed corticosteroid use during both the induction and maintenance phases, highlighting areas needing standardization and improvement in clinical research. We selected placebo-controlled phase 3 RCTs involving adults with moderate to severe IBD. These studies included detailed reports on corticosteroid use during induction and maintenance phases, with clinical remission and/or corticosteroid-free clinical remission (CSF-CR) as primary endpoints. Initially, 324 studies were identified and refined to 26 RCTs after screening. Analysis revealed variability in corticosteroid administration. Over time, corticosteroid use showed a decreasing trend (Spearman ρ = -0.42, P = .045). Studies allowing higher corticosteroid doses (up to 40mg/day of prednisone or equivalent) reported a higher proportion of corticosteroid users (51.8%, range: 42.9%-61%) compared to those excluding patients on doses >20mg/day (37.5%, range: 31.6%-51.8%; P = .007) or >30mg/day (41.1%, range: 29.6%-53.7%; P=.023). Trials with mandatory tapering protocols showed a narrower gap between overall clinical remission and CSF-CR rates, with an average difference of 6% in the group without mandatory tapering and 1.2% in the group with forced tapering (T-test P=.038; Cohen's d ≈ 1.1). This review highlights the variability in corticosteroid use across RCTs and its impact on evaluating new IBD therapies. Standardizing tapering protocols and defining CSF-CR are essential for accurate outcomes.

Efficacy of vedolizumab and ustekinumab in pediatric-onset inflammatory bowel disease: A real-world multicenter study.

Vedolizumab and ustekinumab are effective in inducing and maintaining corticosteroid-free clinical remission (CFR) in adult patients with inflammatory bowel disease (IBD). This study describes the efficacy and safety of vedolizumab and ustekinumab in pediatric IBD. All patients ≤18 years of age with Crohn's disease (CD) or ulcerative colitis (UC) treated with vedolizumab or ustekinumab in three centers in Northern France were followed retrospectively. The primary outcome was CFR at Week 14 (W14). Twenty-five patients (9 CD, 16 UC) and 33 patients (28 CD, 5 UC) were started on vedolizumab and ustekinumab respectively between 2016 and 2021. All were previously treated with antitumor necrosis factor (TNF). The median time from diagnosis to treatment initiation was 21.0 (12.0-44.0) and 42.0 (22.0-73.5) months for vedolizumab and ustekinumab respectively. Among vedolizumab-treated patients, 36% were in CFR at W14, including 22% in CD and 44% in UC. At W52, 56% were in CFR, including 33% in CD and 69% in UC. Among ustekinumab-treated patients, 49% were in CFR at W14, including 54% in CD and 20% in UC. At W52, 55% were in CFR, including 57% in CD and 40% in UC. There was a significant increase in median growth velocity between W0 and W52 of +2 SD in vedolizumab-treated patients (p = 0.0002). Four adverse events were reported during vedolizumab treatment, none for ustekinumab-treated patients. Vedolizumab and ustekinumab appear to be effective in inducing and maintaining CFR in pediatric-onset IBD. Randomized controlled trials are needed to confirm these results.

Safety and efficacy of S1P receptor modulators for the induction and maintenance phases in inflammatory bowel disease: A systematic review and meta-analysis of randomized controlled trials.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition that significantly affects quality of life. Conventional treatments have had limited success. this study evaluates the safety and efficacy of Sphingosine 1-phosphate receptor modulators (S1PrMs) as a potential treatment for IBD. We conducted a thorough search of published literature on PubMed, EMBASE, and Google Scholar from 2000 to 2023. The inclusion criteria were randomized controlled trials (RCTs) with a target population comprising of IBD patients receiving either S1PrMs or placebo and a comparison of the 2. The statistical analysis was conducted using RevMan (version 5.4). Forest plots presented the results as risk ratios (RR) with a 95% confidence interval. A total of 7 RCTs involving 2471 patients were included. The results were reported for both the induction and maintenance phases of treatment. in the induction phase, the intervention group proved to have a significantly higher incidence of histological remission (RR = 2.67; 95% CI [1.97, 3.60]; P < .00001), endoscopic improvement (RR = 2.06; 95% CI [1.66, 2.56]; P < .00001), clinical remission (RR = 2.23; 95% CI [1.43, 3.46]; P < .0004) and clinical response (RR = 1.37; 95% CI [1.01, 1.84]; P = .04) compared to the placebo group. Outcomes assessed in maintenance phase significantly favored the intervention group over placebo as well, histologic remission (RR = 2.39; 95% CI [1.83, 3.11]; P < .00001), endoscopic improvement (RR = 2.20; 95% CI [1.28, 3.77]; P = .004), clinical remission (RR = 3.03; 95% CI [1.84, 4.99]; P < .0001), and clinical response (RR = 1.74; 95% CI [1.25, 2.42]; P = .001). S1PrMs show promising potential for establishing histologic remission, endoscopic improvement, clinical remission, and corticosteroid-free clinical remission. With more studies and clinical trials, these modulators may become a reliable therapeutic choice for UC patients everywhere.

Nordic inflammatory bowel disease treatment strategy trial: protocol for the NORDTREAT randomised controlled biomarker-strategy trial

IntroductionThe absence of reliable prognostic markers poses a challenge to the management of inflammatory bowel disease (IBD). Patients with aggressive disease may not receive sufficient treatment with conventional ‘step-up’ therapy,...

Efficacy and safety of risankizumab by baseline corticosteroid use and achievement of corticosteroid-free clinical and endoscopic outcomes in patients with moderately to severely active Crohn's disease.

Risankizumab is efficacious and well tolerated in adults with moderately to severely active Crohn's disease (CD). To evaluate the corticosteroid-sparing effect of risankizumab in CD. During the 12-week induction period, patients maintained stable baseline corticosteroid doses, up to 20 mg/day prednisone or equivalent. At week 0 of maintenance, a mandatory corticosteroid taper was started. This post hoc analysis evaluated corticosteroid-free clinical and endoscopic outcomes at week 52 of maintenance; safety was also assessed. Of 889 patients randomised to induction with risankizumab 600 mg or placebo, 285 (32.1%) were taking baseline concomitant corticosteroids. Week 12 clinical remission and endoscopic response rates were greater for risankizumab 600 mg versus placebo, regardless of concomitant corticosteroid use. At week 52, 66.7%, 50.0% and 41.2% of patients taking risankizumab 180 mg, risankizumab 360 mg and (withdrawal) placebo, respectively, discontinued corticosteroids. Week 52 corticosteroid-free clinical remission per stool frequency/abdominal pain score (risankizumab 180 mg [42.7%] or 360 mg [49.8%]; [withdrawal] placebo [39.0%]), corticosteroid-free clinical remission per Crohn's Disease Activity Index (risankizumab 180 mg [51.0%] or 360 mg [49.5%]; [withdrawal] placebo [40.2%]), and corticosteroid-free endoscopic response (risankizumab 180 mg [44.6%] or 360 mg [44.7%]; [withdrawal] placebo [20.7%]) rates were greater for risankizumab than placebo. Adverse event rates were generally similar,regardless of baseline corticosteroid use. Efficacy of risankizumab 600 mg induction therapy was independent of concomitant corticosteroid use. Risankizumab 180 and 360 mg maintenance therapy yielded high rates of corticosteroid-free clinical and endoscopic outcomes at week 52.

Probiotic Treatment of Ulcerative Colitis with Trichuris Suis Ova: A Randomised, Double-blinded, Placebo-controlled Clinical Trial [the PROCTO Trial

To demonstrate that administration of 7500 Trichuris suis ova [TSO] every second week over 24 weeks would reduce the intestinal inflammation in moderate ulcerative colitis. A single-centre, randomised, double-blinded, placebo-controlled, phase 2b clinical trial of 7500 Trichuris suis ova every 2 weeks for 24 weeks compared with placebo in moderate activity of ulcerative colitis [Mayo score 6-10] were performed. Primary outcome: clinical remission; secondary outcomes: clinical response at 24 weeks, complete corticosteroid-free clinical remission, endoscopic remission, symptomatic remission at 12 and 24 weeks, and partial Mayo score over time. In all, 119 patients were randomised to Trichuris suis ova [n = 60] or placebo [n = 59]. At Week 24, clinical remission was achieved in 30% of Trichuris suis ova-treated vs 34% of placebo-treated (risk ratio [RR] = 0.89; 95% confidence interval [CI]: 0.52-1.50; p = 0.80, intention to treat). No difference was found in clinical response in any of the clinical response subgroups. However, in patients who did not need treatment with corticosteroids during the trial, a temporary effect of TSO was seen in the analysis of symptomatic remission at Week 12 [p = 0.01] and the partial Mayo score at Week 14 and Week 18 [p < 0.05 and p = 0.02]. Compared with placebo, Trichuris suis ova administration was not superior in achieving clinical remission at Week 24 in ulcerative colitis or in achieving clinical Mayo score reduction, complete corticosteroid-free clinical remission, or endoscopic remission. However, Trichuris suis ova treatment induced symptomatic temporary remission at Week 12.

Adaptive Steroid Tapering Impedes Corticosteroid-free Remissions Compared with Forced Tapering in Clinical Trials of Ulcerative Colitis.

It is unclear if steroid tapering protocols can affect clinical trial outcomes in ulcerative colitis [UC], particularly fixed versus adaptive steroid tapering. Fixed steroid tapering involves incremental dose decreases at prespecified intervals, and adaptive steroid tapering uses investigator discretion as determined by the patient's response. In this post-hoc analysis from six clinical trials of UC [VARSITY, ACT 1, PURSUIT, GEMINI1, OCTAVE, and ULTRA2], responders to induction therapy with baseline corticosteroid use were considered as the primary population of interest. Adjustments were made to account for treat-through versus re-randomisation designs, and multivariate regression was performed to account for other potential confounding variables. The primary outcome was corticosteroid-free clinical remission [CR] at 1 year, and secondary outcomes were CR and endoscopic improvement. There was a total of 861 patients who had achieved clinical response after induction and were using corticosteroids. Within multivariate analysis, patients using adaptive steroid tapering regimens were less likely to achieve corticosteroid-free CR at 1 year (odds ratio [OR] 0.66 [95% confidence interval, CI, 0.48-0.92], p = 0.015) but had increased odds for achieving CR at 1 year (OR 1.9 [95% CI 1.43-2.52], p < 0.001). The steroid tapering regimen was not associated with achievement of endoscopic improvement at 1 year. Among patients with UC on corticosteroids in clinical trials, patients using adaptive steroid weaning regimens were less likely to achieve corticosteroid-free CR at 1 year but more likely to achieve CR at 1 year. Consideration should be given to implementing mandatory fixed steroid weaning protocols in future clinical trials of UC.

Tofacitinib in Pediatric Ulcerative Colitis: A Retrospective Multicenter Experience.

Tofacitinib has recently been approved for treatment of moderate-to-severe ulcerative colitis (UC) in adults, yet pediatric data are limited. This international multicenter study describes the effectiveness and safety of tofacitinib in pediatric UC. This is a retrospective review of children diagnosed with UC treated with tofacitinib from 16 pediatric centers internationally. The primary outcome was week 8 corticosteroid-free clinical remission (Pediatric Ulcerative Colitis Activity Index <10). Secondary outcomes were clinical response (≥20-point decrease in Pediatric Ulcerative Colitis Activity Index) at week 8, corticosteroid-free clinical remission at week 24, and colectomy rate and adverse safety events through to last follow-up. The primary outcome was calculated by the intention-to-treat principle. We included 101 children with a mean age at diagnosis of 12.8 ± 2.8 years and a median disease duration of 20 months (interquartile range [IQR], 10-39 months). All had treatment failure with at least 1 biologic agent, and 36 (36%) had treatment failure with 3 agents. Median follow-up was 24 weeks (IQR, 16-54 weeks). Sixteen (16%) children achieved corticosteroid-free clinical remission at week 8, and an additional 30 (30%) demonstrated clinical response. Twenty (23%) of 88 children achieved corticosteroid-free clinical remission at week 24. A total of 25 (25%) children underwent colectomy by median 86 days (IQR, 36-130 days). No serious drug-related adverse events were reported; there was 1 case of herpes zoster and 2 cases of minor blood test perturbations. In this largest real-life pediatric cohort to date, tofacitinib was effective in at least 16% of patients with highly refractory UC by week 8. Adverse events were minor and largely consistent with adult data.

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.

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/characterise other eating disorder cognitive and behavioural symptoms. Participants included adults with UC who are enrolled in an ongoing cohort study with quiescent UC (Simple Clinical Colitis Activity Index [SCCAI] ≤2 or faecal 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 EDE-Q-8 scores. 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 30 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...

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...

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.

Infliximab is an effective option in patients with ulcerative colitis previously exposed to full subcutaneous anti-TNF agent: Results from a real-world multicenter study

BackgroundData on infliximab efficacy in bio-exposed patients with ulcerative colitis (UC) are limited. AimsTo evaluate infliximab effectiveness and its predictors in UC patients with prior exposure to subcutaneous (SC) anti-TNF agent. MethodsIn this multicenter retrospective study (8 centers), we included all consecutive UC patients with prior exposure to subcutaneous anti-TNF, starting infliximab for symptomatic UC, excluding acute severe colitis. Corticosteroid-free clinical remission (CFREM) was assessed at week 14 (W14) and W52 while endoscopic improvement (CFREM + endoscopic Mayo score≤1) was evaluated at W14. ResultsOverall, 104 patients were included (pancolitis=54.8%, primary failure to subcutaneous anti-TNF=57.4%, concomitant immunosuppressant=53.8%, median partial Mayo score at baseline=7[5–8]). The rate of CFREM was 33.6% (35/104) at W14 and 40.4% (42/104) at W52. At W14, endoscopic improvement was achieved in 29.8%(31/104). In multivariable analysis, concomitant immunosuppressant was associated with higher rate of CFREM at W14(OR=2.83[1.06–7.54], p = 0.037) and W52(OR=2.68[1.16–6.22];p = 0.021), while primary failure to a previous subcutaneous anti-TNF agent led to lower rate of CFREM at W14 (OR=0.37[0.14–0.98], p = 0.046). After a median follow-up of 20.9 months[11.7–33.7]), 50.0%(52/104) patients had discontinued infliximab. ConclusionInfliximab is an effective option in UC patients previously exposed to prior subcutaneous anti-TNF agent and should be used with concomitant immunosuppressant.

P689 Adaptive steroid tapering impedes corticosteroid-free remissions compared to forced tapering in UC clinical trials

Abstract Background Protocols for managing steroids in clinical trials of ulcerative colitis (UC) vary. Most trials mandate steroid tapering at the beginning of maintenance phase. Adaptive steroid tapering allows for some discretion on whether to taper steroids for a patient. It remains unclear what impact steroid tapering protocols have on trial outcomes. Methods This post-hoc analysis from many clinical trials of advanced therapies in UC (VARSITY, ACT 1/2, PURSUIT, GEMINI1, OCTAVE and ULTRA2) was carried out under protocols with Vivli (00007656) and YODA (20224882). Responders to induction therapy with baseline corticosteroid use were considered as the primary population of interest. Adjustments were made to account for re-randomization designs and treatment exposure. Univariate analyses were conducted to identify baseline variables that had an association with the primary outcome of interest, one-year corticosteroid-free clinical remission (CR). All covariates with a significant univariate association (p &amp;lt; 0.05) were considered for inclusion in the multivariate model. Logistic regression was used to assess the impact of steroid-weaning regimen on the outcome of interest. Secondary outcome of interest was one-year CR. Results There was a total of 861 patients from the seven included trials who had achieved clinical response after induction and were using corticosteroids. Within multivariate analysis, patients using adaptive steroid weaning regimens were less likely to achieve one year corticosteroid-free CR (odds ratio (OR) 0.66 (95% CI 0.48-0.92), p=0.015). Patients with higher partial Mayo scores were also less likely to achieve one year corticosteroid-free CR (OR 0.88 (95% 0.8-0.97), p=0.012). Other variables found significant on univariate analysis were no longer significant once considered within the multivariate model (smoking, race, albumin, endoscopic Mayo score). For the secondary outcome of one year CR, patients using adaptive steroid weaning regimens had increased odds for achieving one year CR as compared to those using fixed regimens (OR 1.9 (95% 1.43-2.52), p&amp;lt;0.001). Several other variables were also found to have an association with one year CR within the multivariate model (Table 1). Conclusion Among patients with UC on corticosteroids at the time of study enrolment, adaptive steroid weaning regimens were less likely to achieve one-year corticosteroid-free CR but more likely to achieve one-year CR. This may help explain the findings within the VARSITY study, where patients treated with vedolizumab had increased odds for one-year CR but were less likely to achieve one-year corticosteroid-free CR. Consideration should be given to implementing mandatory steroid weaning protocols in future clinical trials of UC.