Higher Rates Of Clinical Remission Research Articles

Risankizumab Concentration but not IL-22 Levels are Associated With Clinical and Biochemical Remission in Patients With Crohn’s Disease

Risankizumab (RZB) is a monoclonal antibody that targets the p19 subunit of interleukin (IL)-23.1 The ADVANCE and MOTIVATE randomized controlled trials (RCTs)2 demonstrated that intravenous (IV) RZB compared with placebo led to higher rates of clinical remission and endoscopic response at week 12 in patients with active Crohn's disease (CD).2 The phase III FORTIFY RCT showed that subcutaneous (SC) RZB was significantly more effective than placebo for achieving clinical remission and endoscopic response as maintenance therapy in patients with moderate-to-severe active CD.3.

Intravenous Versus Subcutaneous Infliximab in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

Subcutaneous (SC) infliximab may provide multiple benefits over intravenous (IV) formulations. However, studies for efficacy and safety in inflammatory bowel disease (IBD) have been constrained by small sizes that limit the interpretation of outcomes, especially for subgroups potentially at high-risk of disease relapse. We conducted a systematic review and random-effects meta-analysis up to January 2023 to evaluate the change in clinical remission after transitioning from IV to SC infliximab in patients with IBD in clinical remission. The primary outcome was measured using the relative risk for meta-analysis. 15 studies of patients established ≥3 months on IV infliximab were identified, consisting of 1371 patients and 840 patient-years of follow-up. There was no loss of clinical remission in the IBD cohort overall, Crohn's disease (CD), and perianal CD p=0.55 & p=0.11 at 9-12 months, and p=0.50 at 6 months respectively). Neither prior IV dose (≤10mg/kg 6-weekly) (p=0.48) nor IBD disease subtype was associated with an increased clinical relapse rate at 6 months (p=0.48 and p=0.45 (UC vs CD), respectively). Changing patients established on IV infliximab to an SC formulation is associated with a high ongoing clinical remission and low adverse event rate. Furthermore, there are no signals for adverse outcomes among different IBD disease subtypes, nor in those on escalated IV infliximab dosing schedules up to 10mg/kg 6-weekly. This data should provide patients and clinicians alike with confidence in SC infliximab use in IBD.

Efficacy of the Craniopharyngioma Resection via Expanded Endoscopic Endonasal Transsphenoidal Approach in the Treatment of Complex Craniopharyngioma and Its Effect on Pituitary Function and Complications of Patients.

Surgical resection is the most effective method for craniopharyngioma, with complex operations and a high incidence of complications, especially for complex craniopharyngioma. The study focuses on selecting a proper surgical method to treat complex craniopharyngioma. A clinical study was conducted in this direction to explore the efficacy of expanded endoscopic endonasal transsphenoidal approach (EETS) and transcranial approach (TCA) in the treatment of complex craniopharyngioma and their effects on pituitary function and complications of patients. The clinical data of 73 patients with complex craniopharyngioma in Baoding No.2 Central Hospital from December 2017 to December 2022 were retrospectively analyzed. 13 patients who did not meet the admission criteria were excluded, and 60 patients were finally included. The included patients were divided into the TCA and EETS groups according to the treatment method. The surgical conditions, total tumor resection rate, clinical remission rate, and complications of patients in two groups were compared. The pituitary function of all patients, including thyroid stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), and human growth hormone (hGH), was compared. A total of 60 patients were finally included in the study, including 30 cases in the EETS group and 30 cases in the TCA group. The two groups had no statistical difference in baseline demographic characteristics and pathological types (p > 0.05). Compared with the TCA group, the EETS group had less intraoperative blood loss, operation time, tumor resection time, and hospitalization time (p < 0.001) and had a significantly higher total tumor resection rate and clinical remission rate (p < 0.05). The EETS group had higher ACTH and hGH levels than the TCA group (p < 0.05). There was no statistical difference between the two groups incidence of complications and disease recurrence rate (p > 0.05). The craniopharyngioma resection via EETS has a significant therapeutic effect in complex craniopharyngioma with a high total tumor resection rate and clinical remission rate, which can protect the pituitary function of patients and provide more benefits for patients.

Herbal Medicines for the Treatment of Active Ulcerative Colitis: A Systematic Review and Meta-Analysis.

Herbal medicines are used by patients with IBD despite limited evidence. We present a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating treatment with herbal medicines in active ulcerative colitis (UC). A search query designed by a library informationist was used to identify potential articles for inclusion. Articles were screened and data were extracted by at least two investigators. Outcomes of interest included clinical response, clinical remission, endoscopic response, endoscopic remission, and safety. We identified 28 RCTs for 18 herbs. In pooled analyses, when compared with placebo, clinical response rates were significantly higher for Indigo naturalis (IN) (RR 3.70, 95% CI 1.97-6.95), but not for Curcuma longa (CL) (RR 1.60, 95% CI 0.99-2.58) or Andrographis paniculata (AP) (RR 0.95, 95% CI 0.71-1.26). There was a significantly higher rate of clinical remission for CL (RR 2.58, 95% CI 1.18-5.63), but not for AP (RR 1.31, 95% CI 0.86-2.01). Higher rates of endoscopic response (RR 1.56, 95% CI 1.08-2.26) and remission (RR 19.37, 95% CI 2.71-138.42) were significant for CL. CL has evidence supporting its use as an adjuvant therapy in active UC. Research with larger scale and well-designed RCTs, manufacturing regulations, and education are needed.

Upadacitinib Achieves Clinical and Endoscopic Outcomes in Crohn’s Disease Regardless of Prior Biologic Exposure

Upadacitinib, an oral Janus kinase inhibitor, achieved significantly higher rates of clinical remission and endoscopic response vs placebo during induction (U-EXCEL [NCT03345849]; U-EXCEED [NCT03345836]) and maintenance (U-ENDURE [NCT03345823]) treatment in patients with moderate-to-severe Crohn's disease (CD). Prior biologic failure is often associated with reduced responses to subsequent therapies. This post hoc analysis assessed upadacitinib efficacy by prior biologic failure status. Patients were randomized to placebo or upadacitinib 45 mg (UPA45) for 12 weeks (induction). UPA45 clinical responders were enrolled in U-ENDURE and rerandomized to placebo, upadacitinib 15 mg (UPA15), or upadacitinib 30 mg (UPA30) for 52 weeks. Assessments were by prior biologic failure. Of 1021 patients, 733 (71.8%) had prior biologic failure. Across outcomes and subgroups, upadacitinib-treated patients achieved higher rates vs placebo. During induction, upadacitinib had higher rates vs placebo for clinical remission based on stool frequency/abdominal pain score (without failure: 54.0% vs 28.3%; with failure: 42.2% vs 14.1%) and endoscopic response (without failure: 52.0% vs 16.2%; with failure: 35.7% vs 5.3%). In maintenance, the greatest treatment effect (upadacitinib vs placebo) was among patients with prior biologic failure treated with UPA30 (clinical remission without failure: 58.5% vs 32.7%; with failure: 42.5% vs 8.7%; endoscopic response without failure: 43.9% vs 17.9%; with failure: 38.9% vs 4.0%). Patients without vs with prior biologic failure had fewer adverse events. Upadacitinib led to higher absolutes rates of clinical and endoscopic outcomes in patients without vs with prior biologic failure. Patients treated with upadacitinib achieved greater rates of clinical and endoscopic improvements vs placebo, regardless of prior biologic exposure. GOV: NCT03345849, NCT03345836, NCT03345823.

Evidence-Based Approach to Chronic Antibiotic Refractory Pouchitis: A Review.

Chronic antibiotic refractory pouchitis after restorative proctocolectomy with IPAA, characterized by at least 4 weeks of pouchitis symptoms that have not responded to standard antibiotic therapy, presents a therapeutic challenge for patients and health care providers. The aim of this narrative review was to summarize the current evidence regarding the management of chronic antibiotic refractory pouchitis. Studies were identified through a search of the PubMed database from the National Library of Medicine. We included case series, cohort studies, randomized controlled trials, and systematic reviews with meta-analyses that addressed chronic antibiotic refractory pouchitis management, with prioritization of data published within the past 3 to 5 years. Studies examining pharmacologic and select nonpharmacologic interventions were included. Outcomes measures included clinical, endoscopic, and histologic end points. Mesalamine has demonstrated efficacy in symptom improvement but no improvement in quality of life. Budesonide has demonstrated high rates of clinical remission that have mostly been sustained in a small number of patients. Anti-tumor necrosis factor therapies have demonstrated efficacy in reaching clinical and even endoscopic end points, although rates of treatment discontinuation were not insignificant. Limited evidence is encouraging for the use of ustekinumab in achieving clinical response. Data for vedolizumab are favorable across clinical, endoscopic, and histologic end points, including one of the only randomized, placebo-controlled trials. Nonmedication therapies, including hyperbaric oxygen therapy and fecal microbiota transplant, have undergone limited evaluation, and concerns about the ultimate accessibility of these therapies remain. Overall, studies assessing therapeutic options for chronic antibiotic refractory pouchitis are mostly limited to case series and retrospective studies with small sample sizes. Biologic therapies have demonstrated efficacy in the management of chronic antibiotic refractory pouchitis and offer a steroid-sparing option for refractory disease. Nonpharmacologic therapies, including hyperbaric oxygen and fecal microbiota transplant, require further exploration. See video from symposium .

Real-world experience of vedolizumab use in Colombian patients with inflammatory bowel disease—EXVEDOCOL

BackgroundReal-world studies about the effectiveness and safety of vedolizumab (VDZ) in the treatment of inflammatory bowel disease (IBD) in Latin America are scarce. Our study describes the effectiveness and safety of VDZ in Colombian patients with IBD. MethodsEXVEDOCOL (EXperience of VEDOlizumab in COLombia) was a retrospective, multicenter, observational study. Adults with IBD receiving a first dose of VDZ between July 2016 and October 2018 were included. The co-primary outcomes clinical response, and remission, were determined at week 14 and last visit during the maintenance phase (LVMP). The secondary outcomes, deep remission and loss of response were recorded at LVMP. ResultsThirty-one patients (25 ulcerative colitis (UC), 6 Crohn's disease (CD)) were included. At week 14, clinical response was achieved by 87.1% (27/31) of the patients treated with VDZ, while loss of response was reported in 6.7% (2/30). The remission rate at week 14 was 65.5% (19/29) and 75.9% (22/29) at LVMP. Prior anti-TNF exposure was reported in 61.3% (19 patients) of whom 84.2% (16/19) achieved clinical response at week 14 and 89.5% (17/19) at LVMP. For anti-TNF naïve patients, clinical response was recorded in 91.7% (11/12) at week 14 and 100% (12/12) at LVMP. ConclusionsHigh clinical remission rates and safety profile highlight VDZ as a valuable treatment option for IBD patients. Anti-TNF naïve patients may derive greater benefit from therapy. Studies with larger cohorts could confirm these findings.

P922 A multicenter retrospective real-world study to determine the optimal cases of vedolizumab-treated UC patients

Abstract Background Vedolizumab (VDZ) is a gut-selective monoclonal antibody approved for ulcerative colitis (UC). This real-world study aimed to evaluate the effectiveness of VDZ in the treatment of UC, with the goal of further treatment optimization. Methods In this multicenter, retrospective, observational chart review, 370 patients with UC who received at least one dose of VDZ in clinical practice at 16 tertiary hospitals in Japan were enrolled. Comprehensive analyses of predictors of 2- and 54-week remission, drug persistence, and the development of loss of response were performed. Results Lower partial Mayo scores and lower Mayo endoscopic subscores were significantly associated with 2-week remission in the multivariate analysis. More 2-week remitters achieved clinical remission at Week 52 than non-2-week remitters. Clinical remission rates were significantly higher in biologic-naïve than in biologic-non-naïve patients across Weeks 2 to 54. Higher clinical remission rates at Week 54 were significantly associated with lower baseline disease severity and no prior anti-tumor necrosis factor alpha (anti- TNFα) treatment. Among patients with prior anti-TNFα treatment, longer duration of anti-TNFα treatment was associated with higher clinical remission rates at Week 54 (28.1%, 32.7%, and 60.0% for ≤3 months, &amp;gt;3 to &amp;lt;12 months, and ≥12 months, respectively, p=0.001 between groups). In addition, clinical remission rate at Week 54 was higher in patients who had loss of response to anti-TNFα treatment than in those who had primary nonresponse (54.4% vs 24.6%; p=0.001). The 54-week persistence rate was 64.5%. Concomitant use of tacrolimus (OR 2.76, 95% CI 1.00, 7.62, p=0.05) and shorter disease duration (median:7.8 years), (OR 0.33, 95% CI 0.13, 0.82 for ≥7.8 years vs &amp;lt;7.8 years p=0.017) were associated with loss of response to VDZ in the multivariate analysis, but prior use of anti- TNFα treatment was not. Conclusion This retrospective study confirms favorable outcomes with VDZ in patients without prior exposure to anti-TNFα treatment. However, among patients with history of anti-TNFα- exposure, better outcomes were observed among those who experienced loss of response than those with primary nonresponse, as well as those who had a longer duration of anti-TNFα treatment.

OP06 Risankizumab Maintenance Therapy in Patients With Moderately to Severely Active Ulcerative Colitis: Efficacy and Safety in the Randomised Phase 3 COMMAND Study

Abstract Background Risankizumab (RZB), a monoclonal antibody targeting interleukin-23 p19, was evaluated for maintenance therapy in patients with moderately to severely active ulcerative colitis (UC) and clinical response to RZB intravenous (IV) induction treatment in a phase 3 double-blind, placebo (PBO)-controlled withdrawal (WD) maintenance study, COMMAND (NCT03398135). Methods Patients with moderately to severely active UC who achieved a clinical response per Adapted Mayo score after 12 or 24 weeks (wks) of RZB IV treatment in the phase 2b and phase 3 INSPIRE induction studies (NCT03398148)1 were randomized 1:1:1 in COMMAND to RZB 180 mg (RZB180), 360 mg (RZB360), or PBO (RZB withdrawal) subcutaneous (SC) treatment every 8 wks for 52 wks. The efficacy analysis included responders to 12 wk of RZB IV, while the safety analysis included responders to 12 or 24 wk of RZB IV. The primary endpoint was clinical remission per Adapted Mayo score at wk 52. Key secondary endpoints included endoscopic improvement, HEMI, endoscopic remission, steroid-free clinical remission, maintenance of clinical remission, no bowel urgency, and no abdominal pain at wk 52. Results At baseline of induction, demographics and disease characteristics were similar between treatment groups; 75% of 548 patients had history of inadequate response or intolerance to ≥ 1 advanced therapy (AT). Patients receiving RZB180 (40.2%) and RZB360 (37.6%) achieved significantly higher rates of clinical remission vs WD (25.1%) (adjusted treatment difference vs WD: 16.3% and 14.2%, respectively; P ≤ .01) (Fig. 1A). Greater proportions of patients achieved endoscopic improvement, HEMI, endoscopic remission, steroid-free clinical remission, maintenance of clinical remission, no bowel urgency, and no abdominal pain with RZB180 and RZB360 vs WD (Fig. 1B). The overall rates of adverse events (AEs), and serious infections were similar among treatment groups (Table 1). Serious (presented as events/100 patient-years [E/100 PY]) (RZB180: 5.9; RZB360: 6.3; WD: 11.4) and severe AEs (RZB180: 1.6; RZB360: 4.0; WD: 8.0) were lower in the RZB arms vs WD. No active tuberculosis, adjudicated anaphylaxis, serious hypersensitivity, or adjudicated major adverse cardiovascular events were reported in any treatment group. Conclusion In patients with moderately to severely active UC responding to 12-week RZB induction therapy, RZB maintenance dosing with 180 mg and 360 mg SC was superior to placebo in achieving clinical remission as well as other key clinical, endoscopic, and histological-endoscopic endpoints. RZB was well-tolerated, with no new safety concerns observed.

P919 Crohn’s Disease Exclusion Diet as add-on therapy in refractory pediatric patients

Abstract Background Despite the accumulating body of evidence of the efficacy and tolerability of Crohn’s disease exclusion diet (CDED) combined with partial enteral nutrition (PEN), there is still a paucity data regarding its use in combination with other medical treatments. We aimed at assessing its efficacy in re-inducing remission in pediatric CD patients experiencing disease relapse while on other maintenance therapies. Methods This was a single-center, retrospective, observational study conducted at an Italian national referral pediatric IBD center. Incident patients who received CDED coupled with PEN in the setting of the loss of response to other maintenance therapies from January 1st, 2020 to June 30th 2023 were included. Clinical remission at the end of each phase was defined by a weighted Pediatric Crohn’s Disease Activity Index (wPCDAI) below 12.5. Biochemical remission was defined by a c-reactive protein (CRP) lower than 0.5 mg/dL. A FC lower than 150 mg/kg was used as a surrogate of mucosal improvement (MI). Results 25 patients (52% males) met inclusion criteria and were included in the analysis. Median disease duration at CDED+PEN initiation was 31 months (Q1-Q3: 8.4-13.8). The most frequent disease location was ileocolonic (64%), 3 (12%) patients had isolated colonic involvement. 9 (36%) patients had stricturing/penetrating phenotype. 16 patients (68%) were being treated with an anti-TNF-alpha agent, whereas 5 (20%) patients were receiving ustekinumab (Table 1). wPCDAI, CRP and FC significantly decreased after the firs 8 weeks of treatment (22.5 vs 2.5, 1 vs 0.2, 640 vs 360, p&amp;lt;0.001, p=0.019 and p=0.007, respectively). At the end of phase I, 19/25 (76%) of the patients achieved clinical remission, 15 (60%) patients had CRP levels within normal range and 7 (28%) of them had normalized FC. 18/25 patients (72%) had received Exclusive Enteral Nutrition (EEN) for the induction of remission at diagnosis. Patients who achieved clinical remission with the EEN course (i.e.: a wPCDAI of &amp;lt; 12.5 after a complete course of EEN) were more likely to achieve clinical remission when receiving CDED + PEN (11/13 vs 1/5, p=0.022). Conclusion CDED coupled with PEN is a valid treatment strategy in the setting of secondary loss of response to maintenance treatments in children with CD. A previous successful course of EEN was associated with higher rates of clinical remission at the end of phase I, thereby possibly identifying a subset of “nutritional responder” patients.

DOP54 Guselkumab and golimumab combination induction therapy in Ulcerative Colitis results in early local tissue healing that is sustained through guselkumab maintenance therapy

Abstract Background Combination induction therapy with guselkumab (GUS), an interleukin (IL)-23p19 subunit antagonist, and golimumab (GOL), a tumor necrosis factor (TNFα) antagonist, induced higher rates of clinical remission, endoscopic, and histologic outcomes than either monotherapy at Week (WK)12 in patients (pts) with ulcerative colitis (VEGA NCT03662542). Data through WK38 suggested the continued benefit of combination induction even after a transition to GUS monotherapy at WK12. We explored early molecular changes in colon tissue in a subset of pts at WK4 to define mechanistic contributions of each monotherapy and combination; these parameters were evaluated again at WK38 to assess potential carry-over of efficacy. Methods Colon biopsies were obtained at baseline (n=195), WK4 (n=42 substudy), and WK38 (n=172). Transcriptional profiles were generated with RNA sequencing (RNAseq). Gene correlation network analysis was applied in conjunction with publicly available single cell RNAseq data to define biologically relevant bulk and cell type-specific transcriptional modules associated with molecular features of disease. Gene set variation analysis (GSVA) was used to quantitatively assess changes in biologic modules with treatment. Results At WK4, combination induction (n=10) showed significant (p&amp;lt;0.05) decreases in molecular features compared to GUS (n=19) and GOL (n=13), including transcriptomic modules representing the IL-23 pathway, interferon response, and inflammatory epithelial and myeloid transcriptional states associated with endoscopic improvement at WK4 (Mayo endoscopy subscore of 0 or 1) (combination 5/11, GOL 1/13; GUS 2/19). Reduction (p&amp;lt;0.05) in inflammatory modules persisted through WK38 with combination vs monotherapy induction. Module changes between treatments at WK4 indicated a stronger correlation between GUS and combination (R=0.8; p=2.2e-16) than GOL and combination (R=0.52; p=4.1e-12), with processes associated with epithelial and stromal biology, and mucosal inflammation. In contrast, the combination effect on specific neutrophil/myeloid biology at WK4 was more similar to GOL than GUS, supporting the early role of GOL in targeting innate inflammation. Conclusion Combination induction with GUS and GOL showed significant reductions in major inflammatory features of disease as early as WK4 which persisted through WK38 with GUS maintenance. Correlative analysis supports the role of GUS as the primary driver of tissue healing, with GOL further contributing to innate inflammatory activity, which demonstrate differential and complementary mechanisms of action of TNFα and IL-23p19 subunit blockade.

P960 Comparison of clinical outcomes by induction therapy response status in patients with Inflammatory Bowel Disease (IBD) treated with subcutaneous (SC) versus intravenous (IV) infliximab (IFX): Post hoc analysis of a pivotal, randomised controlled trial

Abstract Background Clinical associations between initial response and long-term outcome are well established for IV IFX in IBD.1,2 In 2020, SC IFX was approved in Europe for treating moderate-to-severe Crohn’s disease (CD) or ulcerative colitis (UC), based on a pivotal randomised trial (NCT02883452) comparing SC and IV IFX.3 This post hoc analysis investigated clinical outcomes in patients (pts) treated with SC or IV IFX, by response to IV IFX induction. Methods In the pivotal trial, adults with active CD or UC received IV IFX induction (5 mg/kg; Week [W] 0 and W2), before randomisation to SC (n=66) or IV (n=65) arms. W6 clinical response (≥70-point decrease in Crohn’s Disease Activity Index [CDAI] score [CD]; ≥2-point decrease in partial Mayo score with ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding subscore of 0 or 1 [UC]) was a stratification factor. The SC arm received SC IFX (120/240 mg for pts weighing &amp;lt;80/≥80 kg) every 2 weeks from W6–54; the IV arm received IV IFX 5 mg/kg every 8 weeks (W6–22), then switched to SC IFX (W30–54). Rates of clinical remission (CDAI score &amp;lt;150 [CD]; partial Mayo score ≤1 [UC]) and trough IFX concentrations (Ctrough) were assessed at W6, W30 and W54. Analyses were descriptive. Results There were 101 induction responders (IRs) to IV IFX, who were randomised to the SC arm (n=49, 74.2%; SC-IR subset) or the IV arm (n=52, 80.0%; IV-IR subset). Correspondingly, there were 17 (25.8%) and 13 (20.0%) induction non-responders (INRs; SC-INR and IV-INR subsets, respectively). In both study arms, IRs had higher clinical remission rates than INRs at both W30 and W54 (Figure A). Comparing by formulation, the SC-INR subset had nearly twice the W30 clinical remission rate of the IV-INR subset (58.8% vs. 30.8%; p=0.159 [Fisher exact test]). In addition, IV-INR subset clinical remission rates numerically increased after pts switched to SC IFX (W30: 30.8% vs. W54: 46.2%; p=0.476 [McNemar test]). These observations were generally consistent with Ctrough findings (Figure B); median Ctrough in the IV-INR subset increased from 1.5 to 18.3 µg/mL (p=0.005 [Wilcoxon signe-drank test]) after switching to SC IFX. Conclusion Findings suggested associations between initial response to IFX induction therapy and positive long-term outcomes for both SC and IV IFX, and supported potential benefits with SC IFX maintenance therapy for INRs, compared with the option of IV IFX maintenance. Given the post hoc nature of the analysis and the small analysis population (thus statistical inconclusiveness), investigation in larger studies is warranted. 1Murthy SK et al. Inflamm Bowel Dis 2015;21:2090–6. 2Wong ECL et al. J Crohns Colitis 2021;15:1114–9. 3Schreiber S et al. Gastroenterology 2021;160:2340–53.

Inflammatory mesenteric fat detected by Intestinal ultrasound is correlated with poor long-term clinical outcomes in patients with Crohn's disease

BackgroundData on the correlation between inflammatory mesenteric fat (i-fat), detected by intestinal ultrasound (IUS), and the prognosis of Crohn's disease (CD) remains limited. AimsTo investigate the impact of IUS-detected i-fat on long-term clinical outcomes. MethodsWe retrospectively enrolled 171 active CD patients who initiated infliximab. Clinical remission (CR), mucosal healing (MH) and transmural healing (TH) were assessed at week-14 and 1 year. ResultsBaseline i-fat was detected in 107 patients, while 64 without i-fat. At week-14 and 1 year, patients with i-fat showed lower rates of CR (61.7% vs. 87.5%; 62.3% vs. 86.7%), MH (20.6% vs. 46.9%; 38.6% vs. 65.0%) and TH (10.3% vs. 31.3%; 21.6% vs. 51.7%), compared to those without (all p<0.01). Multivariable analysis revealed that baseline i-fat was a negative predictor for CR (OR=0.212) and MH (OR=0.425) at week-14, and CR (OR=0.340) and TH (OR=0.364) at 1 year (all p<0.05). At week-14, 56 patients with baseline i-fat recovered to without i-fat. Patients with i-fat recovery had higher rates of CR (86.8% vs. 23.1%), MH (58.5% vs. 7.7%) and TH (34.0% vs. 2.6%) at 1 year than those with i-fat at week-14 (all p<0.001). ConclusionIUS-detected i-fat correlated poor long-term clinical outcomes in CD with infliximab.

Efficacy of early biologic therapy versus late/conventional therapy in children and adolescents with Crohn's disease: A systematic review and meta-analysis.

The objective of this study was to estimate the effectiveness of early biologics compared to conventional treatment in the management of Crohn's disease among pediatric and adolescent patients. A comprehensive literature search was conducted in four electronic databases to identify relevant studies published from inception to 2023. The inclusion criteria comprised randomized controlled trials (RCTs) and cohort studies that reported on the efficacy and clinical outcomes of early biologic therapy compared to late/conventional therapy in children with Crohn's disease. The quality of the studies was assessed using the Cochrane Risk of Bias tool and the Newcastle Ottawa scale. A total of 13 studies (2 RCTs and 11 cohort studies), involving 861 patients, were included in the meta-analysis. The results demonstrated that early biologic therapy was associated with a significantly higher rate of clinical remission (risk ratio [RR] 1.30, 95% confidence interval [CI] 1.10-1.54), lower relapse rates (RR 0.33, 95% CI 0.21-0.53), and improved mucosal healing (RR 1.47, 95% CI 1.10-1.97) compared to late/conventional therapy. However, it should be noted that there was evidence of publication bias among studies reporting clinical remission. In conclusion, early biologic therapy is significantly more effective in achieving clinical remission (within two years of diagnosis), promoting mucosal healing, and reducing relapse rates in pediatric and adolescent patients with Crohn's disease, compared to late/conventional therapy. These findings emphasize the importance of initiating biological therapy early in the treatment of Crohn's disease in this patient population.

Dual-Targeted Therapy in Pediatric Inflammatory Bowel Disease: A Comprehensive Review.

Inflammatory bowel disease (IBD) is a chronic systemic immune-mediated disorder. The disease is triggered and perpetuated by a complex interplay between genetic predisposition, dysregulated immune responses, and environmental factors. Pediatric IBD is considered to be more aggressive compared with adult-onset IBD, and commonly requires more intensive pharmacological and surgical treatments. Although the use of targeted therapy, such as biologic therapy and small molecule therapy, is on the rise, there are children with IBD who are refractory to all current therapeutic options. For them, a combination of biologic agents or a biologic agent with small molecules as dual-targeted therapy (DTT) may be a possible therapeutic option. The main indications for DTT are high inflammatory burden and refractoriness to standard therapy, extra-intestinal manifestations of IBD, adverse effects of therapy, and co-existing immune-mediated inflammatory disorders. Several combination therapies were described for pediatric refractory IBD. The main ones were anti-tumor necrosis factor (TNF) agents and vedolizumab (VDZ), anti-TNF and ustekinumab (UST), VDZ and UST, and biologic agents with tofacitinib. DTT exhibits high efficacy, with high rates of clinical response and remission as well as biomarker remission. The data on endoscopic and radiologic remission are scarce. Most of the adverse effects reported under DTT were mild; however, the serious ones that had been observed mandate a profoundly cautious approach when considering it. Triple immunosuppressive therapy and combinations of biologics with emergent therapies such as selective Janus kinase inhibitors, sphingosine-1-phosphate receptor modulators, and anti-interleukin-23 agents, are potential future regimens for children with IBD who are refractory to current therapeutic options. This review provides an update of publications on these issues.

Early intervention with biologic therapy in Crohn´s disease: how early is early?

Early biologic therapy within the first 18-24 months after diagnosis is associated with improved clinical outcomes in Crohn's disease [CD]. However, the definition of the best time to initiate biologic therapy remains unclear. We aimed to assess if there is an optimal timing for early biologic therapy initiation. This was a multicentre retrospective cohort study including newly diagnosed CD patients who started anti-tumour necrosis factor [TNF] therapy within 24 months from diagnosis. The timing of initiation of biologic therapy was categorised as ≤6, 7-12, 13-18, and 19-24 months. The primary outcome was CD-related complications defined as a composite of progression of Montreal disease behaviour, CD-related hospitalisations, or CD-related intestinal surgeries. Secondary outcomes included clinical, laboratory, endoscopic, and transmural remission. We included 141 patients where 54%, 26%, 11%, and 9% started biologic therapy at ≤6, 7-12, 13-18, and 19-24 months after diagnosis, respectively. A total of 34 patients [24%] reached the primary outcome: 8% had progression of disease behaviour, 15% were hospitalised, and 9% required surgery. There was no difference in the time to a CD-related complication according to the time of initiation of biologic therapy within the first 24 months. Clinical, endoscopic, and transmural remission was achieved in 85%, 50%, and 29%, respectively, but no differences were found according to the time of initiation of biologic therapy. Starting anti-TNF therapy within the first 24 months after diagnosis was associated with a low rate of CD-related complications and high rates of clinical and endoscopic remission, although we found no differences with earlier initiation within this window of opportunity.

The Efficacy of Currently Licensed Biologics for Treatment of Ulcerative Colitis: A Literature Review.

Biologics have been emerging as promising therapies in ulcerative colitis (UC) patients who are refractory to conventional medical treatment. This literature review aims to appraise the existing evidence on the efficacy and safety of NICE approved biological therapies, of which there are currently five licensed drugs, available for the treatment of UC in adults. An initial search was performed using National Institute of Clinical Excellence (NICE) guidelines. A further literature search of EMBASE, MEDLINE, Science Direct and Cochrane Library databases was done, resulting in a total of 62 studies being included in this review. Recent and seminal papers were included. Inclusion criteria for this review were adult participants and English papers only. In most studies, anti-tumour necrosis factorɑ (TNFɑ) naïve patients were found to have improved clinical outcomes. Infliximab was found to be highly effective in inducing short-term clinical response, clinical remission as well as mucosal healing. However, loss of response was common and dose escalation was often required for achievement of long-term efficacy. Adalimumab was found to have both short-term and long-term efficacy which was also supported by real-world data. Golimumab was shown to have comparable efficacy and safety profiles to other biologics, although lack of therapeutic dose monitoring and loss of response is a barrier to optimising golimumab treatment efficacy. Vedolizumab was shown to have higher clinical remission rates when compared to adalimumab in a head-to-head trial, and the most cost-effective biologic when calculating quality-adjusted life years. Ustekinumab was found to significantly improve clinical remission rates in UC patients who were previously unresponsive to other biological treatments. However, as this is a newly licensed drug, there is limited literature currently available. Further, head-to-head studies are required to help determine the optimal treatment for patients with UC. With patents expiring, the development of biosimilars will help to reduce costs and increase the availability of these drugs to patients.

The Impact of Confounders on Symptom-Endoscopic Discordances in Crohn's Disease.

Discordances between clinical and endoscopic Crohn's disease (CD) activity indices negatively impact the utility of clinic visits and efficacy assessments in clinical trials. Bile acid diarrhea (BAD) and small intestinal bacterial overgrowth (SIBO) mimic CD symptoms. This study quantified the impact of BAD and SIBO on the relationship between clinical and endoscopic disease activity indices. CD patients with 7α-hydroxy-4-cholesten-3-one (7C4) serum measurements and/or SIBO breath tests and matched clinical and endoscopic scores were included. Clinical remission (stool frequency [SF] ≤ 1 and abdominal pain score ≤ 1) rates were compared between those with and without (1) endoscopic remission, (2) BAD (7C4 > 55 ng/mL), and (3) SIBO. Of 295 CD patients, 219 had SIBO testing and 87 had 7C4 testing. Patients with elevated 7C4 had lower proportions with clinical remission (14% vs 40%, P = .007) and SF ≤ 1 (14% vs 42%, P = .004) compared to those with normal 7C4. In patients with normal 7C4, higher rates of clinical remission (65% vs 27%, P = .01) and SF ≤ 1 (71% vs 27%, P = .003) existed in patients with endoscopic remission compared to those without endoscopic remission. Conversely, among the entire 295 patient cohorts, nearly identical clinical remission rates existed between those with and without endoscopic remission (25% vs 24%, P = .8), and the Crohn's Disease Patient-Reported Outcome-2 score was not accurate for predicting endoscopic remission (Area Under the Curve (AUC): 0.48; 95% CI, 0.42-0.55). SIBO status did not impact clinical remission rates (P = 1.0). BAD, but not SIBO, contributed to symptom scores. A relationship between endoscopic inflammation and clinical remission rates only existed in patients without 7C4 elevations.

Effectiveness and Safety of Vedolizumab in Inflammatory Bowel Disease: A Comprehensive Meta-analysis of Observational Studies.

Many observational studies on the use of vedolizumab [VDZ] in patients with Crohn's disease [CD] and ulcerative colitis [UC] have been published in the past few years. We aimed to comprehensively summarise its effectiveness and safety by pooling data only from observational studies. PubMed/Medline and Embase were systematically searched for observational studies on patients with CD and UC treated with VDZ through December 2021. The rates of clinical remission and overall adverse events were the primary outcomes. The rates of steroid-free clinical remission, clinical response, mucosal healing, C-reactive protein normalisation, loss of response, VDZ dose escalation, colectomy, serious adverse events, infections, and malignancies were considered as secondary outcomes. In all, 88 studies comprising 25 678 patients [13 663 with CD and 12 015 with UC] met the inclusion criteria. In patients with CD, the pooled estimate rates of clinical remission were 36% at induction and 39% at maintenance. In patients with UC, the pooled estimate rates of clinical remission were 40% at induction and 45% at maintenance. The pooled estimate of incidence rate of adverse events was 34.6 per 100 person-years. At multivariable meta-regression analysis, studies with increased male proportion were independently associated with higher rates of clinical remission and steroid-free clinical remission at both induction and maintenance, and clinical response at maintenance in patients with CD. Studies with increased disease duration were independently associated with higher mucosal healing rates at maintenance in patients with UC. Observational studies demonstrated extensively the effectiveness of VDZ, with a reassuring safety profile.

P722 Symptom-based disease trajectories Identify a population of early super-responders in ulcerative colitis achieving complete disease control under targeted therapy

Abstract Background Clinical trials with advanced therapies typically document the efficacy of induction and maintenance therapies as landmark endpoints. In ulcerative colitis (UC), independent assessments of clinical remission, endoscopic improvement, inflammatory biomarker, and histologic response are used, while little is known about the individual patient benefit. Disease control (DC) as a composite of symptomatic, biochemical, and morphologic remission becomes important to achieve for patients. By analysing their symptom trajectories towards the new outcome DC, distinct subpopulations of the seemingly uniform therapy response phenotype in UC can be identified. In a prospective cohort, we investigate UC patients using symptoms (i.e., partial Mayo Clinical Score (PCMS)) to detect different trajectories that may lead to DC. Methods 231 UC patients from Kiel Campus of University Hospital Schleswig-Holstein receiving first time induction and maintenance therapy with anti-TNF, anti-IL-12/23, anti-Integrin or JAK inhibitors (JAKi) between 2010-2022 were enrolled. Patients were assigned by clinical choice to their therapy and received standard care: Symptoms were assessed by PCMS with laboratory investigations at each visit (every 4-12 weeks) and endoscopies (at week 0, 14, 52) were evaluated using Mayo endoscopic score (eMayo) and histology assessment with Nancy index (NI). We defined DC at week 52 (DC52) as the combination of eMayo =0, NI =0-1, PMCS =0-1, C-reactive protein &amp;lt;5 mg/l and leucocyte counts 2.5-12/nl. We performed ANOVA and unpaired Wilcoxon tests at each timepoint as well as ROC analyses to identify thresholds discriminating different trajectories. Results 24.2% (56) of patients achieved DC52, while 25.6% (59) reached week 52 without DC and 50.2% (116) changed therapy within 52 weeks due to inefficacy. We identified an early separation of PMCS trajectories between DC52 (2.07, ±0.27SEM) vs. non-DC52 (3.49, ±0.27SEM) already 6 weeks after induction (p &amp;lt;0.001; Figure 1&amp;2). At week 6, PMCS ≤2 (41.76% vs. 14.06%; sensitivity 0.47, specificity 0.76) and PMCS change from baseline &amp;gt;3 (40.24% vs. 16.92%; sensitivity 0.79, specificity 0.60) were associated with higher rates of DC52 vs. non-DC52. Linking DC52 with prospective outcomes, we observed higher rates of clinical remission (75.00% vs. 27.12%) and DC at week 104 (57.14% vs. 20.34%) in DC52 vs. non-DC52. Conclusion In this real-world cohort, DC52 was characterized by early drop of PMCS and a higher likelihood of DC until week 104. While our results await replication, the observation of discrete super-response trajectories leading to DC could give rise to algorithmic trials investigating early change of therapy for patients not joining an ideal trajectory as early as week 6.