Severe Crohn's Disease Research Articles

Protocol for a first-in-human feasibility study of T regulatory cells (TR004) for inflammatory bowel disease using (ex vivo) Treg expansion (TRIBUTE).

Crohn's disease (CD) is a chronic, immune-mediated inflammatory bowel disease (IBD), presenting with symptoms of abdominal pain and bleeding from the gastrointestinal tract. There is no known cure. In vitro-expanded 'thymus-derived' regulatory T cells (tTreg) have shown promise in preclinical models of IBD, leading to interest in their use as a potential therapy in CD. We present a study protocol for a first-in-human study of Tregs for IBD using ex vivo Treg expansion. This study will explore the preliminary safety and tolerability of a single dose of Treg immunotherapy and will inform the design of a subsequent larger trial. Four patients will be recruited from gastroenterology clinics at Guy's and St Thomas' NHS Foundation Trust. Eligible participants are those who are at least 18 years old, have a diagnosis of active moderate to severe CD and have failed to respond to or tolerate at least two prior lines of standard medication. Participants receive a single dose of autologous ex vivo-expanded Tregs and will be followed up to week 21 to collect safety and exploratory efficacy data. Additional safety monitoring will occur at 1 and 2 years post-dose. The primary endpoint is defined as the occurrence of dose-limiting toxicity occurring within 5 weeks post-infusion. The study protocol and related documents have been approved by a NHS Research Ethics Committee, the Health Research Authority and the Medicines and Healthcare products Regulatory Agency for Clinical Trial Authorisation. It is intended that the results of the trial will be presented at international conferences and will be submitted for publication in a peer-reviewed scientific journal. NCT03185000.

DOP016 Efficacy and Safety of Risankizumab in Patients With Moderate to Severe Crohn's Disease With 3 Years of Treatment: Results From the FORTIFY Open-Label Long-Term Extension

DOP016 Efficacy and Safety of Risankizumab in Patients With Moderate to Severe Crohn's Disease With 3 Years of Treatment: Results From the FORTIFY Open-Label Long-Term Extension

P0791 Development and validation of a nomogram for predicting the short-term effectiveness of Ustekinumab in patients with moderate to severe Crohn's disease

P0791 Development and validation of a nomogram for predicting the short-term effectiveness of Ustekinumab in patients with moderate to severe Crohn's disease

Vedolizumab Clearance as a Surrogate Marker for Remission in Inflammatory Bowel Disease Patients: Insights from Real-World Pharmacokinetics.

Background/Objectives: Vedolizumab (VDZ) is approved in the treatment of patients with moderate to severe ulcerative colitis (UC) or Crohn's disease (CD). VDZ exhibits considerable variability in its pharmacokinetic (PK) profile, and its exposure-response relationship is not yet fully understood. The aim was to investigate the variability in VDZ trough levels and PK parameters, to assess the relationship between VDZ PK and biochemical response, as well as clinical and endoscopic outcomes. Methods: We included 61 UC and 45 CD patients. Patients' data and trough VDZ concentrations were retrospectively obtained. Population PK analysis was performed using non-linear mixed-effects modelling with NONMEM (version 7.5). Graphs and statistical analyses were performed using R (version 4.1.3). Results: In total, 116 trough VDZ concentrations from 106 patients were described by a two-compartment model. For a typical patient, clearance (CL) was estimated at 0.159 L/day, while in patients previously treated with anti-TNFα agents, VDZ CL increased by 26.4% on average. In univariate binary logistic regression, VDZ trough concentration was not statistically significant predictor of remission, whereas CL was. Moreover, combined CL and faecal calprotectin (FCP) were a statistically significant predictors of remission. The hazard ratio (HR) for CL above 0.1886 L/day was 0.35 (p = 0.05) and for FCP below 250 µg/g was 2.66 (p = 0.02) in a time-to-event analysis. Conclusions: Our population PK model incorporates the effect of prior anti-TNFα agents on CL, suggesting its association with more severe forms of IBD. VDZ CL emerged as a more robust and clinically relevant predictor of remission in IBD patients than trough concentration.

Analysis of the effectiveness and safety of maintenance treatment with intravenous ustekinumab in inflammatory bowel disease.

Ustekinumab is a monoclonal antibody approved for the treatment of moderate to severe Crohn's disease (CD) and ulcerative colitis (UC). In spite of being an effective treatment, patients may have suboptimal response, or lose it over time. In these cases, ustekinumab intravenous (IV) maintenance therapy has been explored as a rescue option. Retrospective, monocentric, descriptive, observational study that included adult patients with inflammatory bowel disease who received maintenance therapy with intravenous ustekinumab after loss of response to intensified subcutaneous therapy. The primary outcome was a combination of clinical remission with biochemical and/or endoscopic response at week 12 after intravenous intensification. 22 patients were included. The primary outcome was achieved in 36.36% of patients. At week 12, clinical remission was achieved in 40.91% of patients, and biochemical remission in 63.64%. The median HBI score in patients with CD decreased from 6 to 3 points at week 12 (p<0.001), and to 2 points at week 52 (p=0.004). After a median follow-up period of 31.46 months, 81.82% of patients continued their treatment with ustekinumab. No adverse events were reported. Maintenance therapy with intravenous ustekinumab seems to be effective and safe for the rescue of patients with CD and UC who lost response to intensified subcutaneous ustekinumab.

Electrochemical immunosensing of Crohn's disease biomarkers using diazonium salt-grafted crystalline nanocellulose/carbon nanotube-modified electrodes.

Thefirst dual immunosensoris reportedfor the determination of IL-12 and IL-23, two relevant biomarkers of Crohn's disease (CD). The strategy relies on the selective capture of the targets by the respective antibodies which were covalently immobilized onto SPCEs modified with crystalline nanocellulose (CNC) and multi-walled carbon nanotubes (MWCNTs) followed by conjugation with a detector antibody labelled with poly-HRP-Strept and amperometric transduction using the H2O2/HQ system. The combination of CNC, a nanomaterial scarcely exploited in immunosensing, with MWCNTs enables the preparation of a novel dual immunosensor for the determination of CD biomarkers in clinical samples, including faeces. The developed bioplatform exhibits a high reproducibility and selectivity allowing the simultaneous determination of IL-12 and IL-23 using a smaller sample volume and in a much shorter assay time than those reported for each target with commercial ELISA kits. The dual immunosensor was successfully applied to the analysis of raw serum and faeces spiked with IL-12 and IL-23 at the expected levels in patients with severe CD.

Assessment, diagnosis and management of inflammatory bowel disease emergencies

Acute severe ulcerative colitis (ASUC) and Crohn's disease (CD) can present as medical emergencies that require immediate and coordinated care due to the risk of significant morbidity and mortality. This clinical review explores the assessment and management of inflammatory bowel disease emergencies, including ASUC, toxic megacolon, massive haemorrhage, intra-abdominal abscesses, and bowel obstruction. The review highlights the critical importance of prompt diagnosis, patient-centred care, and the integration of multidisciplinary teams (MDTs) in managing these complex cases. It also outlines the clinical approaches, necessary investigations, and both medical and surgical management strategies essential for optimising patient outcomes. The review emphasises the need for healthcare professionals to be equipped with the knowledge and confidence to manage these emergencies effectively, thus enhancing patient care and safety. This article does not aim to explore UC and CD in their entirety but rather aims to focus on the acute emergencies associated with these conditions.

Optimization of dual-energy CT enterography parameters for the assessment of Crohn's disease activity: a retrospective study.

Discuss the selection of imaging parameters in dual-energy CT enterography (DECTE) assessment for patients with Crohn's disease (CD) at different activity levels. This study analyzed data from 55 CD patients who had DECTE and endoscopy from 2020 to 2022. Patients were divided into moderate-severe (Crohn's Disease Endoscopic Index of Severity (CDEIS) ≥ 10) and remission-mild (CDEIS < 10) groups. Imaging indicators such as intestinal wall thickness, iodine concentration (IC), and lesion wall enhancement (ΔHu) were compared, and their correlations with CDEIS scores were analyzed. The receiver operating characteristic (ROC) curve was used to evaluate DECTE's effectiveness in assessing CD activity with multiparameter versus single-parameter methods. Decision curve analysis (DCA) and calibration curve analysis (CCA) were applied to assess patient benefits from the multiparameter assessment model. IC, ΔHu, wall thickness, and comb sign varied significantly between groups (P < 0.05). In the moderate-severe group, ΔHu correlated more strongly with CDEIS than in the remission-mild group. Lesion IC also highly correlated with CDEIS in both groups. DECTE, using multiparameter assessment, achieved an AUC of 0.933(95% CI 0.982-0.999, sensitivity was 0.906, specificity was 0.870) for diagnosing moderate to severe CD activity, surpassing single parameters assessment. CCA and DCA showed that multiparameter assessment had good calibration and net clinical benefits. Compared to moderate-severe CD, the assessment of disease activity in patients with mild-moderate CD was more important using DECTE. A multiparameter assessment can enhance the diagnostic efficacy of DECT for patients with CD.

Long-Term Effectiveness and Safety of Ustekinumab in Crohn's Disease: Results from a Large Real-Life Cohort Study.

Background: Ustekinumab (UST) is an interleukin-12/interleukin-23 receptor antagonist approved for the treatment of Crohn's disease (CD). Only limited real-life data on the long-term outcomes of CD patients treated with UST are available. This study assessed UST's long-term effectiveness and safety in a large population-based cohort of moderate to severe CD patients. Methods: This was a multicenter, retrospective, observational cohort study that included both naïve and biologic-experienced patients treated with UST who achieved clinical remission or clinical response after at least one year of treatment. Clinical activity was scored according to the Harvey-Bradshaw Index (HBI). The primary endpoints were the maintenance or achievement of clinical remission after a further 12-month period of treatment, defined as an HBI of ≤5, and safety. Other endpoints included steroid-free remission, mucosal healing (MH), steroid discontinuation, and the need for treatment optimization during the follow-up. Results: Out of 562 CD patients, after an overall 24-month follow-up, clinical remission was present in 450 (80.0%) patients, and at 12 months, clinical remission was observed in 417/437 (95.4%) patients; 33/125 (26.4%) showed clinical response at 12 months (p = 0.000). A total of 38/103 (36.9%) patients achieved MH. Only 2.1% (12/562), 3% (17/562), and 1.1% (6/562) of patients required surgery, optimization, and re-induction, respectively. Adverse events occurred in eight patients (1.42%). According to a multivariate analysis, the only predictor of long-term remission was the presence of remission at the 12-month follow-up (p = 0.000). Conclusions: Long-term treatment with UST presents good efficacy and safety profiles in CD patients, especially for patients who achieve remission after one year.

Prediction of the Short-Term Effectiveness of Ustekinumab in Patients with Moderate to Severe Crohn's Disease.

Ustekinumab (UST) is recommended as the first-line treatment for patients with moderate to severe Crohn's disease (CD). However, the efficacy of certain patients may be suboptimal and necessitate intensive treatment or modification of the treatment regimen. We sought to establish a nomogram model to predict the short-term effectiveness of UST in moderate to severe CD patients. We established a derivation cohort comprising patients diagnosed with CD and treated with UST at the Sixth Affiliated Hospital of Sun Yat-sen University from May 2020 to July 2023. The patient data, including demographic and clinical characteristics as well as treatment details, were systematically collected. The achievement of clinical remission (defined as Crohn's Disease Activity Index, CDAI < 150, without corticosteroid usage) after induction therapy was the endpoint observed during follow-up. Potential predictors were identified through the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. Subsequently, a multivariate logistic regression analysis was conducted to construct a nomogram model. The predictive accuracy and discriminative power of the model were assessed by Receiver Operating Characteristics (ROC) curves and calibration curves. Decision curve analysis (DCA) was employed to assess the clinical application value of the model. 162 patients were included in the derivation cohort. The predictor's selection was according to the minimum criteria. Prognostic factors, including duration, body mass index (BMI), smoking, extraintestinal manifestations (EIMs), perianal lesions (P), history of Vedolizumab therapy, and albumin levels (ALB), were identified and included in the nomogram. The model showed good discrimination and calibration on internal validation based on the bootstrap method (C-index: 0.843, 95% confidence interval: 0.768-0.903). Moreover, DCA demonstrated that the nomogram was clinically beneficial. We constructed a practical tool to assist clinicians in identifying moderate to severe CD patients who are expected to have a good clinical response to UST, promoting personalized treatment and the development of precision medicine.

Treatment of Vedolizumab With Exclusive Enteral Nutrition in Adult Patients With Moderate to Severe Crohn's Disease (Crohn Exclusive Enteral Nutrition Study).

Despite increasing studies confirming the efficacy of vedolizumab (VDZ) in Crohn's disease (CD), improving the responses to this biologic agent remains challenging in clinical practice. In this article, we investigated the efficacy of combined treatment of VDZ and 16-week exclusive enteral nutrition (EEN) in moderately to severely active CD. From October 2020 to October 2023, 81 patients with moderately to severely active CD treated with VDZ from 2 inflammatory bowel disease centers were retrospectively selected. Forty-one patients received treatment of VDZ with concomitant 16-week EEN (VDZ + EEN cohort), and 40 patients received VDZ treatment alone (VDZ cohort). Clinical and biological outcomes were evaluated. Endoscopic response and mucosal healing were assessed by colonoscopy at weeks 16 and 52. There was no statistically significant difference between 2 groups at baseline for demographic and clinical characteristics. Compared with patients treated with VDZ alone, patients in the VDZ + EEN cohort achieved higher rates of clinical response (84.2% vs 40.0%), clinical remission (81.6% vs 30.0%), endoscopic response (91.4% vs 34.6%), including mucosal healing (85.7% vs 26.9%) at week 16. The superiority of VDZ + EEN treatment sustained in maintenance, with 76.7% (vs 33.3%) clinical response, 70.0% (vs 26.7%) clinical remission, 76.9% (vs 33.3%) endoscopic response, and 61.5% (vs 26.7%) mucosal healing at week 52. None of the patients experienced severe adverse events. VDZ with concomitant 16-week EEN might be an effective and optimized approach with solid efficacy in the induction and maintenance treatment of active CD.

Optimal timeframe for achieving biochemical remission in Crohn's disease patients treated with first-line biologics: A retrospective multicenter study.

Predicting treatment response in Crohn's disease (CD) patients initiating biological therapy is crucial. The first step involves considering symptom control and normalization of C-reactive protein (CRP). However, data on the actual rates of achieving CRP normalization and the appropriate timeframe are lacking. Therefore, we aim to investigate the rate of attaining CRP normalization and identify its optimal timeframe in CD patients initiating biological therapy. In this retrospective multi-center study, we analyzed moderate to severe CD patients initiating biological therapy from January 2012 to July 2023. The primary outcome was the rate and timeframe for achieving CRP normalization. Secondary outcomes included clinical outcomes in patients who achieved CRP normalization and factors associated with early CRP normalization. Of 183 patients, 123 (67.2%) achieved CRP normalization, with a median duration of 3.8 months (interquartile range 1.4 to 7.4 months). The duration and value difference for CRP normalization between anti-tumor necrosis factor agents, ustekinumab, and vedolizumab were statistically insignificant. Cumulative rates of CD-related hospitalization, intestinal resection, and drug discontinuation over 8 years were 11.4%, 2.4%, and 12.2%, respectively. The duration of CRP normalization correlates with drug discontinuation (area under the curve: 0.64). Treatment with 5-aminosalicylic acid (HR 2.77; 95% confidence interval [CI] 1.26-6.11) and high albumin level (HR 1.64, 95% CI 1.04-2.61) favored early CRP normalization, whereas structuring behavior less likely than inflammatory behavior (HR 0.43, 95% CI 0.19-0.96). We have provided the actual rate of achieving CRP normalization and its appropriate timeframe as an initial target in CD treatment.

Safety and Efficacy of Upadacitinib in Crohn's Disease: An Updated Systematic Review.

Crohn's disease (CD) is a chronic inflammatory bowel disease that significantly impacts patient quality of life. This systematic review evaluates the safety and efficacy of upadacitinib, a selective Janus kinase (JAK) inhibitor, in the treatment of CD. A comprehensive literature search was conducted across multiple databases, yielding seven studies published between 2020 and 2024, encompassing 1,481 patients. The review includes randomized controlled trials, post hoc analyses of phase 3 trials, and observational studies. Findings consistently demonstrate upadacitinib's superiority over placebo in inducing and maintaining clinical remission, achieving endoscopic response, and normalizing inflammatory markers. Notably, upadacitinib showed rapid symptom relief, with clinical remission observed as early as five to six days after treatment initiation. Efficacy was observed across various patient populations, including those with prior biologic failure. Long-term studies indicated sustained clinical and endoscopic improvements, with remission rates maintained for up to 30 months. Upadacitinib also demonstrated effectiveness in real-world, treatment-refractory cohorts. Safety profiles were generally consistent with those of other JAK inhibitors. Common adverse events included infections, particularly herpes zoster, and laboratory abnormalities such as neutropenia and elevated creatine kinase. Serious adverse events were infrequent, although careful monitoring is warranted. This review suggests that upadacitinib is a promising treatment option for moderate to severe CD, offering rapid and sustained efficacy with an acceptable safety profile.

Fatal Moans and Bones in Crohn's: A Case of Heterotopic Mesenteric Ossification.

Heterotopic mesenteric ossification (HMO) represents a rare reactive condition characterized by abnormal bone formation within the mesentery. HMO's etiology remains enigmatic, with proposed triggers including trauma-induced metaplasia or bone fragment dislodgment from other sites during abdominal surgery. With fewer than 100 documented cases in the literature, much about this condition remains unknown. In this report, we present a notable case of HMO in a 43-year-old man with a history of severe Crohn's disease and multiple abdominal surgeries. Following a period of unresponsiveness at home, he was admitted to the intensive care unit, where he received palliative care due to a poor prognosis. An autopsy revealed mature, benign bone fragments within the mesentery, alongside severe dehydration, likely exacerbated by decreased oral intake and medication cessation related to his ostomy. Although antemortem imaging revealed HMO, it was misattributed to contrast versus calcification. This case underscores the importance of clinician awareness regarding HMO, particularly its potential implications in inflammatory bowel disease. Early recognition and interdisciplinary collaboration among radiologists, pathologists, and clinicians are paramount in optimizing patient outcomes. Further research is warranted to elucidate this intriguing pathology's pathogenesis and best management strategies.

Case Report on Ustekinumab-Induced Varicella Zoster Infection

Ustekinumab is a human monoclonal antibody typically used to treat moderate to severe plaque psoriasis, psoriatic arthritis, moderate to severe Crohn's disease, or moderate to severe ulcerative colitis (inflammatory bowel disease). Ustekinumab mediates the body's T-cell response by acting as an antagonist against interleukin-12 (IL12) and interleukin-23 (IL23). Although rare, the emergence of severe infections or exacerbation/reactivation of existing infections (bacterial, mycobacterial, fungal, viral) is possible for Ustekinumab. We report a case of a 29-year-old female patient who was prescribed Ustekinumab for Crohn’s disease management. After the commencement of the drug for two doses she developed Varicella pneumonia with ARDS which was subsequently managed.

Targeted surgery combined with postoperative medical therapy for residual disease for severe and multifocal Crohn disease

BackgroundIn patients with multifocal intestinal Crohn disease requiring surgery for complication or uncontrolled disease, resection of all the lesions may lead to diarrhea and malnutrition. MethodsThis is a single-center retrospective review of all patients undergoing targeted surgery for multifocal Crohn disease with at least one residual Crohn disease location left behind. The primary endpoint was the rate of insufficient control of residual Crohn disease lesions requiring redo-surgery targeting these lesions. The rate of clinical remission defined by Harvey–Bradshaw index <4 was studied over time. ResultsFrom January 2012 to August 2022, among 320 patients undergoing surgery for intestinal Crohn disease, 30 met all criteria. Before surgery, patients had received a mean of 3 medical treatment lines; 83% (n = 25) had a clinically active Crohn disease (Harvey–Bradshaw index ≥4). Surgery consisted in ileocolonic (n = 14;47%), small bowel (n = 5;17%) or colonic resection (n = 12;40%) and strictureplasty (n = 4;13%). Operative mortality was nil. Overall postoperative and severe morbidity rates were 15 of 30 (50%) and 3 of 30. Residual lesions were in the small bowel (n = 15;50%), the colon (n = 16;53%), and/or the rectum (n = 16;53%). Twenty-five patients (83%) had postoperative medical therapy. Median follow-up was 65. Six patients (20%) required reoperation for insufficient control of residual lesions at index surgery after a mean of 98 ± 8 months. The clinical remission rate increased from 17% before surgery to 59% at 6–12 months and 71% at 24 months. ConclusionIn patients with multifocal Crohn disease, surgery targeted to severe and complicated lesions combined with postoperative medical treatment is a safe and effective strategy.

Novel Pharmaceuticals and Therapeutics for Tumor Necrosis Factor-Alpha-Resistant Crohn's Disease: A Narrative Review.

Inflammatory bowel disease (IBD) is a medical condition that causes persistent, relapsing inflammation of the gastrointestinal tract. It is an umbrella term encompassing two different conditions: ulcerative colitis (UC) and Crohn's disease (CD). The standard treatment for patients with moderate to severe CD is tumor necrosis factor-α(TNF-α) inhibitors; however, a subset of CD patients face challenges in regardto this disease's treatment. Certain populations of patients with CD may exhibit resistance or develop tolerance to TNF-αinhibitor therapy over time. The recurrent gastrointestinal inflammation associated with CD can severely impact the quality of life and lead to complications for those suffering from this condition. The symptomatic flare-ups these subpopulations continue to experience underscores why such a need for alternative therapies is desperately needed. These alternative therapies not only offer potential benefits for those with TNF-αresistance, but CD may also serve as a superior therapy option for those trying to avoid the adverse effects of CD treatments available today. This review aims to explore and investigate the novel drugs and therapies that are being investigated for the treatment of TNF-αresistant CD, such as upadacitinib, risankizumab, vedolizumab, synbiotics, fecal microbiota transplantation (FMT), and stem cell therapy. Upadacitinib is a Janus kinase inhibitor, Risankizumab is a monoclonal antibody targeting interleukin-23, and Vedolizumab is an integrin receptor antagonist. The latest advancements in CD management have shown encouraging results. Some of these novel drugs and therapies not only offer a potential solution for CD patients exhibiting resistance to TNF-αinhibitors but may also provide a superior alternative for individuals prone to opportunistic infections.

Advancements in Targeted Therapies for the Management of Crohn's Disease: A Comprehensive Review.

Crohn's disease (CD) is a complex clinical condition characterized by persistent gastrointestinal inflammation that leads to episodes of flare-ups and subsequent healing. The treatment options for this disease are heterogeneous as its impact on different patients is also different. This study aims to evaluate the effectiveness of recently approved drugs that specifically target certain pathways within cells that are involved in CD pathogenesis. These medicines include biologics like anti-TNF agents, interleukin inhibitors, and small molecule inhibitors; they work by altering the modulation of immune responses and reducing inflammation. These drugs seem promising in terms of inducing remission in moderate to severe CD among various patient populations. Conversely, it is possible to examine how well these drugs perform using gene expression and molecular markers. By understanding these results along with other ongoing trials, personalized medicine can be used more frequently by doctors who will adopt a strategy for an individual patient, maximizing benefits while minimizing adverse effects.There are still some issues that need to be worked out like the high cost associated with these drugs or immunogenicity risk and infectious complications too. In conclusion, there has been a remarkable improvement in CD management over the past decade with customized drugs leading toward a precision medical era. Further understanding of molecular mechanisms implicated in CD pathogenesis and new therapeutic approaches could potentially improve treatment outcomes among affected individuals.This research is crucial in understanding how CD therapeutics are changing, thus facilitating selection by doctors on the most appropriate methods for individualized patient care.

Therapeutic sequencing in inflammatory bowel disease: Determining the optimal position of vedolizumab for long-term Crohn's disease control using real-world evidence.

Several biologics are available for the treatment of moderate to severe Crohn's disease, but data to optimize their use are scarce. Vedolizumab (VDZ) is a gut-selective anti-lymphocyte trafficking monoclonal antibody that was approved in 2014 for the treatment of moderate to severe Crohn's disease. Based on real-world evidence, a model was developed to examine the effect of VDZ's position in the treatment sequence on clinical outcomes. The aim of this study was to develop a model using real-world data to investigate how the positioning of VDZ in a sequence of biologic therapies for CD affects clinical effectiveness outcomes of quality-adjusted life-years (QALYS), patient-reported disease activity, and surgery rates. A semi-Markov sequential model was developed to identify the optimal position of VDZ in a treatment sequence that included corticosteroids (CS), two biologics, and best supportive care (BSC). Using real-world data, three sequences were compared: VDZ as first (position), second, and last biologic (with anti-tumor necrosis factor alpha agents adalimumab (ADA) and infliximab (IFX) and the anti-interleukin-12 and -23 agent ustekinumab (UST) as alternative biologic treatments). Published real-world evidence informed model inputs. Vedolizumab sequences were compared and ranked based on QALYS, patient-reported outcomes from Crohn's disease activity index scores, or proportion of patients undergoing surgery by the 10-year time horizon for model simulation. Sensitivity analyses were used to evaluate the impact of model input uncertainty. Vedolizumab as the first biologic was the optimal position for this treatment according to all criteria, including yielding the highest QALYs (5.09) versus VDZ in second (4.97) and third (4.96) biologic sequence positions in sequences containing CS, anti-TNFα (aggregated data), UST, and BSC; 1780/2000 (89%) probabilistic simulations. In sequences containing ADA, VDZ, and UST biologics, ADA and VDZ in the first-line biologic position yielded QALYs of 5.09 versus 5.07, respectively. Adalimumab as the first biologic was best for clinical remission. This simulation model using real-world evidence indicates that positioning VDZ or ADA as the first biologic is likely to lead to improved long-term patient outcomes when compared to administering these treatments later or starting with IFX monotherapy.

STEP-CD study: ustekinumab use in paediatric Crohn's disease-a multicentre retrospective study from paediatric IBD Porto group of ESPGHAN.

Ustekinumab is an effective therapy for adult Crohn's disease (CD), but data in paediatric CD patients are scarce. The aim of the study was to describe the real-life effectiveness and safety of ustekinumab in paediatric CD. This is a multicentre review of children with Crohn's disease treated with ustekinumab. The aim of our study was to describe the effectiveness and safety of ustekinumab in paediatric real-life practice. This is a study of the Paediatric IBD (inflammatory bowel disease) Porto group of ESPGHAN. Corticosteroid (CS)- and exclusive enteral nutrition (EEN)-free remission, defined as weighted Paediatric Crohn's Disease Activity Index (wPCDAI) < 12.5, and physician global assessment (PGA) were determined at weeks 12 and 52. A total of 101 children were included at a median age of 15.4 years (IQR 12.7-17.2) with a median follow-up of 7.4 months (IQR 5.6-11.8). Ninety-nine percent had received prior anti-TNF, 63% ≥ 2 anti-TNFα therapies and 22% vedolizumab. Baseline median wPCDAI was 39 (IQR 25-57.5) (71 (70%) patients with moderate-severe activity). Weeks 12 and 52 CS- and EEN-free remission were both 40.5%. Clinical response at week 6, iv induction route and older age at onset of ustekinumab treatment were predictive factors associated with clinical remission at week 12. Seven minor adverse events probably related to ustekinumab were reported. One patient died from an unrelated cause. Conclusion: Our results suggest that ustekinumab is effective and safe in children with chronically active or refractory CD. What is Known: • Ustekinumab is an effective therapy for adult moderate to severe Crohn's disease (CD). • Off-label use of ustekinumab in children is increasing especially in anti-TNF refractory CD. What is New: • Is the largest cohort of real-world use of ustekinumab in paediatric CD to date. • Clinical response at week 6, iv induction and older age at onset of ustekinumab were predictive factors associated with clinical response at week 12.