Proportion of inflammatory bowel diseases patients with suboptimal disease control in daily clinical practice-Real-world evidence from the inflammatory bowel diseases-podcast study.

BACKGROUND: Crohn's disease and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) characterized by a progressive nature of the disease resulting in subsequent intestinal damage, limited efficacy of current treatments and suboptimal disease management and a significant burden for patients. OBJECTIVES: The IBD-PODCAST study aims to estimate the proportion of Crohn's disease and UC patients with suboptimal disease control (SDC) in a real-world setting. METHODS: A non-interventional and cross-sectional study was conducted across 103 sites in 10 countries (Austria, Belgium, Canada, Germany, Greece, Italy, Portugal, Spain, Turkey, and UK). Criteria for SDC were based on STRIDE-II criteria and adapted by an expert panel. RESULTS: 2185 patients (Crohn's disease: n = 1,108, UC: n = 1077) with a mean (SD) age of 44.0 (14.8) years and mean (SD) disease duration of 12.4 (9.2) years were included (52.2% male). Ileal involvement was present in 39.1% of Crohn's disease patients, 35.3% of UC patients had extensive colitis. 77.3% of Crohn's disease and 65.3% of UC patients were on targeted immunomodulators and, according to STRIDE-II-based treatment phases, 85.6% of Crohn's disease and 85.4% of UC patients were assigned to the long-term treatment phase. SDC was detected in 52.2% of Crohn's disease and 44.3% of UC patients predominantly due to impaired quality of life (QoL), clinically significant extraintestinal manifestations, steroid overuse, signs of active inflammation in UC and Crohn's disease, and active fistulas in Crohn's disease. More than one criterion was seen in 37% of patients with SDC. Opportunities for on-label treatment optimization were observed in 49% of Crohn's disease and 61% of UC patients on advanced therapy. CONCLUSION: The high percentage of SDC in this global, real-world cohort suggests a large disease burden and high unmet medical need in IBD patients. Future analysis should focus on monitoring and responding to SDC in this cohort and on patients' QoL.

Upadacitinib in Crohn's disease.

INTRODUCTION: The small molecule and oral selective and reversible Janus kinase (JAK) inhibitor upadacitinib has been approved for the treatment of moderate to severe active Crohn's disease (CD) in adult patients since April 2023 by EMA/FDA. AREAS COVERED: The approval is based on the two induction studies a maintenance study showing that upadacitinib induction and maintenance therapy was superior to placebo. The approval of upadacitinib in CD expands the therapeutic armamentarium for the management of inflammatory bowel diseases (IBD). Upadacitinib is the first and only JAK inhibitor approved in patients with CD and provides a novel mechanism of action and the first advanced oral treatment option for patients with CD. Upadacitinib is approved for the treatment of other immunologically mediated disorders, including ulcerative colitis, rheumatoid arthritis, psoriasis arthritis, axial spondylarthritis, ankylosing spondylitis, and atopic dermatitis. Treatment of atopic dermatitis has been approved from the age of 12 years. EXPERT OPINION: Upadacitinib may cause relevant changes of our current treatment algorithms for Crohn's disease. Further real-world studies and head-to-head comparisons are needed to position upadacitinib in our current treatment algorithms for CD.

Primary Tumor Resection Before Systemic Therapy in Patients With Colon Cancer and Unresectable Metastases: Combined Results of the SYNCHRONOUS and CCRe-IV Trials.

PURPOSE: Chemotherapy is established as primary treatment in patients with stage IV colorectal cancer and unresectable metastases. Data from nonrandomized clinical trials have fueled persistent uncertainty if primary tumor resection (PTR) before chemotherapy prolongs survival. We investigated the prognostic value of PTR in patients with newly diagnosed stage IV colon cancer who were not amenable to curative treatment. PATIENTS AND METHODS: Patients enrolled in the multicenter, randomized SYNCHRONOUS and CCRe-IV trials were included in the analysis. Patients with colon cancer with synchronous unresectable metastases were randomly assigned at 100 sites in Austria, Germany, and Spain to undergo PTR or up-front chemotherapy (No PTR group). The chemotherapy regimen was left at discretion of the local team. Patients with tumor-related symptoms, inability to tolerate surgery and/or systemic chemotherapy, and history of another cancer were excluded. The primary end point was overall survival (OS), and the analyses were performed with intention-to-treat. RESULTS: A total of 393 patients were randomly assigned to undergo PTR (n = 187) or no PTR (n = 206) between November 2011 and March 2017. Chemotherapy was not administered to 6.4% in the No PTR group and 24.1% in the PTR group. The median follow-up time was 36.7 months (95% CI, 36.6 to 37.3). The median OS was 16.7 months (95% CI, 13.2 to 19.2) in the PTR group and 18.6 months (95% CI, 16.2 to 22.3) in the No PTR group (P = .191). Comparable OS between the study groups was further confirmed on multivariate analysis (hazard ratio, 0.944 [95% CI, 0.738 to 1.209], P = .65) and across all subgroups. Patients with serious adverse events were more common in the No PTR group (10.2% v 18.0%; P = .027). CONCLUSION: Among patients with colon cancer and synchronous unresectable metastases, PTR before systemic chemotherapy was not associated with prolonged OS.

Efficacy and Safety of Approximately 3 Years of Continuous Ozanimod in Moderately to Severely Active Ulcerative Colitis: Interim Analysis of the True North Open-label Extension.

BACKGROUNDS AND AIMS: This interim analysis from the True North open-label extension [OLE] study examines efficacy and safety of approximately 3 years of continuous ozanimod treatment in patients with moderately to severely active ulcerative colitis. METHODS: Clinical responders after 52 weeks of ozanimod during the phase 3 True North study, who continued treatment in the OLE, were evaluated. Efficacy, including endoscopic and histological endpoints, was assessed during the OLE for approximately 2 additional years through OLE Week 94, using observed case [OC] and nonresponder imputation [NRI] analyses. Adverse events were monitored from True North baseline through OLE data cutoff and expressed as exposure-adjusted incidence rates. RESULTS: This analysis included 131 patients; 54% had achieved corticosteroid-free remission at True North Week 52. In OC analyses, clinical response, clinical remission, and corticosteroid-free remission were achieved by 91.4%, 69.1%, and 67.9% of patients, respectively, at OLE Week 94 [146 weeks of total treatment]. Similarly, endoscopic improvement, histological remission, and mucosal healing were achieved by 73.3%, 67.3%, and 56.3% of patients, respectively, at OLE Week 94. Efficacy rates were lower using NRI analyses, but maintenance of efficacy was demonstrated through OLE Week 94. No new safety signals emerged from this analysis. Serious infections, malignancy, cardiovascular events, and hepatic events occurred infrequently. CONCLUSIONS: Among patients who achieved clinical response after 1 year of ozanimod treatment during True North, a high percentage sustained clinical and mucosal efficacy over 2 additional years in the OLE. No new safety signals were observed with long-term ozanimod use.

Defining Comprehensive Disease Control for Use as a Treatment Target for Ulcerative Colitis in Clinical Practice: International Delphi Consensus Recommendations.

BACKGROUND AND AIMS: Treatment of ulcerative colitis [UC] requires a patient-centric definition of comprehensive disease control that considers improvements in aspects not typically captured by classical landmark trial endpoints. In an international initiative, we reviewed aspects of UC that affect patients and/or indicate mucosal inflammation, to achieve consensus on which aspects to combine in a definition of comprehensive disease control, using a modified Delphi process. METHODS: The Delphi panel comprised 12 gastroenterologists and one patient advocate. Two gastroenterologists were elected as chairs and did not vote. To inform statements, we asked 18 patients and the panel members about their experiences of remission and reviewed published literature. Panel members voted on statements anonymously in three rounds, with a live discussion before Round 3. Consensus was met if ≥67% of the panel agreed. Statements without consensus in Rounds 1 and 2 were revised or discarded after Round 3. RESULTS: The panel agreed to measure individual patient benefit using a definition of comprehensive disease control that combines aspects currently measured in trials [rectal bleeding, stool frequency, disease-related quality of life, endoscopy, histological inflammatory activity, inflammatory biomarkers, and corticosteroid use] with additional patient-reported symptoms [bowel urgency, abdominal pain, extraintestinal manifestations, fatigue, and sleep disturbance]. The panel agreed on scoring systems and thresholds for many aspects. CONCLUSIONS: Using a robust methodology, we defined comprehensive disease control in UC. Next, we will combine the measurement and scoring of these aspects into a multicomponent tool and will adopt comprehensive disease control as a treatment target in clinical practice and trials.

Clinical trial: Clinical and endoscopic outcomes with ustekinumab in patients with Crohn's disease: Results from the long-term extension period of STARDUST.

BACKGROUND: STARDUST, a phase 3b randomised trial, compared ustekinumab therapeutic strategies in patients with Crohn's disease (CD) using early endoscopic assessment and treat-to-target (T2T) versus standard of care (SoC). AIM: To assess the efficacy of ustekinumab extended treatment in a long-term extension (LTE) of up to 104 weeks with dosing adapted according to clinical, biomarker and endoscopy outcomes. METHODS: Adults with moderately-to-severely active CD received intravenous ustekinumab approximating 6 mg/kg at Week 0 and subcutaneous ustekinumab 90 mg at Week 8. At Week 16, 440 ≥70-point responders were randomised to T2T or SoC and 323 entered the LTE. At Week 48, a unified, protocol-defined ustekinumab dose frequency escalation/de-escalation was applied based on achieving endoscopic remission and corticosteroid-free clinical remission. Achieving corticosteroid-free clinical remission and biomarker remission at consecutive visits determined ustekinumab dosing frequency. Dichotomous variables were analysed using non-responder imputation. RESULTS: Among patients who entered the LTE, 7.7%, 48.6% and 43.7% received doses every 4, 8 and 12 weeks, respectively. Ustekinumab dose frequency was escalated in 23.5% and de-escalated in 19.7%. Endoscopic response and remission rates were 28.9% and 10.73% (all randomised) and 39.3% and 14.6% (patients entering the LTE), respectively, at Week 104. Clinical remissiona rates at week 104 were 50.2% (all randomised) and 68.4% (patients entering the LTE). There were no new safety signals. CONCLUSION: STARDUST LTE is the first interventional ustekinumab efficacy study to show a favourable benefit-risk profile with preservation of clinical and endoscopic outcomes through Week 104 using flexible, algorithm-driven dose adjustment including de-escalation.

Outcomes and Endpoints of Postoperative Recurrence in Crohn's Disease: Systematic Review and Consensus Conference.

BACKGROUND: Outcomes after ileocolonic resection in Crohn's disease [CD] are heterogeneous, and a clear definition of postoperative recurrence remains to be determined. Our Endpoints Working Group of the International Organization for the study of Inflammatory Bowel Disease [IOIBD] aimed to standardise postoperative outcomes, to discuss which endpoints should be used for postoperative clinical trials, and to define those which could be used in trials or registries. METHODS: Based on a systematic review of the literature, recommendations and statements were drafted and sent to all IOIBD members for a first round of voting. Recommendations and statements were revised based on the voters' comments during a consensus hybrid conference open to all IOIBD members. If no agreement was reached after two rounds of voting, the statement was excluded. RESULTS: In the systematic review, 3071 manuscripts were screened of which 434 were included. Sixteen recommendations were identified, of which 11 were endorsed. Recommendations and statements include that endoscopy remains the gold standard and should be used as a short-term primary endpoint in both observational cohorts and randomised controlled trials. Clinical symptoms classically used in clinical trials for luminal CD are not reliable in this specific situation. For that reason, longer-term endpoints should be based on the evidence of macroscopic inflammation assessed by imaging techniques, endoscopy, or as reflected by the presence of complications. CONCLUSIONS: Agencies recommend the use of clinical evaluations, as in the case of luminal CD, and do not recognise primary endpoints based solely on endoscopy. This consensus has led to agreement on the need to define postoperative endoscopy-based and/or imaging-based endpoints.

Clinical profiles and outcomes in patients with inflammatory bowel disease receiving standard and escalated doses of targeted therapies: findings from a global real-world study.

OBJECTIVE: Although dosing regimens of targeted therapies (TT) for ulcerative colitis (UC) and Crohn's disease (CD) are guided by market authorizations and clinical guidelines, little is known about clinical guideline adherence or outcomes in patients receiving escalated doses of TT due to lack of response. This real-world study explored the prevalence of dose escalation and compared outcomes between patients receiving standard and escalated TT doses. METHODS: Data were from the 2020-2021 Adelphi Disease Specific Programme for inflammatory bowel disease, a cross-sectional survey of gastroenterologists and their UC and CD patients across five European countries and the US. Physicians provided retrospective data collection of patient demographics, clinical characteristics, treatment history, and satisfaction; patients reported quality-of-life and work productivity. Patients were grouped by TT maintenance dose; standard and escalated dose groups were compared. Outcomes were adjusted for time on current TT and severity at current TT initiation using regression analyses. RESULTS: Of 1,241 UC and 1,477 CD patients, 19.1% and 24.1%, respectively, received escalated TT doses. Despite escalation, a substantial proportion of patients had not achieved remission, had moderate or severe disease activity, or were flaring. Most physicians were not fully satisfied with treatment in the escalated dose group and were more likely to switch patients to another treatment regimen than patients on standard dose. CONCLUSION: Dose escalation is not always an effective approach to resolve inadequate or loss of response in UC and CD, highlighting a need for more therapeutic options or alternative treatment strategies in patients unresponsive to TT.

The PROPER Study: A 48-Week, Pan-European, Real-World Study of Biosimilar SB5 Following Transition from Reference Adalimumab in Patients with Immune-Mediated Inflammatory Disease.

BACKGROUND: The non-interventional PROPER study generated real-world evidence on clinical outcomes following transition in routine practice from reference adalimumab to the EMA-approved SB5 biosimilar adalimumab in patients with immune-mediated inflammatory disease. METHODS: Adults with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), Crohn's disease (CD), or ulcerative colitis (UC) were enrolled at 63 sites across Europe. Eligible patients received ≥ 16 weeks of routine treatment with reference adalimumab before transitioning to SB5, and were followed for 48 weeks post-transition. The primary objective was to evaluate candidate predictors (clinically relevant baseline variables with incidence ≥ 15% by indication cohort) associated with persistence on SB5 at 48 weeks post-initiation. Key primary outcome measures were persistence on SB5 (estimated by Kaplan-Meier methodology) and clinical characteristics and disease activity scores at the time of transition to SB5 treatment (baseline). RESULTS: A total of 955 eligible patients were enrolled (RA, n = 207; axSpA, n = 127; PsA, n = 162; CD, n = 447; UC, n = 12), of whom 932 (97.6%) completed follow-up and 722 (75.6%) were still receiving SB5 at week 48. Kaplan-Meier estimates (95% confidence interval, CI) of persistence on SB5 at week 48 for RA, axSpA, PsA, and CD were 0.86 (0.80-0.90), 0.80 (0.71-0.86), 0.81 (0.74-0.86), and 0.72 (0.67-0.76), respectively. The single candidate predictor associated with probability of SB5 discontinuation before week 48 was female sex [RA, axSpA, and CD cohorts; HR (95% CI): 3.53 (1.07-11.67), 2.38 (1.11-5.14), and 2.21 (1.54-3.18), respectively]. Disease activity scores remained largely unchanged throughout the study, with proportions by cohort in remission at baseline versus week 48 being 59.2% versus 57.2%, 81.0% versus 78.0%, 94.7% versus 93.7%, and 84.0% versus 85.1% for patients with RA, axSpA, PsA, and CD, respectively. Similarly, the SB5 dosing regimen remained unchanged for the majority of patients from baseline to week 48, the most common regimen being 40 mg every 2 weeks. In total, 232 patients (24.3%) reported at least one adverse drug reaction, and most events were mild; eight patients (3.9%) in the RA cohort experienced nine serious adverse events (SAEs; two possibly related to SB5); eight patients (4.9%) in the PsA cohort experienced nine SAEs (one possibly related to SB5); 22 patients (4.9%) in the CD cohort experienced 27 SAEs (four possibly related to SB5); and no SAEs were observed in the UC cohort. CONCLUSIONS: With the exception of female sex in RA, axSpA, and CD, none of the candidate predictors were associated with SB5 discontinuation. Persistence on SB5 was high, treatment effectiveness was maintained, and no safety signals were detected. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov: NCT04089514.

Difficult-to-treat inflammatory bowel disease: results from an international consensus meeting.

Many patients with inflammatory bowel disease (IBD) have persistent symptoms and disease activity despite the best available medical or surgical treatments. These patients are commonly referred to as having difficult-to-treat IBD and need additional therapeutic strategies. However, the absence of standard definitions has impeded clinical research efforts and comparisons of data. Under the guidance of the endpoints cluster of the International Organization for the Study of Inflammatory Bowel Disease, we held a consensus meeting to propose a common operative definition for difficult-to-treat IBD. 16 participants from 12 countries voted on 20 statements covering various elements of difficult-to-treat IBD, such as failure of medical and surgical treatments, disease phenotypes, and specific complaints from patients. "Agreement" was defined as at least 75% consensus. The group agreed that difficult-to-treat IBD is defined by the failure of biologics and advanced small molecules with at least two different mechanisms of action, or postoperative recurrence of Crohn's disease after two surgical resections in adults, or one in children. In addition, chronic antibiotic-refractory pouchitis, complex perianal disease, and comorbid psychosocial complications that impair disease management also qualified as difficult-to-treat IBD. Adoption of these criteria could serve to standardise reporting, guide enrolment in clinical trials, and help identify candidates for enhanced treatment strategies.

Real-world experience with subcutaneous infliximab: broadening treatment strategies for inflammatory bowel disease.

INTRODUCTION: The first subcutaneous (SC) formulation of infliximab (IFX), CT­P13 SC, has been approved in Europe and Australia, including for the treatment of inflammatory bowel disease (IBD). AREAS COVERED: We provide a comprehensive overview of available clinical trial and real-world data for IFX SC treatment of IBD, focusing on the potential benefits of switching from IFX intravenous (IV) to IFX SC. We evaluate emerging evidence for IFX SC treatment for difficult-to-treat IBD, use as monotherapy, and suitability for patients receiving escalated IFX IV doses. Therapeutic drug monitoring approaches and patient and healthcare system perspectives on IFX SC are also discussed. EXPERT OPINION: IFX SC represents a significant treatment innovation in the tumor necrosis factor inhibitor class after approximately 20 years of IFX IV availability. Evidence suggests that IFX SC is well tolerated and is associated with high patient acceptance and satisfaction. In addition, effectiveness is maintained in patients with stable disease following switch from IFX IV. Switching may be advisable, given the clinical benefits of IFX SC and its potential to improve healthcare service capacity. There are several areas requiring further research, including the role of IFX SC in difficult-to-treat and refractory disease, and the feasibility of IFX SC monotherapy.

Ustekinumab improves health-related quality of life in patients with moderate-to-severe Crohn's disease: Results up to Week 104 of the STARDUST trial.

BACKGROUND: STARDUST is a phase 3b randomized controlled trial comparing two ustekinumab treatment strategies in patients with Crohn's disease (CD): treat-to-target (T2T) versus standard of care (SoC). OBJECTIVE: We investigated the effect of a T2T or SoC ustekinumab treatment strategy on health-related quality of life (HRQoL) and work productivity and activity impairment (WPAI) over a 2-year follow-up period. METHODS: At Week 16, adult patients with moderate-to-severe active CD were randomized 1:1 to either T2T or SoC treatment groups. We assessed changes from baseline in HRQoL measures (Inflammatory Bowel Disease Questionnaire [IBDQ], EuroQoL 5-dimension 5-level [visual analogue scale and index], Functional Assessment of Chronic Illness Therapy-Fatigue, Hospital Anxiety and Depression Scale-Anxiety and -Depression) and the WPAI questionnaire in two patient populations: randomized analysis set (RAS, patients randomized to either T2T or SoC at Week 16 and completed Week 48) and modified RAS (mRAS, patients who entered the long-term extension [LTE] period at Week 48). RESULTS: At Week 16, 440 patients were randomized to T2T (n = 219) or SoC (n = 221) arms; 366 patients completed Week 48. Of these, 323 patients entered the LTE and 258 patients completed 104 weeks of treatment. In the RAS population, percentages of patients achieving IBDQ response and remission were not significantly different between treatment arms at Weeks 16 and 48. In the overall mRAS population, IBDQ response and remission increased over time from Weeks 16-104. In both populations, improvements from baseline in all HRQoL measurements were observed at Week 16 and maintained until either Week 48 or Week 104, respectively. In both populations, improvements from baseline in T2T and SoC arms at Weeks 16, 48 or 104 in WPAI domains were observed. CONCLUSION: Independent of treatment strategy (T2T or SoC), ustekinumab was effective in improving HRQoL measurements and WPAI over a period of 2 years.

Malignancy rates in Crohn's disease patients with perianal fistula: A German retrospective cohort study.

BACKGROUND: Patients with inflammatory bowel disease are at increased risk of colorectal and extra-intestinal cancer. However, the overall cancer risk in patients with Crohn's disease (CD) with perianal fistulas (PF) (CPF) and those with CD without PF (non-PF CD) is unclear. OBJECTIVE: To describe the prevalence and incidence of cancer in patients with CPF and non-PF CD, and to estimate incidence rate ratio (IRR) of cancer between CPF and non-PF CD groups. METHODS: A retrospective cohort study was conducted using the German InGef (Institute for Applied Health Research Berlin) research database. Patients with a CD record and PF from 1 January 2013 to 31 December 2014 were identified and followed up from 1 January 2015 until the first occurrence of cancer, end of health insurance contributing data, death, or end of study period (31 December 2020). Prevalence of any type of cancer including patients with CD diagnosed with cancer in the selection period and incidence of cancer excluding patients with CD diagnosed with cancer in the selection period were calculated. RESULTS: In total, 10,208 patients with CD were identified. Of 824 patients with CPF (8.1%), 67 had had a malignancy (6-year period crude malignancy prevalence 8.13% [95% confidence interval (CI) 6.36%-10.21%]), which was lower than patients with non-PF CD (19.8% [95% CI 19%-20.6%]). Incidence (per 100,000 person-years) in patients with CPF was 1184 (95% CI 879-1561) and in non-PF CD was 2365 (95% CI 2219-2519). There was no significant difference in the adjusted IRR of cancer for the CPF group compared with the non-PF CD group (0.83 [95% CI 0.62-1.10]; p = 0.219). CONCLUSION: There was no significant difference in the incidence of any cancer in patients with CPF compared with non-PF CD. However, patients with CPF had a higher numerical risk of cancer than the general German population.

Has the therapeutical ceiling been reached in Crohn's disease randomized controlled trials? A systematic review and meta-analysis.

BACKGROUND AND AIMS: The availability of biological agents for inflammatory bowel disease has increased over the past years. In this systematic review and meta-analysis, we aimed to explore time trends in clinical response and clinical remission rates in Crohn's disease (CD) patients treated with biologics while discussing the need for new strategies. METHODS: MEDLINE, Cochrane, and ISI Web of Science databases were searched for randomized placebo-controlled trials with biological agents in moderate-to-severe CD patients. Sub-group and meta-regression analyses compared treatment and placebo by calculating the pooled odds ratios of clinical remission and clinical response, across time categories and publication year. We also estimated the proportion of patients achieving clinical remission and clinical response by comparing both groups according to the publication year. RESULTS: Twenty-five trials were included in the systematic review, which enrolled 8879 patients between 1997 and 2022. The clinical remission and clinical response odds, in induction and maintenance, have been constant over time, as no statistically significant differences were found between time categories (interaction p-values: clinical remission [induction, p = 0.19; maintenance, p = 0.24]; clinical response [induction, p = 0.43; maintenance, p = 0.59]). In meta-regression analyses, publication year did not influence these outcomes (clinical remission [induction, OR 1.01{95% CI 0.97-1.05}, p = 0.72; clinical response [induction, OR 1.01{95% CI 0.97-1.04]; p = 0.63; maintenance, OR 1.03{95% CI 0.98-1.07}; p = 0.21]), with the exception of clinical remission in maintenance studies, which presented a decreased effect (odds ratio 0.97{95% CI 0.94-1.00}, p = 0.03]). CONCLUSIONS: Our review highlights that the odds of clinical outcomes in CD patients receiving biological treatment relative to placebo have been stable in the last decades.

Impact of Crohn's Disease Therapies on Histology in Randomized Controlled Trials: Systematic Review With Meta-analysis.

BACKGROUND: The effectiveness of Crohn's disease treatments for inducing histological outcomes has not been addressed systematically. We performed a systematic review and meta-analysis of randomized controlled trials in Crohn's disease to assess the impact of therapies on mucosal histopathology. METHODS: Databases (MEDLINE, CENTRAL, Web of Science, EMBASE) were searched for randomized controlled trials including adult patients and evaluating histological outcomes. Risk of bias was evaluated using the Critical Appraisal Skills Programme. Histological outcomes, pooled frequencies, pooled odds ratios, and standard mean differences of the histological scores were compared between the intervention and placebo groups using a random-effects model. RESULTS: Out of 2070 records, 10 studies were included. The quality of the studies ranged from moderate to high, but they were clinically and methodologically diverse. All interventions were superior to placebo. Histological response was achieved by 68% of patients, and 38% achieved remission. Pooled odds ratio for histological remission in patients receiving intervention vs placebo was 4.14 (95% CI, 2.28-7.50; I2 0%; P < .01). Heterogeneity in histological response estimates was significant, and subgroup analysis of the odds ratio results was limited by the low number of studies per group. The standard mean difference of histological scores was higher for patients receiving intervention in both induction and maintenance studies (-2.95; 95% CI, -4.17 to -1.74; I2 83% P < .00; and -2.58; 95% CI, -3.89 to -1.27; I2 56% P < .00). CONCLUSIONS: Crohn's disease therapies are effective for achieving histological outcomes. Adherence to recently published consensus on histopathology harmonization assessment in Crohn's disease would facilitate adequate comparison between studies in the future.

We performed a systematic review and meta-analysis of randomized controlled trials in Crohn's disease with the primary objective of assessing therapeutic histologic outcomes (response and remission). Our results show that CD therapies are effective in achieving these outcomes.

The Modified Mucosal Inflammation Noninvasive Index and Endoscopic Remission in Adults With Crohn's Disease.

The Mucosal Inflammation Noninvasive Index is a validated noninvasive tool to assess endoscopic remission in pediatric Crohn's disease. In this study, we evaluated a modified version of the Mucosal Inflammation Noninvasive Index on adult cohorts to explore its validly in adult Crohn's disease.

CORE-IBD: A Multidisciplinary International Consensus Initiative to Develop a Core Outcome Set for Randomized Controlled Trials in Inflammatory Bowel Disease.

BACKGROUND & AIMS: End points to determine the efficacy and safety of medical therapies for Crohn's disease (CD) and ulcerative colitis (UC) are evolving. Given the heterogeneity in current outcome measures, harmonizing end points in a core outcome set for randomized controlled trials is a priority for drug development in inflammatory bowel disease. METHODS: Candidate outcome domains and outcome measures were generated from systematic literature reviews and patient engagement surveys and interviews. An iterative Delphi process was conducted to establish consensus: panelists anonymously voted on items using a 9-point Likert scale, and feedback was incorporated between rounds to refine statements. Consensus meetings were held to ratify the outcome domains and core outcome measures. Stakeholders were recruited internationally, and included gastroenterologists, colorectal surgeons, methodologists, and clinical trialists. RESULTS: A total of 235 patients and 53 experts participated. Patient-reported outcomes, quality of life, endoscopy, biomarkers, and safety were considered core domains; histopathology was an additional domain for UC. In CD, there was consensus to use the 2-item patient-reported outcome (ie, abdominal pain and stool frequency), Crohn's Disease Activity Index, Simple Endoscopic Score for Crohn's Disease, C-reactive protein, fecal calprotectin, and co-primary end points of symptomatic remission and endoscopic response. In UC, there was consensus to use the 9-point Mayo Clinic Score, fecal urgency, Robarts Histopathology Index or Geboes Score, fecal calprotectin, and a composite primary end point including both symptomatic and endoscopic remission. Safety outcomes should be reported using the Medical Dictionary for Regulatory Activities. CONCLUSIONS: This multidisciplinary collaboration involving patients and clinical experts has produced the first core outcome set that can be applied to randomized controlled trials of CD and UC.

Composite outcomes in observational studies of Crohn's disease: a systematic review and meta-analysis.

Background: This systematic review and meta-analysis aims to assess composite and aggregate outcomes of observational studies in Crohn's disease and to evaluate whether the number and type of variables included affect the frequency of the outcome. Methods: MEDLINE [via PubMed], Scopus and Web of Science were searched to identify observational studies that enrolled patients with Crohn's disease and evaluated a composite or aggregate outcome. The proportion of patients achieving the outcome was determined and a random-effects meta-analysis was performed to evaluate how the frequency of each outcome varies according to the reporting of predefined variables. Results: From 10,257 identified records, 46 were included in the qualitative analysis and 38 in the meta-analysis. The frequency for composite and aggregate outcomes was 0.445 [95% confidence interval (CI): 0.389-0.501] and 0.140 (95% CI: 0.000-0.211), respectively. When comparing composite outcomes by number of included variables, the frequency was 0.271 (95% CI: 0.000-0.405) and 0.698 (95% CI: 0.651-0.746), for one and six variables, respectively. The frequency of the composite outcome varied according to the identity of the variables being reported. Specific pairs of predefined variables had a significant effect in the frequency of composite outcomes. Conclusion: Composite outcomes with increasing number of predefined variables show an increase in frequency. Outcomes including variables such as 'Surgery' and 'Steroids' had higher frequencies when compared with the ones that did not include these variables. These results show that the frequency of composite outcomes is dependent on the number and type of variables being reported.