Abushamma, Suha

Abstract Background: Placebo response is crucial in interpreting treatment efficacy in ulcerative colitis (UC) trials. While it has been broadly studied, it remains underexplored in trials involving the growing number of biologics and small molecules for ulcerative colitis. Methods: We systematically searched PubMed, Embase, Scopus, Web of Science, and Cochrane CENTRAL from inception to November 13, 2024. Eligible studies were induction-phase RCTs, including adult patients with moderate-to-severe UC who received a biologic and a small-molecule against a placebo. Primary outcomes were pooled clinical and endoscopic response and remission rates. Safety outcomes included adverse events (AEs), serious adverse events (SAEs), and withdrawal rates. Random-effect models were used for meta-analysis. Meta-regression identified predictors of placebo outcomes. Results: 26 induction RCTs with 3,937 placebo-treated patients were included. IL inhibitor trials had the highest placebo clinical response (36%) and endoscopic remission (21%), while JAK inhibitors had the lowest (21% and 2%). Overall placebo rates were 34% for clinical response, 8% for clinical remission, 19% for endoscopic response, and 11% for endoscopic remission. Adverse events occurred in 54%, SAEs in 8%, and withdrawals in 18%. Younger age and longer follow-up were linked to higher placebo responses; recent trials showed reduced endoscopic effects. Conclusion: These findings highlight the need to account for placebo variability in trial design and interpretation, particularly as biologic and small-molecule therapies continue to expand in UC treatment.

Abstract Background and Aims Over 10% of patients with Crohn’s disease require permanent ileostomy. We aimed to summarize the existing data on diagnosis, definitions of recurrence, and management of Crohn’s disease patients with permanent ileostomy. Methods MEDLINE, Embase, and CENTRAL databases were searched from inception to February 6, 2024. Randomized controlled trials, cohort and cross-sectional studies, and case series of more than 5 patients reporting on postoperative recurrence or the need for surgery in patients with Crohn’s disease and permanent ileostomy were included. Search results were independently screened, and full text of all titles meeting eligibility criteria was obtained. Outcomes of interest included diagnostic techniques, recurrence definitions, and management approaches. We estimated pooled rates (with 95% confidence interval [CI]) of recurrence. Results Thirty cohort studies including 2055 Crohn’s patients with permanent ileostomy were included (53% female, median age at the time of ileostomy creation 32 years, the most common reason for ileostomy was refractory disease). The postoperative recurrence rate was 27% (95% CI, 21.3–33.3, 26 studies, 451/1805 patients). Modalities for diagnosis of Crohn’s disease recurrence were symptoms (15 studies), endoscopy (4 studies), histology from endoscopic biopsies (2 studies), imaging (5 studies), and surgery (22 studies). The reported definitions of recurrence for each modality were heterogeneous. Conclusions There is a lack of standardized monitoring tools and criteria for diagnosing recurrence in patients with Crohn’s disease and permanent ileostomy. The results of this systematic review will form the basis of a global expert recommendation exercise focused on developing management standards and trial endpoints for this condition.

Abstract Background Inflammatory bowel disease (IBD)–associated peripheral spondyloarthritis (pSpA) decreases quality of life and remains poorly understood. Given the prevalence of this condition and its negative impact, it is surprising that evidence-based disease definitions and diagnostic strategies are lacking. This systematic review summarizes available data to facilitate development and validation of diagnostics, patient-reported outcomes, and imaging indices specific to this condition. Methods A literature search was conducted. Consensus or classification criteria, case series, cross-sectional studies, cohort studies, and randomized controlled trials related to diagnosis were included. Results A total of 44 studies reporting data on approximately 1500 patients with pSpA were eligible for analysis. Data quality across studies was only graded as fair to good. Due to large heterogeneity, meta-analysis was not possible. The majority of studies incorporated patient-reported outcomes and a physical examination. A total of 13 studies proposed or validated screening tools, consensus, classification, or consensus criteria. A total of 28 studies assessed the role of laboratory tests, none of which were considered sufficiently accurate for use in diagnosis. A total of 17 studies assessed the role of imaging, with the available literature insufficient to fully endorse any imaging modality as a robust diagnostic tool. Conclusions This review highlights existing inconsistency and lack of a clear diagnostic approach for IBD-associated pSpA. Given the absence of an evidence-based approach, a combination of existing criteria and physician assessment should be utilized. To address this issue comprehensively, our future efforts will be directed toward pursuit of a multidisciplinary approach aimed at standardizing evaluation and diagnosis of IBD-associated pSpA.

Abstract Background and Aims Perianal fistuliing Crohn’s disease [PFCD] is an aggressive phenotype of Crohn’s disease defined by frequent relapses and disabling symptoms. A novel consensus classification system was recently outlined by the TOpCLASS consortium, which seeks to unify disease severity with patient-centred goals but has not yet been validated. We aimed to apply this to a real-world cohort and to identify factors that predict transition between classes over time. Methods We identified all patients with PFCD and at least one baseline and one follow-up pelvic MRI [pMRI]. TOpCLASS classification, disease characteristics, and imaging indices were collected retrospectively at time periods corresponding with respective MRIs. Results We identified 100 patients with PFCD, of whom 96 were assigned TOpCLASS Classes 1–2c at baseline. Most patients [78.1%] started in Class 2b, but changes in classification were observed in 52.1% of all patients. Male sex [72.0%, 46.6%, 40.0%, p = 0.03] and prior perianal surgery [52.0% vs 44.6% vs 40.0%, p = 0.02] were more frequently observed in those with improved class compared to unchanged and worsened class. Baseline pMRI indices were not associated with changes in classification; however, greater improvements in mVAI, MODIFI-CD, and PEMPAC were seen among those who improved. Linear mixed effect modelling identified only male sex [-0.31, 95% CI -0.60 to -0.02] with improvement in class. Conclusion The TOpCLASS classification highlights the dynamic nature of PFCD over time. However, our ability to predict transitions between classes remains limited and requires prospective assessment. Improvement in MRI index scores over time was associated with a transition to lower TOpCLASS classification.