Ha, Christina

Abstract Background While biologic and small molecule therapies have expanded treatment options for moderate to severe ulcerative colitis (UC), prior research revealed that only 26% of patients in routine practice would have qualified for pivotal randomized controlled trials (RCTs) due to stringent eligibility criteria. This study aimed to evaluate contemporary clinical trial eligibility for UC patients in a tertiary care setting based on more recently approved therapies. Methods We performed a retrospective cohort study of adult patients with moderate to severe UC (total Mayo score ≥6) seen between January 2022 and February 2023. Inclusion and exclusion criteria from seven phase III RCTs conducted between 2012 and 2022 (eg, VARSITY, UNIFI, OCTAVE, LUCENT) were applied to determine patient eligibility and identify reasons for ineligibility. Results Of 150 patients (mean age 44.9 years; 55.7% male), only 42.7% were eligible for at least one RCT. The most common exclusion factor was current or prior medication use, followed by anemia, dysplasia, and disease extent. Trial eligibility did not significantly differ by age, gender, or disease duration. Conclusions Despite modest improvements since 2012, over half of real-world UC patients remain ineligible for current RCTs. Expanding inclusion criteria, especially regarding prior medication exposure, and adopting more inclusive trial designs may enhance external validity. Addressing disparities in trial access and participation remains essential to ensuring equitable representation and improving clinical applicability of RCT findings.

Crohn's disease (CD) is an idiopathic inflammatory disorder of unknown etiology with genetic, immunologic, and environmental influences. The incidence of CD has steadily increased over the past several decades. The diagnosis and treatment of patients with CD has evolved since the last practice guideline was published. These guidelines represent the official practice recommendations of the American College of Gastroenterology and were developed under the auspices of the Practice Parameters Committee for the management of adult patients with CD. These guidelines are established for clinical practice with the intent of suggesting preferable approaches to medical problems as established by interpretation and collation of scientifically valid research, derived from extensive review of published literature. When exercising clinical judgment, health care providers should incorporate this guideline along with patient's needs, desires, and their values to care for patients fully and appropriately with CD. Shared decision-making with the patient is advocated. This guideline is intended to be flexible, not necessarily indicating the only acceptable approach, and should be distinguished from standards of care that are inflexible and rarely violated. To evaluate the level of evidence and strength of recommendations, we used the Grading of Recommendations Assessment, Development, and Evaluation system. The Committee reviews guidelines in depth, with participation from experienced clinicians and others in related fields. The final recommendations are based on the data available at the time of the production of the document and may be updated with pertinent scientific developments later.

Abstract Background Tumor necrosis factor-like ligand 1A (TL1A) is upregulated in inflammatory bowel disease and believed to promote inflammation and intestinal fibrosis. RO7790121, an anti-TL1A antibody, showed promising results in the phase IIa TUSCANY trial.1 Here we report post-hoc analyses of patient-reported outcomes from the TUSCANY-2 trial. Methods This phase IIb, multicenter, randomized, double-blind, treat-through, dose-ranging study evaluated RO7790121 in patients (pts) aged 18–75 years with moderately to severely active ulcerative colitis (UC) (total Mayo score [MS] ≥6, endoscopic subscore ≥2). Pts were randomized to receive subcutaneous (SC) RO7790121 50mg, 150mg, 450mg or matched placebo (PBO) monthly during the 12-week induction period, and SC RO7790121 50mg, 150mg or 450mg monthly during the 40-week treat-through maintenance period. To assess efficacy of RO7790121 in supporting pts achieving early symptomatic improvement, rectal bleeding (RB), stool frequency (SF) and partial modified MS (RB+SF) were evaluated at baseline and Weeks 2, 4, 8, 12 and 14. The exploratory endpoint of symptomatic remission, defined as a RB subscore of 0 and a SF subscore of 0 or 1, was assessed throughout induction. Safety was assessed throughout the study. Results Overall, 245 pts received ≥1 dose of RO7790121 or PBO. At Week 2, pts receiving RO7790121 were more likely to report a RB subscore of 0 (34% RO7790121; 20% PBO) and less likely to report a RB subscore of 2 or 3 (25% RO7790121; 40% PBO) (Figure). Improvements in SF increased from Week 2 and throughout induction, with ~60% of pts receiving RO7790121 reporting a SF subscore of 0 or 1 at Weeks 12 and 14, vs ~40% for PBO. Greater rates of symptomatic remission were observed in pts receiving RO7790121 vs PBO throughout induction and from Week 2 (17.5% RO7790121; 8.9% PBO) (Table). Treatment-emergent adverse events (TEAEs) were reported during induction in 117/245 pts, the most common (reported in ≥5% of pts in any treatment group) were nausea, urinary tract infection and UC (highest in the 50mg arm), anemia (highest in the placebo arm) and fatigue, headache and pyrexia (highest in the 450mg arm). Serious TEAEs were reported in ten pts during induction (PBO=4; 50mg=3; 450mg=3); two were treatment related (PBO=1; 450mg=1). There were six treatment discontinuations due to TEAEs and a generally similar safety profile was observed during the maintenance period. Conclusion Greater and earlier improvements in RB and SF were observed in pts receiving RO7790121 vs PBO. These results indicate early symptom relief and a favorable safety profile for pts treated with RO7790121, supporting its further clinical development. RO7790121 is currently being evaluated in phase III studies (NCT06589986 and NCT06588855). References 1.Danese S, Klopocka M, Scherl EJ, et al. Anti-TL1A antibody PF-06480605 safety and efficacy for ulcerative colitis: A phase 2a single-arm study. Clin GastroenterolHepatol. 2021;19(11):2324-2332.e6. http://doi.org/10.1016/j.cgh.2021.06.011

Abstract Background Etrasimod is an oral, once daily (QD), selective sphingosine 1-phosphate1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). We assessed the benefit of etrasimod monotherapy and the impact of concomitant corticosteroids (CS) and/or 5-aminosalicylates (5-ASA) therapy. Methods In ELEVATE UC 52 and ELEVATE UC 12, patients with moderately to severely active UC were randomized 2:1 to etrasimod 2 mg QD or placebo for 52 and 12 weeks, respectively. Oral CS or 5-ASA were allowed at baseline. Patients in the monotherapy subgroup received etrasimod or placebo without concomitant CS and/or 5-ASA at baseline. Predefined primary (clinical remission) and key secondary efficacy endpoints aligned with those from both trials and were assessed at Week 12 and Week 52. Safety was assessed up to Week 52. Results Clinical remission rates at Weeks 12 and 52 were significantly higher for etrasimod compared with placebo in patients receiving monotherapy (Week 12: 26.2% vs 4.8%; Week 52: 35.7% vs 4.0%). Differences vs placebo were statistically significant for all predefined endpoints at both time points in patients receiving monotherapy or etrasimod with concomitant 5-ASA only (all P < .05); numerical differences, due to small sample sizes, vs placebo were observed for all endpoints in the CS only and CS + 5-ASA subgroups. Safety was consistent with the overall population. Conclusions Etrasimod monotherapy showed consistent efficacy and safety vs placebo; no apparent benefit was observed with concomitant CS and/or 5-ASA in patients receiving etrasimod. Clinical trial registration NCT03945188; NCT03996369.

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.