etrolizumab (RG7413) / Roche - LARVOL DELTA

Etrolizumab as Induction and Maintenance Therapy in Patients With Moderately to Severely Active Ulcerative Colitis: A Systematic Review and Meta-Analysis (ACG 2025) - "Out of 354 articles screened, only 5 were eligible, with a total of 1808 patients. Etrolizumab had a significant clinical response compared to placebo with an odds ratio of 1.60 [CI:1.23 to 2.09, p < 0.001]. Clinical remission was evaluated in both the induction and maintenance groups, and it was significantly higher in the induction group with an odds ratio of 2.85 [CI: 1.63 to 4.99, p < 0.001]."

Retrospective data • Review • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

From Cytokines to Biomarkers: Mapping the Immunopathology of Inflammatory Bowel Disease. (PubMed, Cells) - "New classes of medications with more favorable side effect profiles include anti-integrin antibodies, vedolizumab, etrolizumab, and carotegrast methyl. Additionally, fecal microbiota transplant (FMT) is a newer area of research for treatment of IBD along with TNF-blockers, JAK inhibitors, and S1PR modulators. However, expense and long preparation time have limited the usefulness of FMT."

Biomarker • IO biomarker • Journal • Review • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Transplantation • Ulcerative Colitis • ATG16L1 • CARD9 • CTLA4 • MMP9 • MPO

LEVERAGING GLOBAL VIDEO CONTEXT TO AUTOMATE COLON SECTION IDENTIFICATION IN ULCERATIVE COLITIS ENDOSCOPY (UEGW 2025) - "Aims & We used the same five phase-III etrolizumab clinical trial datasets underlying UC-SCALE: three trials (3028 videos, 1309 patients, 391 sites) for training, one trial (692 videos, 327 patients, 80 sites) for validation, and one trial (607 videos, 317 patients, 83 sites) for testing... Incorporating video-wide context remarkably enhances frame-by-frame anatomical labeling of UC colonoscopy. This approach can be coupled with UC-SCALE's section-level severity scoring to automate both localization and disease severity estimation, reducing the need for manual section annotation. Future work will validate performance across diverse datasets, potentially lowering trial costs and broadening clinical adoption of IBD AI-based algorithms."

Clinical • Video • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

REAL-WORLD EVIDENCE VALIDATES AI-BASED ENDOSCOPIC SCORING FOR ULCERATIVE COLITIS (UEGW 2025) - "It was trained on a large subset of Phase III Etrolizumab (ETRO) clinical trial data from 471 sites... Applying the original ETRO-trained UC-SCALE model to a real-world UC cohort confirmed its high accuracy and reliability for objective MCES scoring outside of clinical trials. To date, our analysis has focused on predictions at the level of anatomical segments. Future work will expand toward full video-level scoring (closer to clinical workflows) and artificial segments, which offer a more granular topological severity map."

Clinical • HEOR • Real-world • Real-world evidence • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Factors Impacting the Immunogenicity of Etrolizumab & Clinical Consequences. (PubMed, AAPS J) - "However, there was minimal impact of ADA on clinical parameters, such as pharmacokinetics (PK), safety, and efficacy. The findings enhance our understanding of etrolizumab immunogenicity, in the context of clinical impact, providing insights that may inform future biologic development strategies and patient selection criteria in IBD clinical trials."

Journal • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • HLA-DQA1 • HLA-DQB1

Population Pharmacokinetics and Exposure-Response Relationships of Etrolizumab in Patients with Moderately-to-Severely Active Crohn's Disease. (PubMed, J Clin Pharmacol) - "For all induction ER endpoints, tumor necrosis factor (TNF)-naive patients had significantly higher probability of a favorable outcome at end of induction compared to TNF-experienced patients. In summary, exposure-response was more evident at end of maintenance than at end of induction."

Journal • PK/PD data • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Oncology • Ulcerative Colitis • CRP • TNFA

SYMPTOM RESPONSE TRAJECTORY ANALYSIS IDENTIFIES DISTINCT SUBPOPULATIONS IN MODERATE-TO-SEVERE ULCERATIVE COLITIS LINKED TO MAINTENANCE OUTCOMES: A PATIENT LEVEL POST-HOC ANALYSIS OF 2,378 PARTICIPANTS ACROSS 6 RCT'S WITH 8 ADVANCED THERAPIES (DDW 2025) - "Posthoc analysis of the SELECTION trial (filgotinib) demonstrated that analysis of daily PRO2 scores (stool frequency/rectal bleeding) as time-series data reveals discrete subpopulations...Methods In a cross-industry/academia collaboration, data from 2,378 UC participants from RCTs of adalimumab, brepocitinib, etrasimod, etrolizumab, ozanimod, ritlecitinib, ustekinumab, and vedolizumab in UC were analyzed for PRO2-based treatment symptom response trajectories using group-based trajectory modeling (GBTM)...Symptom response trajectories may reflect underlying heterogeneity in individual disease biology in interaction with different MOA (i.e. endotypes). RNASeq analysis of transcriptome regulation in these patients aims to further explore this hypothesis."

Clinical • Metastases • Retrospective data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Gut-directed therapeutics in inflammatory bowel disease. (PubMed, Curr Opin Gastroenterol) - "Gut-targeted therapies range from novel variations on traditional drugs (i.e., mAbs and small molecules) to microbiome-based therapeutics and engineered delivery systems. They can be used alone or in combination with currently available therapies. Future directions should focus on the development of tried-and-true modalities (mAbs, small molecules) as well as the microbiome and more innovative delivery systems."

Journal • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Gene Therapies • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

Clinical response trajectories identify distinct subpopulations of ulcerative colitis patients and are linked to disease outcome across different therapy classes. Patient level analysis of 2378 participants from 6 randomized controlled trials in moderate-severe UC representing 8 different mechanisms of action. (ECCO-IBD 2025) - "Post hoc analysis of the SELECTION trial (filgotinib) demonstrated that treating daily PRO2 scores (stool frequency, rectal bleeding) as time-series data reveals discrete subpopulations.Patients with in the faster response trajectory groups achieve wk52 endpoints at higher rates including disease control. Methods In a cross-industry/academic collaboration, data from 2,378 UC responders from RCTs of adalimumab, brepocitinib, etrasimod, etrolizumab, ozanimod, ritlecitinib, ustekinumab, and vedolizumab in UC were analyzed for PRO2-based treatment response trajectories using Group-based trajectory modeling (GBTM)...Response trajectories likely reflect underlying heterogeneity in disease biology in the interaction with the different MOA (i.e. endotypes). RNASeq analysis of transcriptome regulation in these patients aims to further explore this hypothesis."

Clinical • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Paediatric Inflammatory Bowel Diseases: novel agents on the therapeutic horizon (ECCO-IBD 2025) - "These include etrolizumab, golimumab, guselkumab, mirikizumab, risankizumab, ustekinumab, and vedolizumab. Sixteen trials are recruiting, examining small molecule therapies in pediatrics, to include upadacitinib, tofacitinib, etrasimod, and ozanimod...Consideration for novel trial designs and collaboration between research networks could reduce the delay in paediatric marketing approvals. Continued engagement with regulatory bodies and the international pIBD community offers a critical opportunity to advance drug approvals in children with IBD."

Immunology • Inflammation • Inflammatory Bowel Disease

A Network Meta-analysis to Compare the Efficacy of Advanced Treatments for Biological-Experienced Patients with Ulcerative Colitis (ECCO-IBD 2025) - "Results For induction of remission, Vedolizumab (RR 2.22, 1.02–4.84), Filgotinib (RR 2.47, 1.07–5.70), Risankizumab (RR 2.77, 1.24–6.18), Etrolizumab (RR 2.93, 1.29–6.65), Upadacitinib (RR 4.82, 2.74–8.48) Etrasimod (RR 5.24, 1.20–22.87), Tulisokibart (RR 9.00, 1.20–67.45), Ustekinumab (RR 9.76, 2.36–40.27), and Tofacitinib (RR 10.23, 2.04–51.38) were significantly better than placebo. Tofacitinib (RR 6.56, 1.05–40.85 and RR 6.11, 1.09–34.05), Ustekinumab (RR 6.25, 1.19–32.86 and RR 5.83, 1.26–27.04), and Upadacitinib (RR 3.09, 1.10–8.66 and RR 2.88, 1.27–6.51) were significantly better than both Adalimumab and Mirikizumab, respectively for induction of remission...Based on an analysis of the SUCRA plot, Upadacitinib was the best therapy, followed by Vedolizumab, Etrasimod, Filgotinib, and Mirikizumab. Conclusion In this network meta-analysis, JAK inhibitors (JAKIs) were superior to other therapies for induction as well as maintenance of remission. While Tofacitinib had..."

Metastases • Retrospective data • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Patient endotypes in ulcerative colitis revealed by longitudinal symptom trajectories under therapy (ECCO-IBD 2025) - "Methods Using a reverse translation approach, this study analyses longitudinal data from the etrolizumab phase 3 trials to gain insights into the UC patient population...These symptom patterns show strong concordance with endoscopic, laboratory, and molecular remission profiles. This approach aligns with the principles of personalised medicine by enabling i) dynamic symptom monitoring ii) application in Phase II trials to guide drug development by assessing if a patient is on the right path toward therapeutic success and iii) identification of novel therapeutic targets."

Clinical • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • CRP

ADSS: A novel AI-derived metric for quantifying disease severity and extent in ulcerative colitis (ECCO-IBD 2025) - "Methods UC-SCALE was trained using 4,306 sigmoidoscopy videos from phase III etrolizumab clinical trials and consists of 1) preprocessing algorithms, 2) scoring algorithm that assigns MES score (0-3) to each frame, and 3) camera localization algorithm which maps each frame to an anatomical location...Conclusion UC-SCALE and ADSS provide a holistic disease evaluation by capturing both the severity and extent of inflammation. Together, these tools can be employed to improve the sensitivity of treatment response evaluation in clinical trials."

Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Histology-derived cell-cell interaction networks, linked to transcriptome profiling, define path to resolution in UC (ECCO-IBD 2025) - "We applied machine learning-based approaches to whole scanned images (WSI) of H&E stained slides prepared from formalin-fixed, paraffin embedded intestinal mucosal biopsies from the etrolizumab clinical trials, aiming to identify cellular interactions and molecular signatures that define disease subtypes and treatment responses...Conclusion This study introduces a novel feature engineering approach to unravel the cellular and molecular complexity of WSI in UC. The findings underscore the significance of cellular interactions in UC pathology and provide new insights into the molecular mechanisms underlying different disease states and demonstrates that the structural topology (form) derived from WSI can be effectively linked to the transcriptomic profiles (function) to define probability of remission."

Inflammatory Bowel Disease

Pharmacokinetic analysis using single dilution assays: enhancing precision, reducing errors and increasing throughput. (PubMed, Bioanalysis) - "This enabled assessment of all clinical samples across different concentrations with a single dilution, yielding results with good correlation to ELISA and Gyrolab. NULISA technology offers high sensitivity, full automation, and a wide dynamic range, streamlining assay development and optimization, simplifying sample analysis, minimizing errors, and increasing throughput."

Journal • PK/PD data

Ulcerative Colitis Severity Classification and Localised Extent (UC-SCALE): An Artificial Intelligence scoring system for a spatial assessment of disease severity in Ulcerative Colitis. (PubMed, J Crohns Colitis) - "Our fully-automated scoring system enables accurate, objective and localised assessment of endoscopic severity in UC patients. Additionally, we provide a topological representation of the score as a marker of disease severity that correlates highly with clinical metrics. UC-SCALE reproduces central reading and holds promise to enhance disease severity evaluation in both clinical trials and everyday practice."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

Vagal innervation limits brain injury by inhibiting gut-selective integrin-mediated intestinal immunocyte migration in intracerebral hemorrhage. (PubMed, Theranostics) - "The implication of α4β7 and αEβ7 integrins in this setting was supported by the ineffective influence of α7nAChR agonists on the trafficking of intestinal immunocytes enhanced by administering beta-7 integrin antagonists, such as etrolizumab... The identification of vagus nerve-mediated modulation of α4β7 and αEβ7 integrin expression in the trafficking of immune cells within the intestinal tract holds significant implications. This discovery presents new opportunities for developing therapeutic interventions for ICH and stimulates further investigation in this area."

Journal • Cerebral Hemorrhage • CNS Disorders • Gastrointestinal Disorder • Hematological Disorders • Vascular Neurology

Efficacy of Etrolizumab in Inducing and Maintaining Remission in Ulcerative Colitis: A Comprehensive Meta-Analysis (ACG 2024) - "The analysis revealed a significant increase in the likelihood of achieving clinical remission during the induction phase with etrolizumab (pooled odds ratio [OR]: 3.25, 95% confidence interval [CI]: 1.10–9.65, p < 0.03) and a trend towards improvement in the maintenance phase (pooled OR: 1.43, 95% CI: 0.91–2.23, p < 0.12). These findings suggest substantial potential for Etrolizumab to improve outcomes by reducing mucosal inflammation and promoting sustained remission. Etrolizumab demonstrates substantial efficacy in inducing remission in patients with moderate to severe UC, positioning it as a promising option for initial treatment."

Retrospective data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Mucositis • Ulcerative Colitis

Efficacy and Safety of Etrolizumab in the Treatment of Moderate to Severe Ulcerative Colitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (ACG 2024) - "Five RCTs with a total of 1120 patients were included (Table 1). Etrolizumab was associated with a significantly increased clinical response (RR: 1.60, 95% CI [1.19, 2.14], P = 0.002) and clinical remission rates during both induction (RR: 1.83, 95% CI [1.39, 2.41], P < 0.0001) and maintenance phases (RR: 2.66, 95% CI [1.69, 4.19], P < 0.0001) (Figure-1). It also improved endoscopic outcomes, including endoscopic improvement (induction: RR: 1.55, 95% CI [1.29, 1.87], P < 0.0001; maintenance: RR: 1.69, 95% CI [1.24, 2.30], P = 0.0008) and endoscopic remission (induction: RR: 2.07, 95% CI [1.54, 2.80], P < 0.0001; maintenance: RR: 1.92, 95% CI [1.29, 2.85], P = 0.001), along with histological remission rates (induction: RR: 1.73, 95% CI [1.37, 2.17], P < 0.00001; maintenance: RR: 2.04, 95% CI [1.40, 2.98], P = 0.0002)."

Retrospective data • Review • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Efficacy and Safety of Etrolizumab in the Treatment of Moderate to Severe Ulcerative Colitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. (PubMed, Am J Ther) - No abstract available

Clinical • Journal • Retrospective data • Review • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Evaluation of low volume sampling devices for a pharmacodynamic biomarker analysis: Challenges and solutions. (PubMed, J Pharm Biomed Anal) - "This validated assay was implemented in a proof-of-concept study to compare three low volume sampling devices (Mitra, Tasso-M20 and TassoOne Plus) with serum collected via venipuncture from healthy volunteers receiving etrolizumab...However, a bias was observed in Mitra dried blood samples, presumably due to the different sample collection sites in comparison with venipuncture and Tasso devices. Our study highlights the potential of low volume sampling technologies for biomarker analysis, and underscores the importance of understanding the challenges and limitations of these technologies before integrating them into clinical studies."

Biomarker • Journal • PK/PD data

Efficacy and safety of etrolizumab in the treatment of inflammatory bowel disease: a meta-analysis. (PubMed, PeerJ) - "Endoscopic alleviate (RR = 2.10, 95% CI [1.56-2.82]), endoscopic improvement (RR = 2.10, 95% CI [1.56-2.82]), endoscopic remission (RR = 2.10, 95% CI [1.56-2.82]), Endoscopic improvement (RR = 1.56, 95% CI [1.30-1.89]), histological remission (RR = 1.62, 95% CI [1.26-2.08]), and did not increase any adverse events (RR = 0.95, 95% CI [0.90-1.01]) and serious adverse events (RR = 0.94, 95% CI [0.68-1.31]). According to our current study, etrolizumab is a promising drug in IBD."

Clinical • Journal • Retrospective data • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

Old and New Biologics and Small Molecules in Inflammatory Bowel Disease: Anti Integrins (PubMed, Korean J Gastroenterol) - "Etrolizumab (anti-β7) blocks leukocyte trafficking via α4β7 and cell adhesion via αEβ7 integrins. In addition, the introduction of subcutaneous vedolizumab showed similar efficacy and safety with improved patients' convenience. Other investigational anti-integrin therapies include abrilumab (anti-α4β7 IgG2), PN-943 (orally administered and gut-restricted α4β7 antagonist peptide), AJM300 (orally active small molecule inhibitor of α4), and ontamalimab (anti-MAdCAM-1 IgG)."

Journal • Review • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Oncology • Ulcerative Colitis • TNFA

[PREPRINT] Molecular characterization of response to etrolizumab and anti-TNF reveals treatment resistance in ulcerative colitis is associated with the abundance of residual neutrophil subsets and inflammatory fibroblast populations (bioRxiv) - "Pseudo-time trajectory analyses identified four unique neutrophil subsets with unique cell phenotypes reflecting changes in cell state or differentiation from PADI4hi, OSMhi, MX1hi, ultimately to CXCR4hi populations. PADI4hi and OSMhi neutrophils exhibited high levels of proteases (MMP9, LYZ), inflammatory cytokines (CXCL1, IL1B, OSM), and abundant cytokine or chemokine receptors (CXCR1, CXCR2). MX1 populations expressed markers indicating prior IFN exposure (MX1, IFIT1). In contrast, more differentiated or mature neutrophils exhibited high levels of CXCL2, TNF-a, CXCR4, as well as angiogenic factors like VEGFA. PADI4hi and OSMhi neutrophils we predict have abundant cytokine and chemokine interactions with inflammatory fibroblasts within the inflamed colon such as OSM: OSMR and IL1B: IL1R1 interactions. Changes in PADI4hi and OSMhi neutrophils were closely associated with MCS remission in both etrolizumab and adalimumab-treated patients..."

Clinical data • Preprint • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Gut microbial species and endotypes associate with remission in ulcerative colitis patients treated with anti-TNF or anti-integrin therapy. (PubMed, J Crohns Colitis) - "In this large study of ulcerative colitis patients, we show that few individual species associate strongly with clinical remission, but multivariate models including microbiome can predict clinical remission and have better predictive power compared to clinical data alone."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis