Introduction
Tulisokibart, a TL1A monoclonal antibody, has demonstrated significantly higher rates of clinical remission and endoscopic and histologic improvements vs. placebo in participants with moderately to severely active ulcerative colitis (UC) in the ARTEMIS-UC clinical trial 1. Although histologic remission has been associated with improved long-term outcomes in UC, histology is inconsistently performed and heterogeneously evaluated in routine clinical care as an assessment of remission depth.
Aims & Methods
This analysis of ARTEMIS-UC explores the correlation between changes in clinical, biomarker, endoscopic, and histologic endpoints following tulisokibart treatment over 50 weeks, potentially providing additional accessible indicators of treatment efficacy. ARTEMIS-UC enrolled two cohorts based on a genetic diagnostic test (Dx) for anti-TL1A treatment response: Cohort 1 (participants regardless of Dx results) and Cohort 2 (only Dx positive participants). We examined 15 relationships between five clinical, endoscopic, and biomarker endpoints and three histologic endpoints at Week 12 after induction (Cohort 1) and Week 50 (Cohorts 1 and 2) among induction responders continuing maintenance tulisokibart. Histologic endpoints included histologic improvement, histologic-endoscopic mucosal improvement (HEMI), and mucosal healing (Table) assessed in the Histology Analysis Set (HAS), i.e., participants who received ≥1 dose of study medication and had Geboes scores at both Baseline and Week 12. Clinical/endoscopic/biomarker endpoints included Modified Mayo Score for clinical remission, clinical response, endoscopic improvement, normalization of fecal calprotectin, and hsCRP normalization. The Phi correlation coefficient assessed pairwise correlations between clinical/endoscopic/biomarker and histologic endpoints.
Results
There were 65 and 34 tulisokibart participants included in the HAS population for the Week 12 and Week 50 analyses, respectively. The strongest correlations were the following: endoscopic improvement:HEMI, endoscopic improvement:mucosal healing, clinical remission:HEMI, and clinical remission:mucosal healing, all >0.8 at Week 12 (post-induction in Cohort 1) and >0.9 at Week 50 (post-maintenance dosing in Cohorts 1 and 2). Normalization of fecal calprotectin also demonstrated a strong correlation with histologic endpoints (>0.7) at Week 50 (Table).
Table: Correlation between Clinical and Histologic Endpoints
| Cohort 1 HAS Week 12 | Cohort 1+2 HAS Week 50 |
| Clinical Endpoints | Histologic Improvementa | HEMIb | Mucosal Healingc | Histologic Improvementa | HEMIb | Mucosal Healingc |
| hsCRP Normalization | 0.19 | -0.06 | -0.06 | 0.15 | 0.36 | 0.36 |
| Fecal Calprotectin Normalization | 0.35 | 0.49 | 0.49 | 0.31 | 0.75 | 0.75 |
| Clinical Response | 0.34 | 0.41 | 0.41 | 0.25 | 0.42 | 0.42 |
| Endoscopic Improvement | 0.57 | 0.87* | 0.87* | 0.57 | 0.94** | 0.94** |
| Clinical Remission | 0.60 | 0.85* | 0.85* | 0.61 | 0.94** | 0.94** |
HAS = Histology Analysis Set (participants who received ≥1 dose of study medication and had Geboes scores at both Baseline and Week 12)
Bold = correlation > 0.7; bold and *= correlation > 0.8; bold and ** = correlation > 0.9; higher values indicate greater correlation between endpoints
Correlation is phi correlation for two dichotomized variables
aGeboes score ≤ 3.1; b Geboes score ≤ 3.1 and endoscopy subscore ≤ 1 without friability; c Geboes score ≤ 2B.1 and endoscopy subscore ≤ 1 without friability |
Conclusion
Strong correlations exist between clinical, endoscopic, and histologic endpoints after 12 weeks of induction therapy with tulisokibart, followed by 38 weeks of maintenance therapy in induction responders. These findings underscore the potential for clinical remission to reflect both endoscopic and histologic healing in UC patients, which may enhance patient management strategies and enable a more comprehensive understanding of treatment efficacy. Moreover, these findings indicate the potential of tulisokibart in achieving deep remission2 in patients with ulcerative colitis.
References
1) Sands BE et al. N Engl J Med. 2024 ;391:1119-1129; 2) Lobatón T et al. United European Gastroenterol J. 2018;6:765-772.
Disclosure
The submitting author of an abstract is requested to declare any potential conflict of interest for all authors during the abstract submission. Moreover, the authors’ names (full first names, family names), gender and affiliation (places of work/institution, city, country) must be provided.
CM has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Pendopharm, Pfizer, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD), Roche, Sanofi, Takeda, Tillotts Pharma; speaker’s fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Eli Lilly, Ferring, Fresenius Kabi, Janssen, Organon, Pendopharm, Pfizer, Sanofi, Takeda, Tillotts Pharma; royalties from Springer Publishing; research support from AbbVie, Ferring, Pfizer
RWL discloses advisory board membership: AbbVie, Aspen, BMS, Celgene, Celltrion, Chiesi, Ferring, Glutagen, Hospira, Janssen, Lilly, MSD, Novartis, Pfizer, Takeda; research grant recipient: Celltrion, Shire, Janssen, Takeda, Gastroenterological Society of Australia, NHMRC, Gutsy Group, Pfizer, Joanna Tiddy grant, McKusker Charitable Foundation.
JL reports no financial competing interests
XH reports support from AbbVie, Abivax, Alphasigma, Arena, Cellgen, Gilead, Eli Lilly, Enterome, Janssen, InDex Pharmaceuticals, Pfizer, MSD, Roche, Salix, Sangamo, Takeda, and Theravance for clinical research; consulting fees from AbbVie, Abivax, Arena, Galapagos, Gilead, Janssen, Pfizer, Roche, Sangamo, Takeda, and Viatris; and lecture fees from AbbVie, Abivax, Amgen, Arena, Galapagos, Gilead, Fresenius-Kabi, Janssen, Pfizer, Roche, Sangamo, Takeda, and Mylan.
Brigid S. Boland: BSB has research grants from MSD, Mirador, Gilead as well as serves as a consultant for Abbvie, MSD, Celltrion.
JX, WZ, and MY are employees of MSD.
