Introduction

Biologic agents have emerged as the most important therapeutic weapon in the treatment of Crohn's disease, but there are few data in the literature comparing the efficacy and safety between different molecules. The aim of this study is to describe the population of patients who received different molecules as first-line therapy and their persistence on first-line therapy.

Aims & Methods

622 patients from 6 Gastroenterology departments from Bucharest, Iasi and Cluj treated between 2006 and 2024 were included in the study. 75 (14%) were excluded because they received only Mesalazine. 535 were included in the final analysis. The main outcomes were: clinical response at 12 weeks of treatment (complete response = clinical remission, partial response= decrease of CDAI ≥ 25% of the initial value without remission or primary non-response), persistence on therapy and serious adverse events leading to therapy discontinuation.

Results

The main characteristics of the studied patients are shown in the table 1. There are significant differences between the 3 groups of patients: regarding age, extension of the disease, disease phenotype, proportion of individuals with perianal fistulas, clinical severity of the disease, proportion of operated patients. Median therapy duration was 48 months (3÷330). 45% of patients received Adalimumab, 40% were treated with Infliximab, and in 13% Ustekinumab was given. The 3 biologics studied (Adalimumab/Infliximab/Ustekinumab) had a similar rate of complete response 80%, the non-response rate was also similar: 6.5% but persistence on therapy at 2 years was better for Ustekinumab (64%) compared to Adalimumab and Infliximab (45%) (p=0.03). Serious adverse events leading to therapy discontinuation were more frequent in those treated with Infliximab (10%) compared to Adalimumab (3%) and Ustekinumab (6%) (p=NS).

Conclusion

Patients that received anti-TNF alpha antibodies had more severe forms of Crohn’s disease. All three biological agents used in real life for Crohn’s disease therapy show similar efficacy, with a complete response rate of aprox. 80% and a nonresponse rate of 6.5%, but persistence on therapy at 2 years was significantly better for Ustekinumab (64%) compared to Adalimumab and Infliximab (45%) (p=0.03). Serious adverse events leading to therapy discontinuation were more frequent in patients treated with Infliximab (10%) compared to those who received Ustekinumab (6%) or Adalimumab (3%).

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

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.

Introduction

Perianal Crohn’s disease (pCD) represents a challenging phenotype of Crohn's disease (CD). While risankizumab (RZB) has demonstrated efficacy in luminal CD, its role in pCD remains unknown. We aimed to evaluate the effectiveness of RZB in pCD and compare the outcomes with other biologics including anti-TNF, ustekinumab (UST), and vedolizumab (VDZ).

Aims & Methods

This retrospective multicenter study performed at nine international centers included adult patients with pCD who initiated RZB as advanced-line (second or more) therapy between 2020 and 2024. Historical controls included pairwise propensity-scored matched pCD patients treated with anti-TNF, UST, or VDZ as second- or third-line therapies. The primary outcome was clinical remission in patients with active pCD, defined as complete resolution of perianal symptoms. Secondary outcomes included clinical response (any symptomatic improvement) in active perianal disease, and relapse rates among patients with inactive pCD at baseline, defined as new or recurrent signs or symptoms of perianal disease.

Results

A total of 214 patients with active pCD were included: 59 (27.6%) received RZB, 62 (29.0%) anti-TNF, 57 (26.6%) UST, and 36 (16.8%) VDZ. Clinical remission was achieved in 58% of patients treated with RZB, compared to 32.9% of those receiving non-RZB therapies (p = 0.01), including 27% for anti-TNF, 44% for UST, and 25% for VDZ. Clinical pCD response rates were 81% for RZB, compared to 71% for anti-TNF, 88% for UST, and 44% for VDZ; p < 0.001. In propensity score–matched comparisons, remission rates with RZB were numerically higher than anti-TNF (56% vs. 31%, p = 0.056) and VDZ (58% vs. 29%, p = 0.08), and comparable to UST (53% vs. 43%, p = 0.5). The median time to clinical response with RZB was three months [IQR: 2–3.5], comparable to anti-TNF (3 [IQR: 2–4], p = 0.4), but significantly shorter than UST (5 [IQR: 4–6], p < 0.001) and VDZ (6.5 [IQR: 4–8], p < 0.001).
Among 160 patients with inactive pCD at baseline, matched analysis showed significantly lower relapse rates with RZB compared to anti-TNF (2% vs. 22%, p = 0.004) and VDZ (0% vs. 28%, p = 0.004), with no significant difference compared to UST (3% vs. 15%, p = 0.2).

Conclusion

Risankizumab demonstrates favorable clinical response, faster time to response, and higher remission rates in active pCD, along with the lowest relapse rates in inactive disease. These results support RZB as an effective therapeutic option for pCD, warranting prospective validation.

Disclosure

No conflicts of interest were declared in relation to this study.