Introduction

Ulcerative colitis (UC) is characterized by chronic immune mediated inflammation of the colon and rectum. Prednisolone (PSL) is a common treatment for patients with moderate to severe active UC, but its effect varies among patients, including resistance, response, and dependence. In addition, the longer PSL therapy continues, the greater the concern regarding drug-related side effects. Currently, new immunomodulatory therapies are being developed for the treatment of UC, like carotegrast methyl, a drug showing promise in the treatment of patients with moderate UC refractory to 5-aminosalicylic acid (5-ASA). Thus, the clinical benefit of being able to predict whether certain patients would benefit from PSL therapy prior to administration cannot be overestimated.

Aims & Methods

We compared the clinical characteristics of patients with steroid-resistant (SR) and steroid-non-resistant (SNR) UC and retrospectively evaluated for biomarkers that could predict the efficacy of PSL prior to administration in patients with moderate to severe active UC who failed to respond to 5-ASA.
We enrolled 92 UC patients presenting at Nippon Medical School Hospital with a history of PSL administration prior to March 2022. The patients were divided into two groups, SR patients and NSR patients, and their clinical characteristics were determined according to medical records.

Results

Clinical characteristics of UC patients were as follows: the median age, 48±17 years; height 166±9.2 cm, and weight, 58±14 kg; including 57 males to 35 females. The most common distribution of disease type was the total colitis (63%), followed by left-sided colitis (32%), and proctitis (5%). Complete SR was observed in 15 patients (16%), with remaining 77 patients (84%) classified as SNR. There was no significant difference found in Mayo Endoscopic Score, first dose of PSL, number of hospitalizations, number of relapses, percentage of patients with total-colitis type, or duration of PSL treatment between the SR group and the SNR group. The non-remission rate, defined as failure to achieve mucosal healing, was significantly higher in the SR group (66%) than in the SNR group (36%) (P=0.03). The proportion of patients treated with azathioprine was significantly higher in the SNR group (40%) than in the SR group (39%). The proportion of patients treated with biologics or small molecular compounds was significantly higher in the SR group (40%) than in the SNR group (22%) (P=0.03).
We then compared haematological biomarkers from blood samples obtained prior to PSL administration between the two groups. There was no significant difference in WBC counts, hemoglobin values, serum albumin concentrations, CRP values, and ESR between the two groups. However, eosinophil (both total count number and ratio to white blood cell count) was significantly higher in the SNR group than in the SR group (P=0.02). Neutrophil-lymphocyte ratio tended to be higher in the SNR group than in the SR group (P=0.059). Histological examination revealed that infiltrated eosinophil counts in rectal mucosa biopsied by endoscopy was significantly higher in the SNR group than in the SR group.

Conclusion

Both eosinophil ratios in the blood and rectal mucosa, and neutrophil-lymphocyte ratios in the blood may be potential biomarkers for steroid responsiveness prior to administration.

References

・British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut. 2019; 68: s1–s106
・Severe ulcerative colitis: at what point should we define resistance to steroids?
WJG 2008 Sep 28;14(36):5504-7.
・A reproducible grading scale for histological assessment of inflammation in ulcerative colitis
：Gut 47：404－409，2000
・Mucosal Eosinophil Abundance in Non-Inflamed Colonic Tissue Is Associated with Response to Vedolizumab Induction Therapy in Inflammatory Bowel Disease：J Clin Med Res,2022

Introduction

The efficacy and safety of risankizumab (RZB), an anti-interleukin 23p19 monoclonal antibody, as induction and maintenance therapy for adults with moderately to severely active ulcerative colitis (UC) was recently reported.^1,2 Influences of baseline disease characteristics on clinical outcomes are important to consider when optimizing UC treatment. Herein we analyze the efficacy of RZB stratified by baseline UC disease characteristics.

Aims & Methods

In the 12-week phase 3 INSPIRE induction study (NCT03398148) patients with moderately to severely active UC were randomized 2:1 to receive intravenous (IV) RZB 1200 mg or placebo (PBO) at weeks 0, 4, and 8. Patients with clinical response to RZB IV induction at week 12 or 24 in the phase 2b/3 induction studies were randomized 1:1:1 to receive subcutaneous (SC) RZB 180 mg, RZB 360 mg, or PBO (RZB withdrawal) every 8 weeks in the 52-week phase 3 COMMAND maintenance study (NCT03398135). This post hoc analysis evaluates clinical response, clinical remission, endoscopic remission, endoscopic improvement, and histological-endoscopic mucosal improvement (HEMI) at week 12 and 52 in subgroups stratified by baseline disease characteristics (Adapted Mayo score, pancolitis, high‑sensitivity C‑reactive protein [hs‑CRP], Mayo endoscopic subscore [ES], and disease duration).

Results

The induction analysis included 650 and 325 patients who received RZB 1200 mg IV and PBO IV, respectively. The maintenance analysis included 179, 186, and 183 patients who received RZB 180 mg SC, RZB 360 mg SC, and PBO (RZB withdrawal) SC, respectively. At induction week 12, the proportions of patients receiving RZB 1200 mg IV who achieved clinical response were numerically higher for the following baseline characteristic subgroups: pancolitis absence (70.5%) vs pancolitis presence (58.4%), Mayo ES of 2 (75.5%) vs Mayo ES of 3 (59.0%), and hs-CRP ≤ 5 mg/mL (68.9%) vs hs-CRP > 5 mg/mL (57.3%); the proportions of patients receiving RZB 1200 mg IV who achieved clinical remission at induction week 12 were also numerically higher for subgroups with pancolitis absence (25.3%) vs pancolitis presence (15.6%), Mayo ES of 2 (31.7%) vs Mayo ES of 3 (14.9%), and hs-CRP ≤ 5 mg/mL (23.7%) vs hs-CRP > 5 mg/mL (14.5%; Table). Differences in outcomes were not observed between subgroups stratified by Adapted Mayo score or disease duration. At week 52 of the maintenance study, there was no impact of baseline disease characteristics on achievement of clinical response and clinical remission with RZB (Table).

Conclusion

RZB induction and maintenance therapy improved clinical outcomes, regardless of baseline disease characteristics. Numerically higher RZB induction efficacy was observed for patients with no baseline pancolitis, Mayo ES of 2, and hs‑CRP ≤ 5 mg/L. These trends are consistent with prior observations that patients with milder UC disease phenotypes tend to be more responsive to therapy.

Table. Clinical Response and Clinical Remission by Baseline Disease Characteristics
Subgroup Patients, % (95% CI)	Induction Week 12			Maintenance Week 52
		Clinical Response	Clinical Remission		Clinical Response	Clinical Remission
AMS ≤ 7 > 7	PBO RZB 1200 mg IV PBO RZB 1200 mg IV	31.1 (24.5, 37.6) 63.8 (59.4, 70.7) 42.2 (33.9, 50.6) 65.1 (59.4, 70.7)	8.0 (4.1, 11.9) 22.6 (18.4, 26.8) 3.7 (0.5, 6.9) 17.2 (12.7, 21.7)	PBO RZB 180 mg SC RZB 360 mg SC PBO RZB 180 mg SC RZB 360 mg SC	57.6 (47.5, 67.7) 66.7 (57.5, 75.8) 63.3 (54.3, 72.4) 42.6 (35.9, 56.4) 70.1 (59.9, 80.4) 61.0 (50.1, 71.9)	29.3 (20.0, 38.7) 41.1 (31.5, 50.6) 36.7 (27.6, 45.7) 20.9 (12.5, 29.2) 39.0 (28.1, 49.9) 39.0 (28.1, 49.9)
Pancolitis Yes No	PBO RZB 1200 mg IV PBO RZB 1200 mg IV	32.8 (25.8, 39.7) 58.4 (53.1, 63.7) 39.1 (31.3, 46.9) 70.5 (65.4, 75.5)	6.5 (2.8, 10.1) 15.6 (11.7, 19.5) 6.0 (2.2, 9.7) 25.3 (20.5, 30.1)	PBO RZB 180 mg SC RZB 360 mg SC PBO RZB 180 mg SC RZB 360 mg SC	44.9 (35.1, 54.7) 64.9 (55.2, 74.5) 62.8 (53.0, 72.5) 60.0 (49.3, 70.4) 71.8 (62.2, 81.3) 61.9 (52.0, 71.9)	19.4 (11.6, 27.2) 40.4 (30.5, 50.3) 36.2 (26.5, 45.9) 31.8 (21.9, 41.7) 39.9 (29.4, 50.3) 39.1 (29.2, 49.1)
hs-CRP, mg/L ≤ 5 > 5	PBO RZB 1200 mg IV PBO RZB 1200 mg IV	39.0 (31.8, 46.2) 68.9 (64.3, 73.5) 30.5 (22.9, 38.1) 57.3 (51.1, 63.5)	7.5 (3.6, 11.4) 23.7 (19.4, 27.9) 4.3 (0.9, 7.6) 14.5 (10.1, 18.8)	PBO RZB 180 mg SC RZB 360 mg SC PBO RZB 180 mg SC RZB 360 mg SC	58.5 (48.6, 68.5) 62.2 (52.2, 72.2) 67.5 (59.0, 76.0) 47.1 (36.4, 57.7) 73.6 (64.3, 82.8) 53.7 (41.8, 65.7)	28.7 (19.6, 37.9) 42.2 (32.0, 52.4) 41.9 (32.9, 50.8) 22.4 (13.5, 31.2) 37.8 (27.6, 48.0) 31.3 (20.2, 42.5)
Mayo ES 2 3	PBO RZB 1200 mg IV PBO RZB 1200 mg IV	38.3 (28.5, 48.1) 75.5 (69.6, 81.3) 34.6 (28.5, 40.8) 59.0 (54.4, 63.6)	8.5 (2.9, 14.2) 31.7 (25.4, 38.4) 5.3 (2.4, 8.2) 14.9 (11.6, 18.3)	PBO RZB 180 mg SC RZB 360 mg SC PBO RZB 180 mg SC RZB 360 mg SC	59.6 (46.3, 73.0) 80.9 (69.6, 92.1) 66.7 (55.0, 78.3) 48.9 (40.3, 57.4) 63.6 (55.4, 71.8) 60.1 (51.5, 68.8)	32.7 (19.9, 45.4) 57.4 (43.3, 71.6) 39.7 (27.6, 51.8) 22.1 (15.0, 29.2) 34.0 (25.9, 42.1) 36.6 (28.1, 45.1)
Duration, years < 2 2–5 5–10 > 10	PBO RZB 1200 mg IV PBO RZB 1200 mg IV PBO RZB 1200 mg IV PBO RZB 1200 mg IV	42.9 (29.9, 55.8) 66.0 (57.0, 75.1) 32.5 (22.0, 42.9) 63.4 (56.5, 70.4) 32.3 (23.1, 41.5) 64.9 (58.0, 71.8) 37.6 (27.8, 47.5) 63.4 (56.2, 70.6)	5.4 (0, 11.3) 25.5 (17.2, 33.8) 9.4 (2.8, 16.0) 19.9 (14.2, 25.6) 2.0 (0, 4.8) 21.5 (15.6, 27.4) 8.6 (2.9, 14.3) 16.3 (10.8, 21.8)	PBO RZB 180 mg SC RZB 360 mg SC PBO RZB 180 mg SC RZB 360 mg SC PBO RZB 180 mg SC RZB 360 mg SC PBO RZB 180 mg SC RZB 360 mg SC	60.9 (40.9, 80.8) 70.4 (53.1, 87.6) 75.0 (53.8, 96.2) 35.3 (22.2, 48.4) 59.1 (44.6, 73.6) 66.6 (54.0, 79.2) 60.0 (47.6, 72.4) 76.5 (64.8, 88.1) 50.0 (34.9, 65.1) 55.1 (41.2, 69.0) 66.7 (54.4, 78.9) 63.5 (52.5, 74.5)	26.1 (8.1, 44.0) 55.2 (36.3, 74.1) 37.5 (13.8, 61.2) 17.6 (7.2, 28.1) 38.6 (24.2, 53.0) 40.7 (27.6, 53.8) 36.7 (24.5, 48.9) 51.0 (37.3, 64.7) 31.0 (17.0, 44.9) 18.4 (7.5, 29.2) 24.6 (13.4, 35.7) 39.2 (28.1, 50.3)
AMS, Adapted Mayo score; ES, endoscopic subscore; hs-CRP, high-sensitivity C-reactive protein; IV, intravenous; PBO, placebo; RBS, rectal bleeding subscore; RZB, risankizumab; SC, subcutaneous; SFS, stool frequency subscore. Data are reported using nonresponder imputation while incorporating multiple imputation to handle missing data due to COVID-19 or the geo‑political conflict in Ukraine and surrounding impacted regions. Clinical response is defined as a decrease in AMS that is ≥ 2 points and ≥ 30% from baseline plus a decrease in RBS ≥ 1 or an absolute RBS ≤ 1. Clinical remission is defined as SFS ≤ 1 (and not greater than baseline), RBS = 0, and endoscopic subscore ≤ 1 without evidence of friability.

References

1. Louis E, et al. United Eur Gastroenterol J . 2023;11(S8):26–28. Abstract OP021.
2. Louis E, et al. J Crohns Colitis. 2024;18(S1):i10–12. Abstract OP06.

Disclosure

CH has served as a consultant, advisor, and/or has received education funds from AbbVie, Bausch Health, BMS, the Helmsley Charitable Trust, Janssen, Pfizer, Roivant, and Takeda.
MDL has received consulting fees and/or research grants from AbbVie, BMS, Intercept, Janssen, Lilly, Pfizer, Prometheus, Takeda, and Target RWE.
SRF has served as a consultant or advisor for AbbVie, Janssen, MSD, Takeda, Tillots, and Vitoria.
TF has received research grants and/or speaking honoraria from AbbVie, Ajinomoto, Alfresa, BI, BMS, Celgene, Celltrion, Daiichi Sankyo, EA Pharma, Eisai, Gilead, Janssen, Kissei, Kyorin, Kyowa Hakko Kirin, Lilly, Mebix, Mitsubishi Tanabe, Mochida, Nichiiko, Nippon Kayaku, Pfizer, Sanofi, Taiho, Takeda, and Zeria.
ZR has no disclosures to report.
JK, PL, SC, LC, RV, and PMH are employees of AbbVie and may hold AbbVie stock and/or stock options.
FA-A has served as a consultant and/or has received grants and speaker fees from AbbVie, Celltrion, Kern, MSD, and Takeda.
RA has served as a consultant or advisor for AbbVie, AstraZeneca, BI, Biogen, BMS, CED-Service GmbH, Celltrion, Falk Foundation, Galapagos, Gilead, InDex, Janssen-Cilag, Lilly, MSD, Roche, and Takeda.
Funding
AbbVie funded this study and participated in the study design, research, data collection, analysis, interpretation of data, reviewing, and approval of the abstract. All authors had access to relevant data and participated in the drafting, review, and approval of this abstract. No honoraria or payments were made for authorship. AbbVie and the authors thank all trial investigators and the patients who participated in this clinical trial. Medical writing support was provided by Morgan A Gingerich, PhD, of JB Ashtin, and funded by AbbVie, and Karen Chien, PhD, of AbbVie.

Introduction

A deeper understanding of the pathogenesis of UC has led to the emergence of new therapeutic strategies. One of them consists of targeted exposure with biological drugs to certain molecules that regulate the interaction between leukocytes and endothelial cells in the inflammatory zone (mainly leukocyte integrins and endothelial cell adhesion molecules of the immunoglobulin superfamily).

Aims & Methods

Purpose of the study: To study the content of adhesion molecules ICAM-1, ICAM-2 and L-selectin in the peripheral blood of patients with ulcerative colitis (UC) and the effect of vedolizumab (Intivio) on their levels.
Materials and methods: We examined 12 patients with moderate and severe forms of UC and the ineffectiveness of previous standard therapy. The severity of the UC attack was calculated according to the Mayo index. Antivio® 300 mg was administered to patients intravenously according to the attached instructions. The content of adhesion molecules in the peripheral blood was studied before and 6 weeks after the first injection of vedilizumab. The control group consisted of 15 healthy volunteers. The content of ICAM-1, ICAM-2 and L-selectin in blood serum was determined by multilayer ELISA analysis (Bender med.Systems, Austria). Statistical processing of the obtained results was carried out using SPSS 13.0 software.

Results

It was found that the initial levels of ICAM-1 (461.9±28.4 ng/ml), ICAM-2 (323.3±18.4 ng/ml) and sL-selectin (1650±12.25 U/ml) ) in the peripheral blood of patients with UC were increased (P<0.05 with control), the Mayo index was 9 points. After four infusions of Vedolizumab (week 14), the levels of soluble molecules decreased in 4 patients, with a predominant decrease in sL-selectin (201±9.32 ng/ml, 197±8.54 pg/ml and 1008±15.3 U/ml respectively). The Mayo index was 5 points. In 8 patients, by the 6th week of treatment, the levels of the studied adhesive molecules did not change, although the Mayo index decreased by 3 points.

Conclusion

The initial level of ICAM-1, ICAM-2 and sL-selectin in the peripheral blood of patients with severe forms of UC is increased. The dynamics of the synthesis of adhesive molecules by immunocompetent cells under the influence of the fourth administration of Vedolizumab may predict the possibility of continuing the administration of the drug.

Introduction

Obefazimod is an investigational, oral, once-daily (od), small molecule which enhances expression of microRNA-124 and is currently in phase 3 clinical trials for the treatment of patients with moderately to severely active ulcerative colitis (UC) [1]. Obefazimod demonstrated efficacy and safety in patients with UC at week-8 in a placebo-controlled, Phase 2b induction trial and in the subsequent open-label maintenance (OLM) study [2]. Here we present results for effects of obefazimod induction on histologic and combined histologic and endoscopic outcomes at week 8.

Aims & Methods

Patients with a modified Mayo score of 5-9 and a centrally read Mayo endoscopy subscore ≥2 at induction baseline were randomized 1:1:1:1 to receive either obefazimod 25mg, 50mg or 100mg od or placebo. Rectal or sigmoidal biopsies were collected during endoscopy at baseline and week 8 to evaluate treatment effect on histopathology scores utilizing the Geboes Index. Histologic improvement (Geboes histologic score ≤3.1), and histo-endoscopic mucosal improvement (Geboes histologic score ≤3.1 + Mayo endoscopy subscore of 0 or 1 with no friability; HEMI) were evaluated at week 8.

Results

Of the 252 patients randomized (with a mean age of 41.2 years; 41.3% female; mean UC disease duration of 8.05 years), 188 received obefazimod treatment, and 64 were administered a placebo. Baseline demographics, disease characteristics and histologic activity were consistent across treatment groups. The proportion of patients with histologic improvement at week 8 was 43% among obefazimod-treated patients (all doses) and 31% among those receiving placebo (Table 1). The proportion of patients with endoscopic improvement at week 8 was 35% among obefazimod-treated patients (all doses) and 13% among those receiving placebo. The proportion of obefazimod-treated patients who achieved HEMI at week 8 was greater than placebo-treated patients (27% vs 13%, respectively). Consistently positive histological outcomes were observed when evaluating all three obefazimod induction doses individually compared to placebo (Table 1).

Table 1: Histologic and combined histologic and endoscopic outcomes at week 8

1: Histological improvement: Neutrophil infiltration in <5% of crypts, no crypt destruction, and no erosions, ulcerations or granulation tissue according to the Geboes grading system (ie, Geboes histologic score ≤3.1); 2: Endoscopic improvement: endoscopic sub-score ≤1; 3: Histo-endoscopic mucosal improvement: A combination of histologic improvement (ie, Geboes histologic score ≤ 3.1) and endoscopic improvement (Mayo endoscopy subscore of 0 or 1 with no friability).

Conclusion

In this Phase 2b induction trial, patients with moderately to severely active UC treated with obefazimod experienced clinically meaningful improvements in histologic and combined histologic and endoscopic outcomes at week 8.

References

1. Vermeire S, et al. J Crohns Colitis. 2023; 17: 1689-1697
2. Vermeire S, et al. The Lancet Gastroenterology & Hepatology. 2022; 7: 1024-1035.

Disclosure

Bruce E Sands has served as a consultant or received speaker’s fees from AbbVie, Abivax, Adiso Therapeutics, AgomAb, Alimentiv, Amgen, Arena Pharmaceuticals, Artizan Biosciences, Artugen Therapeutics, AstraZeneca, Bacainn Therapeutics, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Calibr, Celltrion, ClostraBio, Connect Biopharm, Cytoki Pharma, Eli Lilly and Company, Enthera, Evommune, Ferring, Fresenius Kabi, Galapagos, Gilead Sciences, Genentech, Glaxo SmithKline, Gossamer Bio, HMP Acquisition, Imhotex, Immunic, InDex Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Ironwood Pharmaceuticals, Janssen, Johnson & Johnson, Kaleido, Kalyope, Merck, MiroBio, Morphic Therapeutic, MRM Health, OSE Immunotherapeutics, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, RedHill Biopharma, Sun Pharma Global, Surrozen, Synlogic Operating Company, Takeda, Target RWE, Theravance Biopharma R&D, TLL Pharmaceutical, USWM Enterprises, Ventyx Biosciences, Viela Bio, and stock options from Ventyx Biosciences.
Séverine Vermeire has received grants from AbbVie, J&J, Pfizer, Takeda and Galapagos; SV has received consulting and/or speaking fees from: AbbVie, Abivax, AbolerIS Pharma, AgomAb, Alimentiv, Arena Pharmaceuticals, AstraZeneca, Avaxia, BMS, Boehringer Ingelheim, Celgene, CVasThera, Cytoki Pharma, Dr Falk Pharma, Ferring, Galapagos, Genentech-Roche, Gilead, GSK, Hospira, Imidomics, Janssen, J&J, Lilly, Materia Prima, MiroBio, Morphic, MrMHealth, Mundipharma, MSD, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance, Tillots Pharma AG, Zealand Pharma.
Laurent Peyrin-Biroulet has received grants from Celltrion, Fresenius Kabi, Takeda; LPB has served as a consultant or received speaker’s fees from Abbvie, Abivax, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena, Biogen, BMS, Celltrion, Connect Biopharm , Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilea, Gossamer Bio, GSK, Hac Pharm, IAC Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopa, Morphic, MSD, Norgine, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeuthics, Pandion Therapeuthics, Par' Immune, Pfizer, Prometheus, Protagonist, Roche, Roivant, Samsung, Sandoz, Sanofi, Takeda, Theravance, Thermo Fischer, Tigenix, Tillots, Viatris, Vifor, Vectivbio, Ventyx, Ysopia.
Silvio Danese has served as consultant or received speaker’s fees from AbbVie, Ferring, Hospira, Johnson & Johnson, Merck, MSD, Takeda, Mundipharma, Pfizer Inc, Tigenix, UCB Pharma, Vifor, Biogen, Celgene, Allergan, Celltrion, Sandoz, Boehringer Ingelheim.
Parambir Dulai received speaker’s fees from Abbvie, Abivax, Adiso, Bristol Meyer Squibb, Geneoscopy, GSK, Janssen, Lilly, Pfizer, Takeda.
Herbert Tilg has served as a consultant or received speaker’s fees from Abbvie, Abivax, Dr Falk Pharma, ferring, Galapagos, Microbiotica, MSD, Pfizer, Takeda.
Britta Siegmund has served as consultant for Abbvie, Abivax, Arena, BMS, Boehringer, CED Service GmbH, Celgene, CT Scout, Endpoint Health, Falk, Forga Software, Galapagos, Janssen, Lilly, Materia Prima, Pfizer, Takeda, Pharma Insight, Predictimmune, PsiCro; Speaker fees: AbbVie, BMS, CED Service GmbH, Chiesi, Falk, Ferring, Gilead, Janssen, Lilly, Materia Prima, Takeda, Pfizer and grant support by Arena/Pfizer (served as representative of the Charité).

Introduction

Data on using Intestinal Ultrasonography (IUS) for monitoring colonic lesions and treatment response in ulcerative colitis (UC) are still limited and most results are from single-center units usually performed in centers with a special expertise in IUS.

Aims & Methods

Our multicenter study aimed to identify predictive factors and monitor early response after different therapies in UC.
Methods: From July 2022 to Oct. 2023, we conducted a multicenter study at 5 IBD centers. UC pts starting biological therapies or small molecules were included, and underwent colonoscopy (CS), IUS, clinical assessments at baseline and at 12 weeks. All pts received standard of care therapy according to ECCO guidelines. Exclusion criteria were disease limited to the rectum, active infections, and inability or contraindication to perform CS and/or IUS within the time intervals established by the study. Colonic wall thickening (CWT), vascularization (CWF), Milan Ultrasound Criteria (MUC), Mayo endoscopic score (MES), total/partial Mayo score were evaluated.

Results

Eighty-four UC patients were enrolled and eligible for starting biological therapy or small molecules. Forty-nine out of 84 pts (58.4%) were male, 40 pts (47.6%) had extensive colitis and 44 pts (52.4%) had left colitis, with a disease duration of 20 months (1-336); 53 pts (63%) were steroid-dependent/refractory. Forty-one pts (48.9%) started anti-TNFs, 14 pts (16.6%) anti-IL12/23 or anti IL 23, 16 pts (19%) vedolizumab, and 13 pts (15.5%) JAKi. After 12 weeks, 39 out of 84 patients (46.4%) had partial Mayo score<2, 31 patients (36.9%) 2-4, 10 patients (11.9%) 5-7, and 4 patients (4.76%) >7. Forty-three out of 84 patients (51.2%) had MES=0-1, while 41 out of 84 patients (48.8%) had MES=2-3. Fifteen out of 84 patients (17.9%) had ultrasonographic response (defined as CWT<3mm) and 26 out of 84 patients (30.1%) had MUC<6.2 (1). Logistic regression was performed to evaluate the relationship between clinical/endoscopic and ultrasonographic characteristics and early IUS response at 3 months. Univariable analysis showed that active smoking ([RR], 1.9; 95% CI, 1.2–3.1, p<0.005), appendectomy ([RR], 2.5; 95% CI, 1.9–3.2, p<0.0001), partial Mayo score <2 ([RR], 2.18; 95% CI, 1.5–3, p<0.001) were associated with higher risk of response at 3 months. Inversely, severe endoscopic lesions (MES 3) (RR, 0.3; 95% CI, 0.2–0.6; p<0.0001), presence of lymph-nodes, mesenteric hypertrophy and vascularization (p<0.001, RR 0.36, 0.28, 0.45 respectively) were associated with a lower risk of response at 3 months. CWT was associated with a lower risk of response at 3 months (RR 0.66, 95% CI, 0.53-0.81, p<0.0001) and every increased mm was associated with a 34% reduction of IUS response. MUC was associated with a lower risk of response at 3 months (RR 0.78, 95% CI, 0.7-0.87) and every increased of one point was associated with a 22% reduction of IUS response. In the multivariable analysis, CWT and MUC were the only predictive factors associated with IUS response at 3 months (RR 0.70, 0.78 respectively, p<0.04). A CWT<5.5 mm showed a 2.5 risk of treatment response at 3 months.

Conclusion

Our multicenter study demonstrated that IUS allows close monitoring of treatment in UC. MUC, and in particular CWT, are valuable parameters to predict early response in UC.

References

1)Allocca M, et al. Predictive value of Milan ultrasound criteria in ulcerative colitis: a prospective observational cohort study. United European Gastroenterol J. 2022; 10:190-7.