Introduction

Inflammatory bowel disease is a chronic, relapsing condition influenced by genetic, microbial, and environmental factors. This study evaluated the therapeutic potential of multi-strain probiotics in mitigating the severity of experimentally induced colitis in rats, focusing on clinical outcomes, histopathological changes, inflammatory markers, and microbiota changes.

Aims & Methods

Thirty six-week-old male Sprague-Dawley rats were randomly assigned to three groups: Control, Acute Colitis (AC), and Probiotic Treatment (RP; receiving Lactobacillus rhamnosus and Lactobacillus paracasei). Probiotics were administered orally once daily, beginning three days prior to colitis induction with rectal DNBS and continued for seven days post-induction. On day eight, colon tissues and blood samples were collected for histological and biochemical analysis, and fecal samples were analyzed to assess gut microbiota composition.

Results

The AC group showed significantly elevated TNF-α levels compared to the Control and RP groups (p < 0.001), while probiotic treatment significantly reduced TNF-α levels compared to the AC group (p = 0.002, p < 0.001, respectively). Although the RP group demonstrated increased IL-10 levels and decreased MDA levels, these changes were not statistically significant. Histopathological analysis revealed a lower median Ameho’s score in the RP group compared to the AC group, though without statistical significance.

Microbiota analysis showed no significant differences in alpha diversity across groups. However, beta diversity significantly differed in the AC group compared to Control, and after probiotic treatment, the RP group’s beta diversity showed a partial shift toward the Control group. Distinct microbial species characterized each group: Akkermansia spp. and Parasutterella spp. were predominant in distinguishing the Control group from others; Romboutsia spp. and Turicibacter spp. differentiated the AC group; and Roseburia spp. and Anaerotruncus spp. were the key species distinguishing the RP group from the others.

Conclusion

Multi-strain probiotics reduced TNF-α levels and modulated gut microbiota composition in DNBS-induced colitis. Although changes in IL-10, MDA, and histopathology were not statistically significant, trends favored the probiotic group. Microbial analysis revealed distinct species profiles across groups, with partial restoration of beta diversity and enrichment of beneficial taxa like Roseburia spp. in the probiotic group. These findings support the potential of probiotics as a therapeutic adjunct in IBD, highlighting the need for further studies to confirm efficacy and explore underlying mechanisms.

Introduction

Vedolizumab (VDZ), a monoclonal antibody therapy approved for moderate-to-severe ulcerative colitis (UC) and Crohn’s disease (CD) in China in 2020¹ has a unique, gut-selective, anti-lymphocyte trafficking (GSALT) mechanism of action.² However, there is limited data on VDZ's real-world effectiveness and safety in Chinese IBD patients.³ Interim results from the VALUE study that enrolled patients with UC have been published ^3,4 and final results are reported here.

Aims & Methods

VALUE (NCT04872491), a multicenter, single-arm, prospective, observational study evaluated the safety and effectiveness of VDZ in adult Chinese patients with IBD (N = 500) over 72 weeks. Clinical response, clinical remission, and endoscopic remission were assessed at Weeks 14, 30, and 54. Partial Mayo and Mayo endoscopic subscores at baseline and Weeks 14, 30, and 54 were calculated. Clinical response was defined as ≥2-point reduction in Partial Mayo Clinic score and ≥25% decrease from baseline score accompanied with ≥1-point decrease in the rectal bleeding or absolute rectal bleeding subscore ≤1. Clinical remission was defined as Partial Mayo Clinic score ≤2 with no subscore >1, endoscopic remission as Mayo endoscopic subscore ≤1, and complete endoscopic remission as Mayo endoscopic subscore 0. Safety results and CD patients’ data are presented in separate VALUE abstracts (IDs: AS-UEG-2025-01329 and AS-UEG-2025-01324).

Results

Among 409 UC patients enrolled in the final analysis, 91.9% (376/409) were included in the effectiveness analysis set. Mean age (±standard deviation [SD]) of patients was 46.3 (±15.1) years, and 59.4% (n=243) were male. At baseline, 30.8% (126/409) of patients had moderate UC, and 29.8% (122/409) had severe UC. The median duration of UC was 2.5 years, concomitant steroids were prescribed in 18.9% (71/376). Mean (±SD) partial Mayo score was 5.1 (2.1) at baseline, which declined to 1.7 (1.7), 1.5 (1.7) and 1.3 (1.5) by Weeks 14, 30 and 54, respectively, post-VDZ treatment. Patients achieving clinical response, clinical remission, endoscopic remission, and complete endoscopic remission were 76.9% (220/286), 71.1% (207/291), 63.6% (35/55), and 21.8% (12/55) at Week 14; 78.1% (193/247), 76.3% (190/249), 63.6% (28/44), and 27.3% (12/44) at Week 30; and 80.3% (155/193), 83.3% (165/198), 71.4% (20/28), and 50.0% (14/28) at Week 54, respectively. Patients with moderate and severe UC; biologic naïve patients and patients with prior exposure to biologics at baseline also achieved clinical response, clinical remission, and endoscopic remission (Table). Compared with baseline, mean (±SD) reduction of C-reactive protein (mg/L) at Weeks 14, 30, and 54 were 7.8 (20.2), 6.5 (22.2), and 3.4 (24.8), respectively; mean (±SD) reduction of fecal calprotectin (mu g/g) was 42.7 (150.7) at Week 14 and 212.6 (480.1) at Week 30. The proportion of patients achieving clinical remission without steroid use by Week 14 was 37.7% (23/61), which increased to 60.6% (20/33) by Week 54.

Conclusion

This study indicated that VDZ demonstrated a good effectiveness profile in Chinese UC patients in the real-world setting.

References

1. Yan J et al., Medicine (Baltimore). 2024; 103: e38759.
2. Soler D et al. J Pharmacol Exp Ther. 2009; 330: 864-875.
3. Baili C et al. Am J Gastroenterol. 2023; 118: S213-S214.
4. Yan C et al. Am J Gastroenterol. 2023; 119: S894-S895.

Disclosure

This study was funded by Takeda (China) International Trading Co. Ltd. Xiuli Zuo, Ye Chen, and Yingchao Li have no conflicts of interest. Lifei Gu and Fang Zhou are Takeda employees and hold Takeda stock options. Minhu Chen received speaker honorariums from Takeda China, AstraZeneca China, Xian Janssen, and Eisai China.
Medical writing support for the development of this abstract under the direction of the authors was provided by Vibhuti Singh, Ph.D., of Cactus Life Sciences (part of Cactus Communications), funded by Takeda (China) International Trading Co., Ltd.

Introduction

The STRIDE-II consensus on the management of Crohn’s disease (CD) highlights the importance of achieving multiple treatment targets, including clinical remission, normalisation of the inflammatory biomarkers high-sensitivity C-reactive protein (hs-CRP) and fecal calprotectin (FCP), and quality of life (QoL) improvements.¹ In this post hoc analysis of the SEQUENCE open-label extension (OLE), we assessed inflammatory biomarker reductions and improvements in clinical and QoL outcomes (alone or in combination) in patients (pts) with moderately to severely active CD treated with risankizumab (RZB), an interleukin-23 p19 inhibitor.

Aims & Methods

In Part 2 of SEQUENCE (NCT04524611), pts randomised to the RZB arm during Part 1 and who completed the week (wk) 48 visit were eligible to continue receiving open-label 360mg subcutaneous RZB maintenance dose every 8 wks.² This analysis included all patients who completed wk100 of RZB treatment or who discontinued treatment prior to wk100 in Part 2 (cutoff date: July 11, 2024). Pts with elevated hs-CRP (> 5 mg/L) or FCP (> 250 mg/kg) at induction baseline were assessed for achievement of normalised hs-CRP or FCP alone or in combination with clinical remission per CD activity index (CDAI) or per stool frequency/abdominal pain score (SF/APS), or with inflammatory bowel disease questionnaire (IBDQ) remission (endpoints defined in Table footnote) at wks 52 (OLE baseline), 76, and 100. Data were assessed for all intent-to-treat pts using as observed (AO) regardless of rescue therapy and nonresponder imputation (NRI). Safety was previously reported and not assessed in this post hoc analysis.³

Results

Of the 224 pts who entered SEQUENCE Part 2, 184 pts had elevated hs-CRP or FCP levels at induction baseline and were included in this analysis. The majority of these pts achieved normalisation of hs-CRP or FCP (per AO data) at wk52 (77.7%) and continued to show improvement at wks 76 and 100 (83.9% and 86.6%, respectively) (Table). Most of these pts also achieved both normalised hs-CRP or FCP and clinical remission simultaneously at wks 52, 76, and 100 per CDAI (AO data: 60.9%, 66.2%, and 71.0%, respectively) and per SF/APS (AO data: 55.2%, 60.2%, and 62.9%, respectively). The proportion of pts who achieved normalisation of hs-CRP or FCP and IBDQ remission increased from wk52 through wk100 (AO data; wk52: 50.0%, wk76: 54.9%, wk100: 57.1%). NRI data for all endpoints are summarized in the Table.

Conclusion

In this post hoc analysis, pts with moderately to severely active CD demonstrated inflammatory biomarker normalisation with RZB treatment and continued improvement of inflammation up to wk100 in the SEQUENCE OLE. Notably, most pts simultaneously achieved normalisation of inflammatory biomarkers plus clinical or QoL outcomes through wk100 of RZB treatment.

References

1. Turner D, et al. Gastroenterology. 2021;160:1570–83.
2. Peyrin-Biroulet L, et al. N Engl J Med. 2024;391:213–23.
3. L Peyrin-Biroulet, et al. Journal of Crohn's and Colitis. 2025;19(Supplement_1):i1405–07.

Disclosure

Benjamin L. Cohen has received advisory board and consultancy fees from AbbVie, ALPCO, Celgene-Bristol Myers Squibb, Johnson & Johnson Innovative Medicine, Lilly, Pfizer, Sublimity Therapeutics, Takeda, TARGET RWE; DSMB: Emmes Biopharma Services LLC; speakers’ fees from AbbVie and Takeda.
Corey Siegel has served as a consultant for AbbVie, BMS, Boomerang, Buhlmann, Celltrion, Johnson & Johnson, Lilly, Napo Pharmaceuticals, Path Healthcare, Pfizer, Prometheus Biosciences & Labs, Sanofi, Takeda, and Trellus Health; received grants from AbbVie, Johson & Johnson, Pfizer, and Takeda; and is co-founder of MiTest Health, LLC, technology “System and Method of Communicating Predicted Medical Outcomes” licensed to Takeda; equity interest in Path Healthcare and Trellus Health
Alessandro Armuzzi has received consulting/advisory board fees from AbbVie, Alfa Sigma, Amgen, Arena, Biogen, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Mylan, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sandoz, Takeda, and Teva Pharmaceuticals; speaker’s fees from AbbVie, Alfa Sigma, Amgen, Arena, Biogen, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, and Teva Pharmaceuticals; and research support from MSD, Takeda, Pfizer, and Biogen.
Fernando Aponte, Toni Anschutz, Andrew Garrison, Namita Joshi, and Javier Zambrano are full-time employees of AbbVie and may own AbbVie stock or stock options.
Laurent Peyrin-Biroulet has received personal fees from AbbVie, Adacyte, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena, Biogen, BMS, Celltrion, CONNECT Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, HAC-Pharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Nordic Pharma, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par’Immune, Pfizer, Prometheus, Protagonist, Roche, Sanofi, Sandoz, Takeda, Theravance, Thermo Fisher, Tigenix, Tillots, Viatris, Vifor, Ysopia, Abivax, Samsung, Ventyx, Roivant, and Vectivbio.

Funding
AbbVie funded this trial and participated in the trial design, research, analysis, data collection, interpretation of data, and the review and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. AbbVie and the authors thank the patients, study sites, and investigators who participated in this clinical trial. Medical writing support was provided by Mahesh Chemudupati, PhD of AbbVie. Editorial support was provided by Amy Kuang, PhD of AbbVie.

Introduction

Despite the benefits of available therapies for Crohn’s disease (CD), many patients (pts) lose treatment response over time, highlighting the need for options with sustained effectiveness.^1-3 Part 2 of the SEQUENCE trial is an open-label extension (OLE) study that evaluates the long-term efficacy and safety of the interleukin-23 p19 inhibitor risankizumab (RZB) in pts with moderate to severe CD and prior anti-TNF failure. Here, we evaluated the durability of clinical remission, quality of life (QoL), and inflammatory biomarker outcomes in RZB-treated pts through week (wk) 100 of SEQUENCE.

Aims & Methods

In SEQUENCE (NCT04524611), pts randomised to the RZB arm during Part 1 who completed the wk48 visit continued to receive open-label 360mg subcutaneous RZB maintenance dose every 8 wks starting at wk52 (baseline of Part 2).⁴ We assessed the proportion of pts achieving clinical remission (per CD activity index [CDAI] and stool frequency/abdominal pain score [SF/APS]) and Inflammatory Bowel Disease Questionnaire (IBDQ) remission at wks 8, 24, 52, 76, and 100. Additionally, pts with elevated high-sensitivity C-reactive protein (hs-CRP; > 5 mg/L) or faecal calprotectin (FCP; > 250 µg/g) at baseline were assessed for normalization of hs-CRP or FCP at wks 8, 24, 52, 76, and 100. We also assessed the proportion of pts who achieved these endpoints at wk100 among pts who also achieved that endpoint previously at either wk8 or at wk52. Data were assessed for all intent-to-treat pts using As Observed (AO) and per Non Responder imputation (NRI). Safety was not assessed in this post hoc analysis, although previously reported.⁵

Results

Of the 224 pts who entered SEQUENCE Part 2, the proportion of pts who achieved clinical remission (per AO data) increased from wk8 to wk52, and remained stable up to wk100 (CDAI: 48.0% [n/N=96/200] at wk8, 75.3% [168/223] at wk52, and 84.4% [141/167] at wk100; SF/APS: 44.0% [88/200] at wk8, 71.2% [158/222] at wk52, and 74.7% [124/166] at wk100) (Table). Similar trends were observed (per AO data) for IBDQ remission (41.5% [88/212] at wk8, 62.1% [139/224] at wk52, and 65.3% [126/193] at wk100), normalisation of hs-CRP (38.8% [54/139] at wk8, 53.1% [76/143] at wk52, and 62.0% [80/129] at wk100), and normalisation of FCP (34.6% [46/133] at wk8, 56.9% [87/153] at wk52, and 60.0% [75/125] at wk100). Most pts who achieved clinical remission at wk8 remained in remission at wk100, and the same was observed for patients in remission at both wk52 and wk100 (AO data; respectively, CDAI: 96.1% [73/76] and 91.1% [123/135]; SF/APS: 90.1% [64/71] and 86.8% [112/129]). A durable effect was also observed from wk8 to wk100 and from wk52 to wk100 in the majority of RZB-treated pts across all other endpoints (AO data; respectively, IBDQ remission: 91.5% [65/71] and 85.7% [102/119]); normalisation of hs-CRP: 80.0% [40/50] and 81.2% [56/69]; normalisation of FCP: 81.1% [30/37] and 85.1% [57/67]). Similar results to AO data were observed per NRI data (Table).

Conclusion

Pts with moderately to severely active CD receiving RZB demonstrated durable clinical remission, IBDQ remission, and inflammatory biomarker reductions through wk100 in the SEQUENCE OLE. Notably, most pts who achieved efficacy endpoints early maintained effectiveness during continued RZB treatment.

References

1. Colombel JF, et al. Gastroenterology. 2007;132:52–65.
2. Hanauer SB, et al. Lancet. 2002;359:1541–9.
3. Turner D, et al. Gastroenterology. 2021;160:1570–83.
4. Peyrin-Biroulet L, et al. N Engl J Med. 2024;391:213–23.

Disclosure

Raja Atreya has served as a speaker, or consultant, or received research grants from AbbVie, Abivax, AlfaSigma, AstraZeneca, Bristol Myers Squibb, CED Service, Celltrion Healthcare, Dr Falk, Galapagos, Johnson & Johnson, Eli Lilly, MSD Sharp & Dohme, Pfizer, Takeda Pharma.
James O. Lindsay has served as a consultant and an advisory board participant for AbbVie, Astra Zeneca, Bristol Myers Squibb, , Celltrion, Eli Lilly, Engytix, Ferring Pharmaceuticals, Galapagos, Gilead, GSK, Janssen, MSD, Pfizer, Takeda, and Vifor Pharma; has received speaker fees and sponsorship for academic meetings from AbbVie, Ferring Pharmaceuticals, Janssen, MSD, Pfizer, Tillotts Pharma, and Takeda; and has received investigator-led research grants from AbbVie, Gilead, Pfizer, and Takeda.
Marc Ferrante has received research grants from AbbVie, EG Pharma, Janssen, Pfizer, Takeda, and Viatris; consultancy fees from AbbVie, AgomAb Therapeutics, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Janssen-Cilag, Merck Sharp and Dohme, MRM Health, Pfizer, Takeda, and ThermoFisher; and speakers’ fees from AbbVie, Biogen, Boehringer Ingelheim, Dr Falk Pharma, Ferring, Janssen-Cilag, Merck Sharp and Dohme, Pfizer, Takeda, Truvion Healthcare, and Viatris.
Britta Siegmund has received consulting fees from AbbVie, Abivax, Boehringer Ingelheim, BMS, Dr Falk, Endpoint Health, Galapagos, Gilead, Janssen, Landos, Lilly, Pfizer, and Takeda, and speaker’s fees from AbbVie, AlfaSigma, BMS, CED Service, Dr Falk, Ferring, Galapagos, Janssen, Lilly, MSD, Pfizer, and Takeda.
Qian Cao has served as a steering committee adviser for Bristol Myers Squibb Company, and Janssen Research Development, LLC; and has received research grants from Takeda and Johnson & Johnson.
Stijn van Haaren, Jameson Crowley, Toni Anschutz, and Andrew Garrison are full-time employees of AbbVie and may own AbbVie stock or stock options.
Marla Dubinsky has received consulting and advisory fees from AbbVie, Abivax, Astra Zeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Eli Lilly, Genentech, Gilead, GSK, Janssen, Johnson and Johnson, Merck, Pfizer, Prometheus Labs, Prometheus Biosciences, Sanofi, Spyre and Takeda
Funding: AbbVie funded this trial and participated in the trial design, research, analysis, data collection, interpretation of data, and the review and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. AbbVie and the authors thank the patients, study sites, and investigators who participated in this clinical trial. Medical writing support was provided by Mahesh Chemudupati, PhD of AbbVie. Editorial support was provided by Amy Kuang, PhD of AbbVie.