Introduction

The Phase 3 QUASAR Maintenance Study is a randomized-withdrawal, double-blind, placebo (PBO)-controlled, study that evaluated the efficacy and safety of maintenance treatment with subcutaneous (SC) guselkumab (GUS), a dual-acting IL-23p19 subunit inhibitor that binds to CD64, in patients (pts) with moderately to severely active ulcerative colitis (UC) who had prior inadequate response or intolerance to conventional or advanced therapy (ADT) and demonstrated a clinical response to GUS IV induction.

Aims & Methods

At maintenance baseline, clinical responders to 12 weeks of GUS IV induction from QUASAR Phase 2b and Phase 3 induction studies (NCT04033445) were randomized 1:1:1 to SC GUS 200mg q4w, GUS 100mg q8w, or PBO (GUS withdrawal). The primary endpoint was clinical remission at Week (Wk) 44. Major secondary endpoints included corticosteroid-free clinical remission, maintenance of clinical remission, maintenance of clinical response, symptomatic remission, endoscopic improvement, histo-endoscopic mucosal improvement, and endoscopic normalization (remission) at Wk44.

Results

The primary analysis population included 568 pts (mean age, 40.7yr; mean UC duration, 7.8yr; mean modified Mayo score, 6.9 [63.9% with severe disease]; Mayo endoscopy subscore of 3, 66.4%; baseline oral corticosteroid use, 40.0%). Approximately 42% had prior inadequate response or intolerance to ADT (TNF antagonists, vedolizumab, or tofacitinib), and 48.3% of these pts failed ≥2 ADT. Disease characteristics were similar across treatment groups at induction and maintenance baseline.
With both GUS SC maintenance regimens, a significantly higher proportion of pts achieved the primary endpoint and all the major secondary endpoints at Wk44 compared with GUS withdrawal (Table 1).
The proportion of pts with ≥1 adverse events (AEs) was similar across treatment groups: GUS 200mg q4w, 70.0%; GUS 100mg q8w, 64.5%, and GUS withdrawal, 68.2%. The most common AEs in the combined GUS group vs withdrawal group were COVID-19 (11.2% vs 14.1%), UC (11.2% vs 29.7%), and arthralgia (6.1% vs 6.8%), respectively.
No cases of death, active tuberculosis, opportunistic infection, anaphylaxis, serum sickness, Hy’s Law, or serious hepatic AEs were reported. Two cases of malignancy (clear cell renal carcinoma, rectal adenocarcinoma) and 1 major adverse cardiovascular event (hemorrhagic stroke) were reported among GUS-treated pts (primary safety population).

Table 1. Primary and major secondary endpoints at Week 44: Primary analysis population

Conclusion

Among pts with moderately to severely active UC who responded to GUS IV induction, maintenance therapy with both GUS SC regimens was safe and efficacious. The primary endpoint of clinical remission and all secondary endpoints across clinical, symptomatic, endoscopic, and histologic measures were met with statistical significance by both GUS SC maintenance regimens. Safety results through maintenance Wk44 were consistent with the known and favorable safety profile of GUS in approved indications.

Disclosure

DTR: AbbVie, Altrubio, Allergan, Inc., Arena Pharmaceuticals, Aslan Pharmaceuticals, Athos Therapeutics, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Ltd., Bristol Myers Squibb, Celgene Corp/Syneos, Connect BioPharma, GalenPharma/Atlantica, Genentech/Roche, InDex Pharmaceuticals, Ironwood Pharmaceuticals, Iterative Scopes, Janssen Pharmaceuticals, Eli Lilly, Materia Prima, Pfizer, Prometheus Biosciences, Reistone, Takeda, Techlab, Inc and is a co-founder of Cornerstones Health, Inc.
JRA: Finch Therapeutics, Artugen, Pfizer, Takeda, Janssen, and Iterative Scopes, Merck and BMS.
JP: AbbVie, Alimentiv, Athos, Atomwise, Boehringer Ingelheim, Celsius, Ferring, Galapagos, Genentech/Roche, GlaxoSmithKline, Janssen, Mirum, Nimbus, Pfizer, Progenity, Prometheus, Protagonist, Revolo, Sanofi, Sorriso, Surrozen, Takeda, and Wasserman.
NS, SY, KGH, MG, RW, and HZ: Employees of Johnson & Johnson.
BGF: AbbVie Inc., Amgen Inc., AdMIRx Inc., Akebia Therapeutics, Allergan, AstraZeneca/MedImmune Ltd., Applied Molecular Transport, Aptevo Therapeutics, Asta Pharma, Atlantic Pharmaceuticals Ltd., Avaxia Biologics Inc., Avir Pharma, Biogen Idec, BioMx Isreal, Boehringer -Ingelheim, Boston Pharmaceuticals, Bristol-Myers Sqibb, Calypso Biotech, Celgene Corporation, Celltech, Centocor Inc, Elan/Biogen, Ferring Pharma, Genentech Inc/Hoffmann-La Roche Ltd., Galapagos, Galen/Atlantica, GiCare Pharma, Gilead Sciences Inc., Gossamer Pharma, GlaxoSmithKline (GSK), Inception IBD Inc, Intact Therapeutics, Janssen Research & Development LLC., Kyowa Kakko Kirin Co Ltd., Lexicon, Lilly, Lycera BioTech, merck, Mesoblast Pharma, Millennium, Nestles, Nextbiotix, Novonordisk, ParImmune, Parvus Therapeutics, Pfizer Inc., Prometheus Therapeutics and Diagnostics, Progenity, Protagonist, Qu Biologics, Rebiotix, Receptos Inc. / Celgene International, Salix Pharma, Sanofi, Santarus Inc., Shire, Sienna Biologics, Sihmoid Pharma, Sterna Biologics, Synergy Pharma Inc., Takeda Development Center Americas Inc., Teva Pharam, TiGenix, Tillotts Pharma AG, UCB, Vertex Pharma, Vivelix Pharma, VHsquared Ltd., Zyngenia and Senior Scientific Officer – Robarts Clinical Trials Inc.
TH: AbbVie, Daiichi-Sankyo, EA Pharma Co, Ltd. Janssen Research & Development LLC., JIMRO, Mitsubishi Tanabe Pharma Corporation, Mochida Pharmacuetical Co., Ltd., Nippon Kayaku Co., Ltd., Pfizer Inc., and Takeda Pharmaceutical Co., Ltd.,
GRL: Abbvie, Allergan, American College of Gastroenterology, American Gastroenterological Association, American Regent, Celgene, Chemed, Eli Lilly, Endo Pharmaceuticals, Ferring, Gastroenterology and Hepatology, Gilead, IMEDEX, Ironwood, Janssen/ Janssen Orthobiotech, MedEd Consultants, Merck, Morphic Therapeutics, Pfizer Pharmaceuticals, Professional Communications, Inc., Prometheus Laboratories, Inc, Romark, Sandoz, Salix Pharmaceuticals/Valeant, Shire Pharmaceuticals, SLACK, Inc, Springer Science and Business Media, Takeda, University of Kentucky, UCB, Up-To-Date, Vindico, and Virgo.
BB: Abbvie, Amgen, BI, BMS, Ferring, Janssen, Merck, Novartis, Organon, Pfizer, Sandoz, Takeda, Alimentiv, Allergan, AMT, Bausch Health, Celgene, Celltrion Healthcare, Eupraxia, Fresenius Kabi, Genentech, GSK, Gilead, Iterative Scopes, Jamp Pharma, Merck Amgen, Microbiome Insights, Mylan, Pendopharm, Protagonist, Qu Biologic, and Viatrisgen.
LPB: AbbVie, Allergan, Alma, Amgen, Applied Molecular Transport, Arena, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, CTMA, Enterome, Enthera, Ferring, Fresenius, Genentech, Gilead, Hikma, Index Pharmaceuticals, Janssen, Lilly, MSD, Mylan, Nestlé, Norgine, Oppilan Pharma, OSE Immunotherapeutics, Pfizer, Pharmacosmos, Roche, Samsung Bioepis, Sandoz, Sterna, Sublimity Therapeutics, Takeda, Tillots and Vifor; grants from AbbVie, MSD and Takeda.
BES: Abbvie, Abbivax, Alimentiv, Amgen, Arena Pharmaceuticals, Artugen Therapeutics, Astra Zeneca, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Calibr, Celgene, Celltrion, ClostraBio, Equillium, Enthera, Evommune, Fresenius Kabi, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Janssen, Kaleido, Kallyope, Lilly, Merck, Morphic Therapeutics, MRM Health, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Sun Pharma, Surrozen, Takeda, Target RWE, Teva, Theravance Biopharma, TLL Pharmaceutical, and Ventyx Biosciences.
AD: Abivax, AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Boehringer Ingelheim, Bristol Myers Squibb/Celgene, CED Service GmbH, Celltrion, Dr Falk Foundation, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos, Gilead, High5MD, Janssen, Lilly, Materia Prima, MedToday, MSD, Pfizer, Pharmacosmos, Roche/Genetech, Sandoz/Hexal, Takeda, Thieme, Tillotts, UniMed Verlag, and Vifor Pharma.

Introduction

Janus kinase (JAK) inhibitors have emerged as an important therapeutic class for the management of several immune-mediated conditions, including inflammatory bowel disease (IBD), but they are associated with several side effects. A renewed attention to the safety profile of this drug class has been driven by increasing reports of JAK inhibitor-induced acneiform eruptions seen in clinical trials and real-life practice.

Aims & Methods

We aimed to investigate the epidemiology, clinical characteristics, and treatment outcomes of this condition in patients with IBD. This was an international, multicenter, retrospective cohort study that consecutively enrolled patients with IBD who were treated with JAK inhibitors and subsequently developed acne. The primary objective was to evaluate the clinical characteristics of acne presentation. Secondary objectives included determining acne prevalence, assessing its impact on quality of life, and evaluating the effectiveness of treatments.

Results

Of the 2,183 JAK inhibitor-treated patients with IBD screened, 272 developed acne and were included in the study. The crude prevalence rates of acne were 15.9% for upadacitinib, 4.3% for tofacitinib, and 1.9% for filgotinib, with dose-dependent relationships observed for upadacitinib and tofacitinib. Acne predominantly affected patients aged 30–50 years, with most cases being mild to moderate in severity. Acneiform eruptions most frequently involved the face (89%), followed by the back (33%) and chest (27%). Lesion characteristics were documented in 159 patients; papules (82%), pustules (52%), and comedones (42%) were the most frequently reported. In contrast, nodules (19%) and cysts (18%) – features associated with more severe disease – were less commonly observed. Among the 213 patients with available time-to-onset data, the median time to acne onset following JAK inhibitor initiation was 47 days (IQR: 28–98 days). Patients with a previous history of acne vulgaris were significantly more likely to develop severe drug-induced acne (p<0.0001). Although corticosteroids are known to contribute to acne, our data did not demonstrate an association between concomitant steroid use and increased acne severity. There was also no difference in time to onset or resolution of acne between the steroid-treated and non-steroid treated groups. A third of patients reported a negative impact on psychosocial well-being, and 40% required pharmacological intervention. Topical therapies were required for 106 patients (39%), with 52 (49%) showing acne improvement or resolution. Systemic oral agents were required for 38 patients (14%), including 25 patients who did not respond or had a partial response to topical therapies. Antibiotics were prescribed to 29 patients (most commonly from the tetracycline class), leading to acne improvement or resolution in 14 patients (48%). Oral isotretinoin was required for 8 patients (3%) and was effective in all but one patient. Eighteen percent of patients who developed acne (2.2% of total cohort) required a JAK inhibitor dose reduction or discontinuation, although most did not have severe disease.

Conclusion

This study is the first to characterise this adverse event in JAK inhibitor-treated patients with IBD and presents the largest cohort of JAK inhibitor-induced acne cases to date across all immune-mediated diseases. JAK inhibitor-induced acne is a common adverse effect resulting in significant psychological burden. Early identification, proactive counselling, and timely interventions, such as dose reduction or referral to dermatology, are crucial in managing this side effect.

Introduction

Interleukin (IL) inhibitors are monoclonal antibodies that have been shown to be effective in inducing and maintaining remission in moderate to severe ulcerative colitis (UC).
Ustekinumab (UST) was approved in the EU for the treatment of UC in 2019 and binds specifically to the p40 protein subunit of IL-12 and IL-23. Mirikizumab (MIRI) was approved 4 years later and selectively binds to the p19 subunit of the IL-23 cytokine. By binding to the IL subunits, the interaction with the IL-23 receptor is inhibited.
In this study, we compared the response rate to induction therapy with UST and MIRI in patients with moderately to severe UC.

Aims & Methods

All patients with active UC who began induction therapy with UST or MIRI at our outpatient clinic between 2019 and 2024 were analyzed retrospectively with a follow-up period until April 2025. Patients who received the IL-23 inhibitor due to a disease other than UC or following a prednisolone therapy exceeding 20 mg and patients with pouchitis were excluded from the study.
We determined the response to IL-23 therapy 8 to 24 weeks after the start of treatment and documented this either as clinical remission (Mayo-Score ≤1), improvement (Mayo-Score reduction by at least 3 points), inadequate response (Mayo-Score reduction between 0 and 2) or no response (lack of benefit, switch to another medical class or colectomy).
We examined the levels of calprotectin in the stool 0 to 24 weeks before the start of IL-23 therapy up to 24 weeks after initial administration.
Our study included 40 patients treated with UST and 23 patients treated with MIRI, in the latter group 26% have previously been treated with UST. Patients in both groups were similar in age (mean age, 47.75 vs. 44.59 y; P 0.28), gender, disease duration (mean duration, 11 vs. 9 y; P 0.32), and extent of disease (pancolitis, 40% vs. 48%).

Results

After completion of induction, 25% in the UST group and 57% in the MIRI group reached clinical remission. MIRI after UST achieved clinical remission in 67%. Improvement was shown in 20% vs. 30%, UST vs. MIRI. For UST, 5% were non-responder. For MIRI, no non-responder was noted. In general, the difference between the pre- and post-induction Mayo-Score is significantly higher for MIRI, indicating a better response to the newly started drug (mean Mayo-Score difference, UST vs. MIRI, 2.95 vs 4.5; P 0.0003)
The mean calprotectin level before treatment was not significantly different (mean calprotectin, UST vs. MIRI, 1652 vs. 2452 mg/kg; P 0.17). The post-treatment calprotectin level was significantly higher for UST vs. MIRI (mean calprotectin, 1092 vs. 278 mg/kg; P 0.0083).

Conclusion

Mirikizumab is an effective induction treatment for patients with active ulcerative colitis, including those who previously did not respond adequately to Ustekinumab therapy.

Introduction

The effectiveness of fecal microbiota transplantation (FMT) in Ulcerative colitis (UC) remains unclear, with significant differences in protocols and procedures among clinical trials (1).

Aims & Methods

This study aimed to investigate the feasibility and effectiveness of a FMT protocol with close infusions in patients with active UC, also exploring the microbial modulation underlying its therapeutic efficacy.

In this prospective cohort study, subjects with mild-to-moderately active UC received three consecutive fecal infusions by colonoscopy, at baseline, T1 (2 weeks) and T2 (6 weeks) respectively. Faeces were collected by the donor on the day of the infusion and processed within 6 hours. A control population with the same baseline features undergoing Infliximab treatment was enrolled. Primary outcomes were the number of adverse events and the compliance rate. Secondary outcomes were: clinical remission; clinical response; endoscopic remission; microbial differences.

Results

Nineteen patients with mild-to-moderately active UC were enrolled.
During the protocol, 2 patients dropped out because of disease worsening and 1 patients dropped out because of hospitalization due to nephrolithiasis.
Clinical response was obtained in 6 of 16 patients at week-2 (PP=37%; ITT=31%), in 8 of 16 at week-6 (PP=50%; ITT=42%), and in 9 at week-12 (PP=56%; ITT=47%). Clinical response was maintained in 8 patients at week 24 (PP=50%; ITT=42%). Clinical remission was achieved in 4 subjects at week-2, in 5 at week-6 (PP=31%; ITT=26%), and in 5 at week-12 (PP=31%; ITT=26%). Endoscopic remission at week 12 was reached in 6 patients (PP=37%; ITT=31%). In the control population, 13 of 19 patients achieved clinical response at week 6 and 10 of 19 patients maintained clinical response after 6 months.
During the time course, the microbiota richness was higher in responders compared with the non-responders. Peptostreptococcus, Lactobacillus and Veillonella were higher in non-responders while Parabacteroides, Bacteroides, Faecalibacterium and Akkermansia were higher in responders in all time points.

Conclusion

Serial FMT infusions appear to be feasible, safe, and able to provide a considerable clinical and microbial response in UC patients. In particular, the comparison with patients under biologic therapy suggests a potential role in maintaining clinical response or enhancing maintenance. Gut microbiota profiling highlighted the role of specific intestinal bacteria in predicting both negative and positive response to FMT.

References

1. Tan XY, Xie YJ, Liu XL, Li XY, Jia B. A Systematic Review and Meta-Analysis of Randomized Controlled Trials of Fecal Microbiota Transplantation for the Treatment of Inflammatory Bowel Disease. Evid Based Complement Alternat Med. 2022;2022:8266793. Published 2022 Jun 26. doi:10.1155/2022/8266793

Introduction

Etrasimod is an investigational, oral, once-daily (QD), selective sphingosine 1‑phosphate (S1P)_1,4,5 receptor modulator in development to treat immune-mediated inflammatory disorders. Etrasimod regulates lymphocyte egress from secondary lymphatic organs and therefore may have promise in the immune cell mediated disease, eosinophilic oesophagitis (EoE).

Aims & Methods

This analysis aimed to investigate the efficacy and safety of oral etrasimod 1 and 2 mg QD vs placebo (PBO) in adults with active EoE. VOYAGE (NCT04682639) was a phase 2 study with a 24-week (wk) randomised, double-blind, PBO‑controlled treatment period, followed by a 28-wk extension period. The primary efficacy endpoint was the percentage change from baseline (BL) (%CFB) in oesophageal peak eosinophil count (PEC) at Wk 16. Other efficacy endpoints assessed the effects of etrasimod on histological and endoscopic features and symptoms of EoE, and included proportion of patients (pts) who achieved PEC <15 and ≤6 eosinophils/high power field, absolute CFB in EoE‑Histology Scoring System (EoE-HSS) grade and stage scores, EoE Endoscopic Reference Score (EREFS), Patient Global Impression of Severity (PGIS) and Dysphagia Symptom Questionnaire (DSQ; overall and by BL dilation history) at Wk 24. We present the findings from the double-blind treatment period.

Results

We randomised 108 pts with active EoE to etrasimod 2 mg QD (N=41), etrasimod 1 mg QD (N=39) or PBO (N=28); 47.2% of pts were female and BL average duration of EoE was 4.6 years, with 55.6% having a history of oesophageal dilation and 40.0% having prior corticosteroid treatment. Treatment with etrasimod 2 mg QD resulted in a 46.1% decrease from BL in PEC (PBO-adjusted) at Wk 16 (p=0.0103) and statistically significant reductions in %CFB in PEC at Wk 24, and reductions in absolute CFB in EoE‑HSS grade and stage scores, EREFS, PGIS and, in pts without BL dilation history, DSQ score (Table). In etrasimod 1 mg- vs PBO‑treated pts, there were statistically significant reductions in %CFB in PEC and absolute CFB in EoE-HSS grade and stage scores at Wk 24. There were no serious treatment‑emergent adverse events (TEAEs) reported up to Wk 24; 2 pts discontinued due to TEAEs (Table).

Conclusion

Etrasimod 2 mg QD met the primary histologic endpoint and significantly improved endoscopic features of EoE, overall symptom severity and dysphagia (in pts without dilation history only) at Wk 24 and was well tolerated. This supports further evaluation of etrasimod in EoE.

Disclosure

ESD has received grant/research support from Adare/Ellodi, Allakos, Arena/Pfizer, AstraZeneca, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos/BMS, Regeneron, Revolo and Shire/Takeda; has received consulting fees from Abbott, AbbVie, Adare/Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/BMS, Celldex, EsoCap, Eupraxia, Ferring, GSK, Gossamer Bio, Holoclara, Invea, Knightpoint, Landos, Lilly, LucidDx, Morphic, Nexstone Immunology, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE and Upstream Bio; and has received educational grants from Allakos, Holoclara and Invea. MHC has been a consultant for Alimentiv/Robarts, Allakos, Arena, BMS, EsoCap, Pfizer, Regeneron, Sanofi, Shire a Takeda company and AstraZeneca. AJB has received grant/research support from Nutricia, Norgine, Dr. Falk Pharma, Thelial, Sanofi/Regeneron and SST; lecture fees from Laborie, Medtronic, Dr. Falk Pharma, Reckitt, Aqilion, Eupraxia, Alimentiv, Sanofi/Regeneron and AstraZeneca; and has received consulting fees from Laborie, Medtronic, Dr. Falk Pharma, Reckitt, Aqilion, Eupraxia, Alimentiv, Sanofi/Regeneron and AstraZeneca. HP has received research grants from Hospital Research Foundation South Australia; is a speaker for Falk and GSK; and has received consulting fees from AusEE and Falk. LB has received consulting fees from AbbVie, Calypso, Esocap, Ewopharma, Falk, Ferring, Janssen, MSD, Pfizer Inc, Sanofi, Shire, Takeda and Vifor. MD, CS, JY, WW and JCW are employees and shareholders of Pfizer Inc. TNC and HZ were employees and shareholders of Pfizer Inc at the time the work was completed. FC was an employee of Arena Pharmaceuticals, San Diego, CA, USA; a wholly-owned subsidiary of Pfizer Inc, New York, NY, USA at the time of analysis. IH has received research/grants from NIH, Adare/Ellodi, Allakos, Arena, AstraZeneca, Meritage, Celgene/Receptos/BMS, Regeneron and Shire/Takeda; and consulting fees from Adare/Ellodi, Allakos, Amgen, Arena/Pfizer, Aslan, AstraZeneca, Celgene/Receptos/BMS, Celldex, EsoCap, Gossamer Bio, Nexstone Immunology, Parexel/Calyx, Phathom, Regeneron, Sanofi and Shire/Takeda.

Introduction

The primary objective of the VERDICT study, a continuing randomized controlled trial (NCT04259138),^1,2 is to determine the optimal treatment target in moderately‑to-severely active ulcerative colitis (UC). Patients are allocated to Group 1 (corticosteroid-free [CSF] symptomatic remission), Group 2 (CSF symptomatic remission + CSF endoscopic remission), and Group 3 (CSF symptomatic remission + CSF endoscopic remission + CSF histologic remission, also termed disease clearance). Patients follow treatment algorithms involving early introduction of vedolizumab (VDZ), without week 10 dosing, nor dose escalation before week 16. Here we report target achievement at weeks 16 and 32 amongst groups.

Aims & Methods

VDZ 300 mg was administered intravenously following a treatment algorithm related to baseline UC treatment until assigned treatment target was reached at week 32, with an escalation step between week 16 and 32 as indicated. CSF symptomatic remission was defined as Mayo rectal bleeding subscore=0, CSF endoscopic remission was defined as Mayo Endoscopic Score [MES]≤1, and CSF histologic remission was defined as Geboes score<2B.0.

Results

As of 29 Feb 2024, 612 patients were enrolled with 154, 198, and 260 patients assigned to target Groups 1, 2, and 3, respectively. Baseline age and disease duration were similar amongst groups, with respective percentages of patients having baseline MES=3 given by 60.4%, 61.6%, and 64.2%, and receipt of concomitant corticosteroids given by 42.9%, 40.9%, and 50.4% (median dose 25.4, 25.3, and 23.7 mg). There were 71.4%, 75.3%, and 83.5% of patients who were bionaïve, respectively. At time of analysis, 63.6%, 71.2%, and 80.8% of randomized patients in the groups had completed the week 32 visit.
In patients with observed data and a week 16 visit, 64.1% (75/117), 42.2% (73/173), and 40.2% (94/234) in Groups 1, 2, and 3, respectively, achieved CSF remission at week 16. In patients with observed data and a week 32 visit, 81.6% (80/98), 61.7% (87/141), and 53.3% (112/210), respectively, achieved CSF remission by week 32, with higher proportions in bionaïve (83.7%, 63.8%, and 55.2%) compared to bio-exposed (66.7%, 52.0%, and 40.7%) (Table 1). In the intention-to-treat population, 48.7%, 36.9%, and 36.2% of patients, respectively, achieved CSF remission at week 16, with higher proportions in patients who were bionaïve (56.4% [62/110], 38.3% [57/149], and 38.2% [83/217]) compared to bio-exposed (29.5% [13/44], 32.7% [16/49], and 25.6% [11/43]). By week 32, 51.9%, 43.9%, and 43.1% of the intention-to-treat population achieved CSF remission, with higher proportions in bionaïve (65.5% [72/110], 49.7% [74/149], and 46.5% [101/217]) compared to bio-exposed (18.2% [8/44], 26.5% [13/49], and 25.6% [11/43]). For patients not achieving target at week 16, treatment escalation occurred in 22.7%, 49.5%, and 53.5% of patients; after escalation, proportions achieving CSF remission by week 32 were 41.9% (13/31), 27.0% (20/74), and 19.0% (23/121), respectively.

Conclusion

These interim week 32 results provide evidence of improvement from week 16 to 32 across all endpoints and continue to support the efficacy of VDZ in achieving the stringent endpoint of CSF disease clearance.

References

¹Jairath V, Zou G, Wang Z, et al. Determining the optimal treatment target in patients with ulcerative colitis: rationale, design, protocol and interim analysis for the randomised controlled VERDICT trial. BMJ Open Gastroenterol. 2024;11:e001218. Doi:10.1136/bmjgast-2023-001218
²Jairath V, Zou G, Adsul S, et al. DOP11 Disease clearance after 16 weeks of treatment with vedolizumab in patients with moderate to severe Ulcerative Colitis: An interim analysis from the VERDICT trial. J Crohns Colitis. 2024;18 (Suppl 1):i92-i93. Doi: 10.1093/ecco-jcc/jjad212.0051

Disclosure

VJ has received consulting/advisory board fees from Alimentiv Inc. (formerly Robarts Clinical Trials) and Takeda; and received speaker’s fees from Takeda.
GZ has received consulting fees from Alimentiv Inc.
SA and MF are employees of Takeda Pharmaceuticals.
LPB has received personal fees from Alimentiv Inc. and Takeda.
JFC reports receiving research grants, payment for lectures, and consulting fees from Takeda.
GRD has served as a consultant and/or received speaker fees from Alimentiv Inc. and Takeda.
GWM is a consultant for Alimentiv Inc.
WJS reports receiving consulting fees from Alimentiv Inc.
SS reports receiving research grants from Takeda; and receiving personal fees for speaker role and advisory board meetings from Takeda outside the submitted work.
ST has received grants/research support, consulting fees, and speaker fees from Takeda,
SV has received grants from Takeda; and received consulting and/or speaking fees from Alimentiv Inc. and Takeda.
JH has received consulting fees from Alimentiv Inc. and speaker’s fees from Takeda.
CM has received consulting fees from Alimentiv Inc. and has received consulting fees and speaker's fees from Takeda.
RS has received consulting fees from Alimentiv Inc.
PS is an employee of Alimentiv Inc.
NA reports no conflicts of interest.
MB has received honoraria and advisory board fees from Takeda; and reports clinical trials with Takeda.
PB reports receiving research grants, lecture fees, and consulting fees from Takeda.
SD reports consultancy fees from Alimentiv Inc. and reports consultancy fees and lecture fees from Takeda.
DG has received advisory board fees from Takeda.
WH reports no conflicts of interest.
MH reports no conflicts of interest.
JK reports no conflicts of interest with Alimentiv Inc. or Takeda
AK reports no conflicts of interest.
MK has received personal fees from Shire, a Takeda company, during the conduct of the study, and received personal fees and non-financial support from Takeda.
FM has received fees from Takeda.
RP reports no conflicts of interest with Alimentiv Inc. and Takeda.
MSS has received consulting, speaker, and advisory board fees from Takeda.
LW reports no conflicts of interest.
BGF is a scientific advisory board member for Takeda; has received consulting fees, lecture fees, and grant support from Takeda; and is the Senior Scientific Officer of Alimentiv Inc.