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Inflammatory Bowell

Phase 2b/3 QUASAR Program: Guselkumab for Induction and Maintenance Therapy in Moderate-to-Severe Ulcerative Colitis

7 Jan, 2025 | 13:00h | UTC

Background: Ulcerative colitis (UC) is a chronic inflammatory condition affecting the colon’s mucosal surface, frequently accompanied by debilitating symptoms such as bloody diarrhea, urgency, and abdominal discomfort. Despite the availability of corticosteroids, immunosuppressants, and advanced biologic or small-molecule therapies, many patients still experience suboptimal outcomes. Targeting interleukin (IL)-23, a critical cytokine in the inflammatory cascade, has gained increasing attention. Guselkumab, a human IgG1 monoclonal antibody against the IL-23p19 subunit, has shown clinical promise in psoriasis, psoriatic arthritis, and Crohn’s disease. This article reports findings from the phase 2b/3 QUASAR clinical development program evaluating guselkumab in UC.

Objective: To assess the efficacy and safety of intravenous (IV) guselkumab induction therapy (200 mg every 4 weeks) compared to placebo, followed by subcutaneous (SC) maintenance regimens (200 mg every 4 weeks or 100 mg every 8 weeks) compared to placebo (withdrawal) in adults with moderately to severely active UC who had inadequate responses or intolerance to at least one conventional or advanced therapy.

Methods: In these double-blind, randomized, placebo-controlled studies within the QUASAR program, adults with a baseline modified Mayo (mMayo) score of 5–9 (which excludes the physician’s global assessment) and evidence of active UC underwent IV induction with either guselkumab or placebo at Weeks 0, 4, and 8. The primary endpoint of the induction trial was clinical remission at Week 12 in the primary analysis population (patients with mMayo score 5-9), defined by improved stool frequency, rectal bleeding, and endoscopic findings. Responders from both the phase 2b and phase 3 induction studies then entered the maintenance study, randomized to SC guselkumab (either 200 mg Q4W or 100 mg Q8W) or placebo (withdrawal, meaning patients who had previously responded to guselkumab). The primary endpoint for the maintenance phase was clinical remission at Week 44 in the primary analysis population. Key secondary outcomes included endoscopic improvement, histological remission, corticosteroid-free remission, and patient-reported measures.

Results: A total of 701 patients with a baseline mMayo score of 5-9 (primary analysis population) were evaluated in the phase 3 induction study. By Week 12, a higher proportion of those receiving IV guselkumab (23%) achieved clinical remission compared to placebo (8%; p<0.0001). Patients also demonstrated improvement in endoscopic outcomes and had early symptomatic relief (notably a reduction in rectal bleeding as early as Week 1). In the subsequent maintenance phase, 568 guselkumab induction responders from both phase 2b and phase 3 studies (primary analysis population) were randomized. At Week 44, clinical remission was significantly more frequent in patients receiving guselkumab SC (50% on 200 mg Q4W, 45% on 100 mg Q8W) vs 19% on placebo (both p<0.0001). Endoscopic and histological indices indicated improved mucosal healing with active therapy. Most patients in remission were free of corticosteroids, highlighting a significant steroid-sparing effect.

Conclusions: Guselkumab induction (200 mg IV every 4 weeks) followed by either of the two SC maintenance regimens (200 mg Q4W or 100 mg Q8W) demonstrated substantial efficacy in adults with moderate-to-severe UC, with improved clinical, endoscopic, and histological endpoints relative to placebo. No new safety concerns were observed compared to the known safety profile of guselkumab.

Implications for Practice: Guselkumab offers a new therapeutic option for UC, particularly for individuals who have not responded to, or could not tolerate, other treatments. The study suggests that guselkumab can be considered for both biologic-naive and biologic-experienced patients. As with any novel therapy, careful patient selection and close follow-up are advisable.

Study Strengths and Limitations: Strengths include the rigorous, global, phase 2b/3 design with objective assessments of clinical, endoscopic, and histological response. The large population permitted detailed subgroup analyses (e.g., efficacy was observed in both biologic-naive and biologic-experienced populations). Limitations include the exclusion of certain therapy-refractory cases and lack of active comparator arms. The randomized-withdrawal maintenance design means only induction responders were evaluated further, potentially enhancing observed effect sizes.

Future Research: Extended follow-up will elucidate the durability of remission beyond one year and clarify long-term safety considerations. Head-to-head trials against other IL-23 antagonists or advanced therapies could further guide treatment algorithms. Real-world evidence evaluating diverse populations will be instrumental in determining broader applicability.

Reference: Rubin DT, Allegretti JR, Panés J, Shipitofsky N, Yarandi SS, Huang K-HG, Germinaro M, Wilson R, Zhang H, Johanns J, Feagan BG, Hisamatsu T, Lichtenstein GR, Bressler B, Peyrin-Biroulet L, Sands BE, Dignass A; QUASAR Study Group. Guselkumab in patients with moderately to severely active ulcerative colitis (QUASAR): phase 3 double-blind, randomised, placebo-controlled induction and maintenance studies. The Lancet. 2025;405(10472):33–49. DOI: http://doi.org/10.1016/S0140-6736(24)01927-5

Meta-analysis: One-day Low-residue Diet Achieves Comparable Bowel Cleansing Compared to Multi-day Regimens

26 Dec, 2024 | 18:21h | UTC

Background: Colorectal cancer remains a leading cause of cancer-related morbidity worldwide, making early detection through colonoscopy essential. Adequate bowel preparation is crucial to maximize mucosal visibility and detect lesions effectively. Although low-residue diets (LRDs) are commonly recommended before colonoscopy, guidelines vary regarding the optimal duration (one day versus multiple days). This systematic review and meta-analysis evaluated whether a one-day LRD regimen is non-inferior to multi-day protocols in achieving satisfactory bowel cleansing and lesion detection.

Objective: To compare the efficacy of 1-day versus >1-day LRD regimens for bowel preparation in adult patients undergoing elective colonoscopy, focusing on bowel cleanliness, polyp detection, and adenoma detection rates.

Methods: A comprehensive search of PubMed, Cochrane Central Register of Controlled Trials, ScienceDirect, Scopus, and ClinicalTrials.gov was conducted for randomized controlled trials (RCTs) comparing 1-day with >1-day LRD regimens. Six RCTs involving 2,469 participants met inclusion criteria. Patients were randomized to either a 1-day LRD (n=1,237) or a multi-day LRD (n=1,232). Adequate bowel preparation was primarily defined by a Boston Bowel Preparation Scale (BBPS) score ≥2 in each segment or total BBPS ≥6. Secondary outcomes included polyp detection rate (PDR), adenoma detection rate (ADR), withdrawal time, cecal intubation rate, and cecal intubation time.

Results: Both groups demonstrated similar rates of adequate bowel preparation (87.2% in the 1-day LRD vs. 87.1% in the multi-day group), with no significant difference (OR=1.03, 95% CI, 0.76–1.41; p=0.84; I2=0%). PDR was likewise comparable (OR=0.91, 95% CI, 0.76–1.09; p=0.29; I2=16%), as was ADR (OR=0.87, 95% CI, 0.71–1.08; p=0.21; I2=0%). Withdrawal time did not differ (MD=–0.01 minutes, 95% CI, –0.25 to 0.24; p=0.97; I2=63%), and cecal intubation parameters were also statistically similar. Across studies, the pooled mean global BBPS revealed minimal difference (MD=0.16, 95% CI, –0.02 to 0.34; p=0.08; I2=15%), confirming the non-inferiority of a shorter LRD protocol.

Conclusions: A one-day LRD achieves bowel cleansing outcomes comparable to those of multi-day LRDs, without compromising polyp or adenoma detection. This shorter regimen may help optimize patient adherence, reduce dietary restriction burden, and simplify procedural logistics, especially for busy endoscopy practices.

Implications for Practice: Adopting a 1-day LRD can streamline preparation, improve patient satisfaction, and maintain high-quality visualization. Clinicians should weigh individual patient factors such as chronic constipation or comorbidities but may generally favor a shorter dietary restriction period to enhance compliance and comfort.

Study Strengths and Limitations: This meta-analysis included only RCTs, strengthening its internal validity. Heterogeneity for primary outcomes was minimal. However, the included trials employed varied dietary protocols and bowel preparation solutions. Additionally, some studies lacked uniform reporting of cecal intubation endpoints, limiting direct comparisons. Future investigations with standardized outcome measures could offer more definitive guidance.

Future Research: Further large-scale RCTs should assess cost-effectiveness, patient-reported outcomes, and LRD composition in specific populations. Identifying optimal dietary instructions for individuals with slower colonic transit or specific nutritional needs would refine colonoscopy preparation guidelines and potentially increase detection of precancerous lesions.

Reference: Putri RD, et al. One-day low-residue diet is equally effective as the multiple-day low-residue diet in achieving adequate bowel cleansing: a meta-analysis of randomized controlled trials. Clinical Endoscopy. 2024. DOI: https://doi.org/10.5946/ce.2024.061

 

Review | Pediatric-onset inflammatory bowel disease: recent developments

27 Jul, 2023 | 12:57h | UTC

Inflammatory bowel disease: recent developments – Archives of Disease in Childhood

 

Systematic Review | Vedolizumab for induction and maintenance of remission in Crohn’s disease

20 Jul, 2023 | 10:51h | UTC

Vedolizumab for induction and maintenance of remission in Crohn’s disease – Cochrane Library

 

RCT | Mirikizumab outperforms placebo in inducing and maintaining remission in ulcerative colitis

10 Jul, 2023 | 13:25h | UTC

Mirikizumab as Induction and Maintenance Therapy for Ulcerative Colitis – New England Journal of Medicine (link to abstract – $ for full-text)

Commentary: Mirikizumab Bests Placebo in Treating Patients With Ulcerative Colitis – HCP Live

 

Commentary on Twitter

 

Consensus Paper | Gut microbiota and fecal microbiota transplantation in inflammatory bowel disease

26 Jun, 2023 | 00:26h | UTC

The first international Rome consensus conference on gut microbiota and faecal microbiota transplantation in inflammatory bowel disease – Gut

 

RCT | JAK inhibitor Upadacitinib shows superiority over placebo for moderate-to-severe Crohn’s disease

1 Jun, 2023 | 12:08h | UTC

Upadacitinib Induction and Maintenance Therapy for Crohn’s Disease – New England Journal of Medicine (link to abstract – $ for full-text)

 

Review | Identifying, understanding and managing fecal urgency in inflammatory bowel diseases

4 May, 2023 | 13:38h | UTC

Identifying, understanding and managing fecal urgency in inflammatory bowel diseases – Clinical Gastroenterology and Hepatology

 

SR | Fecal transplantation for treatment of inflammatory bowel disease

2 May, 2023 | 13:39h | UTC

Fecal transplantation for treatment of inflammatory bowel disease – Cochrane Library

Commentary: Expert reaction to two Cochrane reviews looking at stool transplants for recurrent Clostridium difficile infection, and for inflammatory bowel disease – Science Media Centre

 

RCT | Anti-TNF in combination with low dose methotrexate vs anti-TNF monotherapy in pediatric Crohn’s disease

26 Apr, 2023 | 13:55h | UTC

Comparative Effectiveness of Anti-TNF in Combination with Low Dose Methotrexate vs Anti-TNF Monotherapy in Pediatric Crohn’s Disease: a Pragmatic Randomized Trial – Gastroenterology (link to abstract – $ for full-text)

News Release: Researchers Announce Findings from Landmark Clinical Trial for Pediatric Crohn’s Disease – University of North Carolina Health Care System

 

Brief Review | Chronic cough and inflammatory bowel disease: an under-recognized association?

18 Apr, 2023 | 13:07h | UTC

Chronic cough and inflammatory bowel disease: an under-recognised association? – Breathe

 

Commentary on Twitter

 

RCT | Etrasimod outperforms placebo in ulcerative colitis induction & maintenance

6 Apr, 2023 | 12:56h | UTC

Etrasimod as induction and maintenance therapy for ulcerative colitis (ELEVATE): two randomised, double-blind, placebo-controlled, phase 3 studies – The Lancet

 

Commentary on Twitter

 

Global, regional and national burden of inflammatory bowel disease in 204 countries and territories from 1990 to 2019

5 Apr, 2023 | 13:27h | UTC

Global, regional and national burden of inflammatory bowel disease in 204 countries and territories from 1990 to 2019: a systematic analysis based on the Global Burden of Disease Study 2019 – BMJ Open

 

RCT | Vedolizumab for the treatment of chronic pouchitis

3 Apr, 2023 | 13:49h | UTC

Vedolizumab for the Treatment of Chronic Pouchitis – New England Journal of Medicine (link to abstract – $ for full-text)

News Release: New hope for patients after vedolizumab found effective to treat Chronic Pouchitis – University of Oxford

 

Commentary on Twitter

 

M-A | Has the therapeutical ceiling been reached in Crohn’s disease randomized controlled trials?

17 Mar, 2023 | 12:55h | UTC

Has the therapeutical ceiling been reached in Crohn’s disease randomized controlled trials? A systematic review and meta-analysis – UEG Journal

 

RCT | Induction therapy with olamkicept vs. placebo in patients with active ulcerative colitis

13 Mar, 2023 | 14:48h | UTC

Effect of Induction Therapy With Olamkicept vs Placebo on Clinical Response in Patients With Active Ulcerative Colitis: A Randomized Clinical Trial – JAMA (free for a limited period)

 

Commentary on Twitter

 

Cohort Study | Endoscopic biopsy with normal mucosa associated with elevated risk of inflammatory bowel disease for at least 30 years

8 Mar, 2023 | 14:10h | UTC

Summary:

This study explored the long-term risk of inflammatory bowel disease (IBD) after an endoscopic biopsy with normal mucosa. The researchers identified individuals in Sweden with a lower or upper gastrointestinal (GI) biopsy of normal mucosa, their matched population references, and unexposed full siblings.

They found that individuals with a previous lower or upper GI biopsy showing normal mucosa were at persistently higher risk of overall IBD, ulcerative colitis, and Crohn’s disease compared to their matched population references and unexposed full siblings, and the increased risk persisted at least 30 years after the biopsy with normal findings.

The findings suggest a substantial symptomatic period before IBD diagnosis, and clinicians should be aware of the long-term increased risk of IBD in those with symptoms requiring GI investigation but with a finding of histologically normal mucosa.

Article: Long-term risk of inflammatory bowel disease after endoscopic biopsy with normal mucosa: A population-based, sibling-controlled cohort study in Sweden – PLOS Medicine

Commentary: Risk for IBD Remains High After Endoscopic Biopsy With Normal Mucosa – HealthDay

 

AGA Guideline | Role of biomarkers for the management of ulcerative colitis

22 Feb, 2023 | 12:38h | UTC

AGA Clinical Practice Guideline on the Role of Biomarkers for the Management of Ulcerative Colitis – Gastroenterology

News Release: New AGA guideline recommends blood and stool tests for monitoring ulcerative colitis – American Gastroenterological Association

 

Review | Perioperative optimization of Crohn’s disease

17 Feb, 2023 | 12:39h | UTC

Perioperative optimization of Crohn’s disease – Annals of Gastroenterological Surgery

 

Cohort Study | Antibiotics, hormonal therapies, oral contraceptives, and NSAIDS linked to increased risk of inflammatory bowel disease

16 Feb, 2023 | 14:59h | UTC

Associations of Antibiotics, Hormonal Therapies, Oral Contraceptives, and Long-Term NSAIDS With Inflammatory Bowel Disease: Results From the Prospective Urban Rural Epidemiology (PURE) Study – Clinical Gastroenterology and Hepatology (link to abstract – $ for full-text)

Commentary: Antibiotics, hormonal medications, oral contraceptives, and long-term NSAID tied with IBD – Medical Dialogues

 

Brief Review | Surgical management of ulcerative colitis

13 Feb, 2023 | 12:30h | UTC

Surgical management of ulcerative colitis – British Journal of Surgery

 

ESPEN guideline on clinical nutrition in inflammatory bowel disease

7 Feb, 2023 | 14:02h | UTC

ESPEN guideline on Clinical Nutrition in inflammatory bowel disease – Clinical Nutrition

 

RCT | Withdrawal of infliximab or concomitant immunosuppressant therapy in patients with Crohn’s disease on combination therapy

17 Jan, 2023 | 13:10h | UTC

Withdrawal of infliximab or concomitant immunosuppressant therapy in patients with Crohn’s disease on combination therapy (SPARE): a multicentre, open-label, randomised controlled trial – The Lancet Gastroenterology & Hepatology

Invited commentary: Treatment withdrawal in Crohn’s disease: slowly becoming clearer – The Lancet Gastroenterology & Hepatology (free registration required)

 

Commentary on Twitter

 

Cohort Study | Antibiotic exposure linked to increased risk of inflammatory bowel disease

13 Jan, 2023 | 13:25h | UTC

Antibiotic use as a risk factor for inflammatory bowel disease across the ages: a population-based cohort study – Gut

News Release: Frequent use of antibiotics may heighten inflammatory bowel disease risk in over 40s – BMJ Newsroom

Commentaries: 

Antibiotics may increase risk of inflammatory bowel disease, study finds – CIDRAP

Antibiotic Exposure Positively Linked to IBD Development – HealthDay

 

Commentary on Twitter

 

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