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Introduction

The need for effective therapies in moderate to severe Crohn's disease (CD) drives the comparative evaluation of biologic treatments. The current work uses an anchored Matching-Adjusted Indirect Comparison (MAIC) to assess the efficacy of guselkumab (GUS) relative to risankizumab (RZB) during the treatment induction phase. This MAIC is using data from five phase 3 placebo-controlled blinded clinical trials (GRAVITI, GALAXI 2, GALAXI 3, ADVANCE, MOTIVATE).

Aims & Methods

Adult patients with moderate to severe CD, as defined in GRAVITI, GALAXI 2/3, ADVANCE and MOTIVATE trials were included. An anchored MAIC was utilized, leveraging placebo as common comparator and following guidance from the National Institute for Health Care Excellence in UK. The analysis aligned pooled individual patient data for GUS with published data for RZB by matching exclusion criteria and patient baseline characteristics that could be treatment effect modifiers (eg Age, Sex, BMI, CDAI, disease location or prior biologic treatment failure). During induction, patients received GUS 200 mg intravenous or 400 mg subcutaneous at weeks 0, 4, and 8 or RZB 600 mg intravenous at weeks 0, 4, and 8. The endpoints of interest were symptomatic endpoints such as clinical remission, PRO-2 remission, clinical response, abdominal pain and stool frequency remission, as well as endoscopic response at week 12, which marks the end of the induction period.

Results

After matching, baseline characteristics were balanced between the GUS and RZB cohorts. In a mixed population of bio-naïve and bio-experienced patients, GUS demonstrated statistically significant results in comparison to RZB for PRO-2 remission, clinical response and abdominal pain remission (table 1). Clinical remission showed a trend in favor of GUS, endoscopic response and stool frequence remission were comparable to RZB. In patients with biologic treatment failure versus the MOTIVATE trial, results had been generally more in favor of GUS, while maintaining positive outcomes seen across mixed populations (ADVANCE & MOTIVATE). Results were also mostly consistent whether analyzing pooled GUS data or individual trials, eg from GRAVITI, against RZB.

Table 1: Results of GUS from pooled GRAVITI, GALAXI 2/3 vs. RZB for induction period at week 12

Endpoint	RE measure	Mixed population (ADVANCE & MOTIVATE)		Bio-failure population (MOTIVATE)
		BC	SA	BC	SA
Clinical response	OR [95%CI]	1.78* [1.06; 2.99]	1.42 [0.76; 2.64]	1.71 [0.82; 3.57]	1.23 [0.49; 3.04]
Endoscopic response	OR [95%CI]	1.05 [0.56; 1.97]	1.05 [0.53; 2.09]	1.57 [0.59; 4.18]	1.56 [0.49; 5.01]
Clinical remission	OR [95%CI]	1.51 [0.84; 2.70]	1.22 [0.60; 2.46]	1.52 [0.65; 3.51]	1.08 [0.39; 3.01]
PRO-2 remission	OR [95%CI]	1.96* [1.13; 3.38]	1.85* [1.03; 3.33]	2.89* [1.29; 6.49]	2.97* [1.11; 7.94]
AP score remission	OR [95%CI]	1.68 [1.00; 2.82]	1.37 [0.75; 2.52]	2.02 [0.97; 4.20]	1.68 [0.69; 4.09]
SF score remission	OR [95%CI]	0.99 [0.62; 1.59]	0.93 [0.55; 1.58]	1.14 [0.59; 2.19]	1.04 [0.48; 2.26]

Footnotes: clinical response= ≥100-point reduction from baseline in CDAI OR CDAI <150; endoscopic response= ≥50% improvement from baseline in SES-CD OR SES-CD ≤2; clinical remission= CDAI <150; PRO-2 remission=AP mean daily score at or below 1 [AP≤1] AND SF mean daily score at or below 3 [SF≤3], and no worsening of AP or SF from baseline; AP score remission=Abdominal Pain mean daily score at or below 1 [AP≤1];
SF score remission= number of liquid or very soft stools mean daily score at or below 3 [SF≤3];
BC=baseline risk-adjusted; SA=sensitivity analysis; *p<0,05

Conclusion

The anchored MAIC analysis demonstrates comparable to even superior efficacy of guselkumab over risankizumab in inducing symptomatic improvements in Crohn's disease patients. It also suggests that subcutaneous induction seems to be preferential over iv induction.

Disclosure

van Sanden S, Trevisan M, Strobl A and Wirth D are employees of J&J Innovative Medicines

COMPARATIVE EFFICACY OF GUSELKUMAB VS. RISANKIZUMAB IN INDUCTION PHASE FOR MODERATE TO SEVERE CROHN'S DISEASE: AN ANCHORED MAIC ANALYSIS

Suzy van Sanden 1, Marco Trevisan 2, Alina Strobl 3, Daniel Wirth 3

1 J&J Innovative Medicine, Beerse, Belgium

2 J&J Innovative Medicine, Zug, Switzerland

3 J&J Innovative Medicine, Neuss, Germany

Conference

UEG Week Berlin 2025

Topics

IBD

Submission format

Abstract

Session

IBD (Posters)

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

UEG Podcast Episode

Journal Podcast

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Episode 5: UEG Journal September Spotlight

Mohsan Subhani, Djuna L. Cahen

Published

2025

UEG Podcast Episode

UEG Podcast

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The future of immunotherapy → are surgeons obsolete soon? with Jeroen Dekervel

Jeroen Dekervel, Pradeep Mundre

Topics

Digestive Oncology

Published

2026

UEG Podcast Episode

UEG Podcast

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Best of UEG Week - IBD with Bel Kok

Bel Klaartje Kok, Pradeep Mundre

Topics

IBD

Published

2025

UEG Presentation

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PEGOZAFERMIN DEMONSTRATED ROBUST HISTOLOGICAL IMPROVEMENT AND BENEFIT IN HEPATIC AND METABOLIC BIOMARKERS: RESULTS FROM A 48-WEEK MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 2B TRIAL (ENLIVEN)

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Introduction

Metabolic dysfunction-associated steatohepatitis (MASH) is often associated with metabolic disorders such as obesity, metabolic syndrome, and/or diabetes. FGF21 analogs are promising therapies for MASH due to their direct anti-fibrotic effects as well as additional hepatic and extrahepatic benefits. Pegozafermin (PGZ), an FGF21 analog, was evaluated for safety and efficacy in a Phase 2b trial (ENLIVEN) with either weekly (QW) or every two-week (Q2W) dosing versus matching placebo in MASH patients with biopsy-proven F2/F3 fibrosis. Primary histology endpoints and non-invasive tests (NITs) were assessed at week 24, followed by additional NIT evaluation at the end of a 24-week blinded extension for a total of 48 weeks.

Aims & Methods

Patients were randomized to PGZ 15mg QW, 30mg QW, or 44mg Q2W or placebo for 24 weeks (histology-based primary endpoints). During the 24-week extension, most patients continued their assigned treatment with the exception of a subset of placebo patients who were re-randomized to receive PGZ 30mg QW. The full analysis set includes F2/F3 patients with NAFLD activity score (NAS) ≥4 at baseline (n=192).

Results

At 24-weeks, PGZ 30mg QW or 44mg Q2W led to statistically significant and clinical meaningful improvement in both primary histological endpoints (one stage of fibrosis improvement without worsening of MASH and MASH resolution without worsening of fibrosis) compared to placebo. Non-invasive testing at weeks 24 and 48 demonstrated that PGZ treatment was associated with robust and sustained reductions in liver fat content (MRI-PDFF), biomarkers of fibrosis (VCTE, ELF, PRO-C3) and liver injury (ALT, AST). PGZ also improved metabolic parameters such as lipids and HbA1c at both 24 and 48 weeks. PGZ was generally safe and well tolerated with the most common treatment emergent adverse events (TEAEs) being mild/moderate nausea and diarrhea. No deaths occurred; six early terminations for TEAEs including one drug-related serious AE occurred.

Conclusion

At 24 weeks, treatment with PGZ in MASH patients with F2/F3 fibrosis led to significant fibrosis regression and MASH resolution, which was corroborated by improvement across a variety of non-invasive tests including liver fat, inflammation, fibrosis, and metabolic markers. Benefits on NITs were sustained over the full 48-weeks of the study, with favorable safety and tolerability. PGZ is the first therapy to achieve fibrosis regression and MASH resolution with a Q2W dosing regimen. Phase 3 studies in noncirrhotic (ENLIGHTEN-Fibrosis) and cirrhotic (ENLIGHTEN-cirrhosis) patients are currently underway to confirm these results.

Disclosure

Jörn Schattenberg: Consultant: Akero, Alentis Therapeutics, Astra Zeneca, 89Bio, Boehringer Ingelheim, GSK, Ipsen, Inventiva Pharma, Madrigal, MSD, Northsea Therapeutics, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi, Siemens Healthineers; Speaker: Gilead Sciences, Advanz, Echosens, MedPublico GmbH; Grants: Boehringer Ingelheim, Siemens Healthcare GmbH; Stock Options: AGED diagnostics, Hepta Bio
Arun J Sanyal: Consulting: Genefit, Gilead, Malinckrodt, Pfizer, Salix, Boehringer Ingelheim, Novartis, Bristol Meyers Squibb, Merck, Hemoshear, Lilly, Novo Nordisk, Terns, Albireo, Jannsen, Poxel, 89bio, Siemens, AstraZeneca, NGM Bio, Amgen, Regeneron, Genentech, Alnylam, Roche, Madrigal, Inventiva, Covance, Prosciento, HistoIndex, PathAI; Grants: Gilead, Malinckrodt, Boehringer Ingelheim, Novartis, Bristol Meyers Squibb, Merck, Lilly, Novo Nordisk, Fractyl, Madrigal, Inventiva; Stock holder: Exhalenz, GenFit, Hemoshear, Durect, Indalo, NorthSea, Tiziana, Rivus
Naim Alkhouri: Research funding: 89Bio, AbbVie/Allergan, Akero, Better Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Corcept, DSM, Galectin, Genentech, Genfit, Gilead, Hepagene, Healio, Intercept, Inventiva, Ionis, Madrigal, Merck, NGM, Noom, NorthSea, Novo Nordisk, Perspectum, Pfizer, Poxel, Viking, and Zydus; Speaker bureau: AbbVie/Allergan, Alexion, Echosens, Eisai, Exelixis, Gilead, Intercept, Perspectum, Salix, and Theratechnologies; Consultant: 89Bio, AbbVie/Allergan, Echosens, Fibronostics, Gilead, Intercept, Madrigal, Novo Nordisk, Perspectum, Pfizer, and Zydus.
Rohit Loomba: Consultant: Aardvark Therapeutics, Altimmune, Anylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Boston Pharmaceuticals, Bristol-Meyers Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse Bio, Hightide, Inipharma, Intercept, Inventiva, Ionis, Janssen Inc., Madrigal, Metacrine, Inc., NGM Biopharmaceuticals, Novartis, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89bio, Terns Pharmaceuticals and Viking Therapeutics; Grants: Arrowhead Pharmacetuicals, AstraZeneca, Boegringer-Ingelheim, Bristol-Meyers Squibb, Eli Lilly, Galectin Therapeutics, Galmeed Pharmaceuticals, Gilead, Hanmi, Intercept, Inventiva, Ionis, Janssen, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, Novo Nordisk, Pfizer, Sonic Incytes and Terns Pharmaceuticals; Stockholder: Co-founder LipoNexus, Inc
Mildred D Gottwald, Shibao Feng, Germaine D Agollah, Cynthia L Hartsfield, Hank Mansbach, Maya Margalit: 89bio employee and stock holder