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Comparative Study
. 2025 Jun;42(6):2708-2727.
doi: 10.1007/s12325-025-03183-x. Epub 2025 May 6.

One-Year Efficacy of Guselkumab Versus Advanced Therapies for the Treatment of Moderately to Severely Active Crohn's Disease: A Network Meta-Analysis

Tim Disher  1 , Dominik Naessens  2 , Myrlene Sanon  3 , Ashley Bonner  1 , Jenna Ellis  1 , Meaghan Bartlett  1 , Becky Hooper  1 , Zijiang Yang  4 , Jessica R Allegretti  5 , Axel Dignass  6
Affiliations
Comparative Study

One-Year Efficacy of Guselkumab Versus Advanced Therapies for the Treatment of Moderately to Severely Active Crohn's Disease: A Network Meta-Analysis

Tim Disher et al. Adv Ther. 2025 Jun.

Abstract

Introduction: This study used network meta-analysis (NMA) to evaluate the comparative efficacy of available advanced therapies for moderately to severely active Crohn's disease (CD) versus the IL-23 inhibitor guselkumab.

Methods: A systematic literature review was conducted to identify randomized controlled trials (RCTs) of advanced therapies in moderately to severely active CD. Bayesian NMAs were conducted for outcomes of clinical response, clinical remission, endoscopic response, and a combined outcome of clinical remission with endoscopic response, at the end of the maintenance phase (up to 1 year). Primary analyses included patients with varied prior inadequate treatment responses, with additional analyses conducted for specific subgroups. Re-randomized trials were normalized in several cases to mimic a standard treat-through design, incorporating data from additional sources, when necessary, for patients who had an inadequate response or experienced a delayed response following induction.

Results: Of the 58 RCTs identified, 13 with maintenance endpoint data were ultimately included in the NMAs. Guselkumab 100 mg and 200 mg were more likely to be effective versus several comparators. Guselkumab 200 mg demonstrated significantly greater efficacy versus infliximab 10 mg/kg every 8 weeks and upadacitinib 30 mg daily for clinical response and clinical remission. For endoscopic response, guselkumab 200 mg showed significantly greater efficacy than ustekinumab, adalimumab, and upadacitinib. Significance was also noted versus ustekinumab on the combined outcome of clinical remission with endoscopic response. Similarly, guselkumab 100 mg demonstrated efficacy versus comparators across analyses. Guselkumab achieved higher rankings based on surface under the cumulative ranking curve. Findings of primary analyses within mixed populations were generally corroborated by subpopulation analyses.

Conclusion: Results of this NMA in moderately to severely active CD indicate a higher likelihood of guselkumab achieving each clinical and endoscopic endpoint analyzed at the end of the maintenance phase versus other advanced therapies assessed.

Keywords: Biologics; Crohn’s disease; Guselkumab; Indirect treatment comparisons; Network meta-analysis; Study design.

Plain language summary

A network meta-analysis (NMA) was completed to compare the effectiveness of advanced treatments for Crohn’s disease, a chronic inflammatory condition of the digestive tract. Our NMA focused on the drug guselkumab and how effective it is compared with other treatments for Crohn’s disease. We looked at 4 outcomes related to efficacy that are common in trials: clinical response (improvement in symptoms), clinical remission (disappearance of symptoms), endoscopic response (seen in the digestive tract), and a combined outcome of clinical remission with endoscopic response. Data were analyzed from trials lasting up to 1 year. Patients who had not responded well to prior treatments were included in the analysis. Thirteen trials met all criteria and were included in the analysis. Guselkumab at doses of 100 mg and 200 mg was more effective than several treatments. Guselkumab 200 mg was significantly better than infliximab and upadacitinib for both clinical response and clinical remission. It also showed better results than ustekinumab, adalimumab, and upadacitinib for endoscopic response and was more effective than ustekinumab for the combined outcome of clinical remission with endoscopic response. Our analysis shows that guselkumab is likely to be more effective at achieving both symptom improvement and healing the digestive tract compared with other advanced treatments for moderate to severe Crohn’s disease.

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Conflict of interest statement

Declarations. Conflicts of Interest: Tim Disher, Meaghan Bartlett, Becky Hooper, Jenna Ellis, and Ashley Bonner are current or former employees of EVERSANA. Myrlene Sanon, Dominik Naessen, and Zijiang Yang are employees of Johnson & Johnson and may hold stock/stock options in Johnson & Johnson. Drs. Axel Dignass and Jessica R. Allegretti have received personal compensation from Janssen for consultant fees. Axel Dignass reports fees for participation in clinical trials, review activities such as data monitoring boards, statistical analysis, and endpoint committees from Abivax, AbbVie, Bristol Myers Squibb, Dr Falk Pharma, Galapagos, Gilead, Janssen, and Pfizer; consultancy fees from AbbVie, Amgen, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Dr Falk Foundation, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos, J&J, Lilly, MSD, Pfizer, Pharmacosmos, Sandoz, Stada, Takeda, Tillotts, and Vifor Pharma; payment from lectures including service on speakers bureaus from AbbVie, Biogen, CED Service GmbH, Celltrion, Falk Foundation, Ferring, Galapagos, Gilead, High5MD, Janssen, Materia Prima, MedToday, MSD, Pfizer, Streamed-Up, Takeda, Tillotts, and Vifor Pharma; and payment for manuscript preparation from Falk Foundation, Takeda, Thieme, and UniMed Verlag. Preparation of this manuscript was funded by Janssen. Ethical Approval: This analysis and summary are based on previously completed/published trials and do not contain any new studies with human participants or animals performed by any of the authors.

Figures

Fig. 1
Fig. 1
Flow diagram of the study selection process. Qualitative synthesis refers to inclusion in the SLR, whereas quantitative synthesis refers to trials considered potentially eligible for NMA based on investigated treatment, regimen, and outcome reporting. CDSR Cochrane Database of Systematic Reviews, CENTRAL Cochrane Central Register of Controlled Trials, NMA network meta-analysis, SLR systematic literature review
Fig. 2
Fig. 2
a Evidence network for primary analyses and b league table for random effects NMAs of clinical response. Thickness of lines connecting distinct regimens reflects the number of trials informing distinct connections, where induction trials are excluded from trial labels. ADA adalimumab, CERT certolizumab pegol, GUS guselkumab, IFX infliximab, MIRI mirikizumab, NAT natalizumab, NMA network meta-analysis, PBO placebo, RIS risankizumab, UPA upadacitinib, UST ustekinumab, VDZ vedolizumab
Fig. 3
Fig. 3
Bar plot of SUCRA values for NMAs for all 4 outcomes across all treatments. Ordered by average of SUCRA values across outcomes. SUCRA values range from 0 to 1 and represent the percentage of efficacy that a treatment achieves relative to an ideal treatment. ADA adalimumab, CERT certolizumab pegol, CRm clinical remission, ER endoscopic response, GUS guselkumab, IFX infliximab, MIRI mirikizumab, NMA network meta-analysis, PBO placebo, RIS risankizumab, SUCRA surface under the cumulative ranking curve, UPA upadacitinib, UST ustekinumab, VDZ vedolizumab
Fig. 4
Fig. 4
a Evidence network for primary analyses and b league table for random effects NMAs of clinical remission. ADA adalimumab, CERT certolizumab pegol, GUS guselkumab, IFX infliximab, MIRI mirikizumab, NAT natalizumab, NMA network meta-analysis, PBO placebo, RIS risankizumab, UPA upadacitinib, UST ustekinumab, VDZ vedolizumab
Fig. 5
Fig. 5
a Evidence network for primary analyses and b league table for random effects NMAs of endoscopic response. ADA adalimumab, GUS guselkumab, MIRI mirikizumab, NMA network meta-analysis, PBO placebo, RIS risankizumab, UPA upadacitinib, UST ustekinumab
Fig. 6
Fig. 6
a Evidence network for primary analyses and b league table for random effects NMAs of combined clinical remission with endoscopic response outcome. ADA adalimumab, GUS guselkumab, MIRI mirikizumab, NMA network meta-analysis, PBO placebo, RIS risankizumab, UST ustekinumab
Fig. 7
Fig. 7
Forest plots for random effects NMAs of efficacy outcomes in mixed, BIO-IR, and non-BIO-IR populations. ADA adalimumab, BIO-IR inadequate response or intolerance to biologics, CERT certolizumab pegol, GUS guselkumab, IFX infliximab, MIRI mirikizumab, NAT natalizumab, NMA network meta-analysis, PBO placebo, Q4W every 4 weeks, RIS risankizumab, UPA upadacitinib, UST ustekinumab, VDZ vedolizumab
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References

    1. Saez A, Herrero-Fernandez B, Gomez-Bris R, Sanchez-Martinez H, Gonzalez-Granado JM. Pathophysiology of inflammatory bowel disease: innate immune system. Int J Mol Sci. 2023;24:1526. - PMC - PubMed
    1. Yang AZ, Jostins-Dean L. Environmental variables and genome-environment interactions predicting IBD diagnosis in large UK cohort. Sci Rep. 2022;12:10890. - PMC - PubMed
    1. Veauthier B, Hornecker JR. Crohn’s disease: diagnosis and management. Am Fam Physician. 2018;98:661–9. - PubMed
    1. Lichtenstein GR, Loftus EV, Isaacs KL, Regueiro MD, Gerson LB, Sands BE. ACG clinical guideline: management of Crohn’s disease in adults. Am J Gastroenterol. 2018;113:481–517. - PubMed
    1. Roda G, Chien Ng S, Kotze PG, et al. Crohn’s disease. Nat Rev Dis Primers. 2020;6:22. - PubMed

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