Skip Navigation
Skip to contents

Intest Res : Intestinal Research

Search
Advanced Search
IMPACT FACTOR
mobile search button mobile menu button

Articles

Page Path
HOME > Intest Res > Ahead-of print articles > Article
Original Article Guselkumab efficacy and safety in East Asian participants with moderately to severely active Crohn’s disease: subgroup analysis of the phase 3 GALAXI 2 and GALAXI 3 trials
Hiroshi Nakase1orcid, Baili Chen2orcid, Qian Cao3orcid, Katsuyoshi Matsuoka4orcid, Tadakazu Hisamatsu5orcid, Dong Il Park6orcid, Keira Herr7orcid, Bryan Wahking7orcid, Wai Chun Yiu8orcid, Jianmin Zhuo9orcid, Minhu Chen2orcid

DOI: https://doi.org/10.5217/ir.2025.00150
Published online: May 21, 2026

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan

2Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

3Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China

4Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Sakura Medical Center, Chiba, Japan

5Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Tokyo, Japan

6Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea

7Johnson & Johnson, Singapore

8Johnson & Johnson, Spring House, PA, USA

9Johnson & Johnson, Shanghai, China

Correspondence to Minhu Chen, Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan Er Road, Guangzhou 510080, China. E-mail: chenminhu@mail.sysu.edu.cn
• Received: July 22, 2025   • Revised: December 31, 2025   • Accepted: January 12, 2026

© 2026 Korean Association for the Study of Intestinal Diseases.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

  • 1,172 Views
  • 47 Download
Full Article

Download PDF Download PDF

  • Background/Aims
    Guselkumab, a dual-acting interleukin-23p19 subunit inhibitor, demonstrated efficacy and safety in participants with moderately to severely active Crohn’s disease in the global phase 3 GALAXI 2 and 3 trials. We report a subgroup analysis in East Asian participants.
  • Methods
    GALAXI 2 and 3 (NCT03466411) are identical, 48-week treat-through trials. Participants were randomized 2:2:2:1 to guselkumab 200 mg IV every 4 weeks (q4w; ×3), followed by 100 mg SC every 8 weeks (q8w) or 200 mg SC q4w; ustekinumab; or placebo. Placebo participants not in clinical response at week (W)12 received ustekinumab. Co-primary endpoints were the composite of clinical response at W12 and clinical remission at W48, and the composite of clinical response at W12 and endoscopic response at W48. This subgroup analysis included participants from China, Japan, South Korea, and Taiwan.
  • Results
    The East Asian subgroup included 192 participants. Rates of clinical response at W12 and clinical remission at W48 with guselkumab were 55.6% (100 mg SC q8w) and 51.0% (200 mg SC q4w) versus 3.1% with placebo. Rates of clinical response at W12 and endoscopic response at W48 with guselkumab were 44.4% (100 mg SC q8w) and 39.2% (200 mg SC q4w), versus 0% for placebo. Numerically higher proportions of guselkumab participants achieved clinical and endoscopic outcomes at W48 relative to ustekinumab. Adverse event rates were consistent with the global population.
  • Conclusions
    Efficacy of guselkumab in East Asian participants was consistent with that observed in the global GALAXI 2 and 3 population. The safety profile was favorable and consistent with previous reports.
  • Keywords: Asia; Clinical trial; Crohn disease; Guselkumab
Crohn’s disease (CD) is a chronic and debilitating inflammatory bowel disease (IBD) manifesting as discontinuous inflammatory lesions that can occur anywhere throughout the gastrointestinal tract [1,2]. While IBD is most prevalent in Western regions, notable increases in CD incidence and prevalence have occurred in industrialized regions in Asia in recent years [3-6]. Of note, differences in genotype and disease characteristics have been noted between Asian and Western patients with CD, including a male predominance and higher prevalence of perianal fistulas in Asians [5,7,8].
Pharmacological management of CD involves use of an induction and maintenance regimen to induce and maintain disease remission [1,2,9]. Despite the availability of conventional (e.g., corticosteroids, thiopurines, and methotrexate) and biologic (e.g., anti-tumor necrosis factor) therapies, many patients respond inadequately, lose response over time, or experience side effects that necessitate discontinuation [1,2]. There remains a need for additional pharmacotherapies with favorable efficacy and safety.
Guselkumab is a selective, dual-acting interleukin (IL)-23p19 subunit inhibitor that potently blocks IL-23 and binds to CD64 (cluster of differentiation 64), a receptor on immune cells that produce IL-23 [10]. The Phase 2/3 GALAXI program in people with moderately to severely active CD evaluated the efficacy and safety of guselkumab intravenous (IV) induction followed by subcutaneous (SC) maintenance therapy in 3 randomized, double-blind clinical trials employing a treat-through design. In the Phase 2 GALAXI 1 dose-ranging trial, participants receiving guselkumab IV induction and SC maintenance attained high rates of clinical and endoscopic efficacy endpoints [11]. In the identically designed, placebo- and active comparator (ustekinumab)-controlled phase 3 GALAXI 2 and 3 trials, guselkumab demonstrated efficacy versus placebo across clinical and endoscopic endpoints evaluating short-term (i.e., 12-week induction) and long-term (48-week maintenance) efficacy [12]. Guselkumab also demonstrated superiority versus ustekinumab against long-term efficacy endpoints at week 48.
Given the rising burden of CD in Asia and the potential differences in clinical manifestation noted above, it is important to characterize the safety and efficacy of novel CD therapeutics in Asian patients. Moreover, the higher prevalence of latent and active tuberculosis and hepatitis B virus complicates the management of CD in Asia [9,13,14]. Both GALAXI 2 and GALAXI 3 included study sites in East Asia (China, Japan, South Korea, and Taiwan region). We report a subgroup analysis of guselkumab efficacy and safety in East Asian participants from GALAXI 2 and 3.
1. Study Design and Participants
The global GALAXI 2 and 3 trials (NCT03466411) were conducted across 40 countries between January 8, 2020, and October 20, 2023. Details of the study design and participant eligibility criteria are reported elsewhere [12]. An overview of the study design is presented in Fig. 1. Eligible participants were adults (≥ 18 years of age) with moderately to severely active CD of at least 3 months’ duration (Crohn’s Disease Activity Index [CDAI] score of 220 to 450 and either mean daily stool frequency [SF] count > 3 or abdominal pain [AP] score > 1), a Simple Endoscopic Score for Crohn’s Disease (SES-CD) ≥ 6 (≥ 4 for isolated ileal disease) at screening, and inadequate response or intolerance to conventional or biologic therapy. Exclusion criteria included prior treatment with a biologic therapy targeting IL-12 or IL-23, except limited prior ustekinumab exposure at approved dosages and intervals with no evidence of inadequate response or intolerance.
The trials employed a treat-through design, whereby participants were randomized at week 0 and remained on the assigned treatment regimen through week 48. Participants were randomized in a 2:2:2:1 ratio to the following IV induction and SC maintenance regimens: guselkumab 200 mg IV every 4 weeks (q4w) at weeks 0, 4, and 8, followed by 100 mg SC every 8 weeks (q8w; guselkumab IV to 100 mg SC q8w); guselkumab 200 mg IV q4w at weeks 0, 4, and 8, followed by 200 mg SC q4w (guselkumab IV to 200 mg SC q4w); ustekinumab (approximately 6 mg/kg) IV at week 0 then 90 mg SC q8w; or placebo IV at weeks 0, 4, and 8. Placebo group participants not in clinical response (defined as ≥ 100-point decrease in CDAI score from baseline or achieving a CDAI score < 150) at week 12 received rescue treatment with ustekinumab (approximately 6 mg/kg IV at week 12 then 90 mg SC q8w).
The trial protocol was approved by an institutional review board or ethics committee at each participating site, including The First Affiliated Hospital, Sun Yat-sen University (IRB No. 2018-033-03). The trial was conducted in compliance with the Declaration of Helsinki, Good Clinical Practice guidelines, and applicable local regulations [12]. All participants provided written informed consent prior to any study procedures.
The East Asian subpopulation included all participants from study sites located in China, Japan, South Korea, and the Taiwan region. Country-specific subgroup data for participants from Japan are included in Supplementary Table 1 and Supplementary Fig. 1.
2. Outcome Assessments and Endpoint Definitions
Efficacy assessments included symptom-based, endoscopic, and biomarker components. For evaluation of clinical response and remission, the CDAI components were assessed at each study visit (q4w), and a CDAI score was calculated if at least 4 of 8 components were available. Clinical response was defined as a ≥ 100-point reduction from baseline in CDAI score or a CDAI score < 150. Clinical remission was defined as a CDAI score < 150 (corticosteroid-free clinical remission: clinical remission with no receipt of corticosteroids for 90 days before the indicated timepoint). Remission based on the 2 patient-reported outcome (PRO) components of the CDAI (i.e., PRO-2 remission) was defined as AP mean daily score ≤ 1 and SF mean daily score ≤ 3 and no worsening of AP or SF from baseline. For evaluation of endoscopic endpoints, video endoscopic assessments of the terminal ileum and colon were done at screening and at weeks 12 and 48 and scored by blinded central readers using the SES-CD. Endoscopic response was defined as ≥ 50% improvement from baseline in SES-CD score or SES-CD score ≤ 2, while endoscopic remission was defined as SES-CD score ≤ 4, ≥ 2-point reduction from baseline, and no SES-CD subscore > 1 in any individual component.
Fatigue was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 7a (SF-7a) at baseline and at weeks 8, 12, 24, and 48. Fatigue response was defined as a ≥ 7-point improvement from baseline in PROMIS Fatigue SF-7a score. For biomarker assessments, C-reactive protein (CRP) measurements were performed q4w through week 24 and q8w thereafter. Fecal calprotectin assessments were done at baseline and at weeks 4, 8, 12, 24, and 48.
The efficacy outcomes in GALAXI 2 and 3 were designed to assess short-term and long-term components. The composite co-primary endpoints compared guselkumab versus placebo based on (1) clinical response at week 12 and clinical remission at week 48 and (2) clinical response at week 12 and endoscopic response at week 48. Major secondary endpoints evaluating the short-term efficacy of guselkumab IV induction versus placebo (at week 12 unless otherwise noted) included clinical remission, endoscopic response, the composite of clinical remission and endoscopic response, fatigue response, and clinical response at week 4. Major secondary endpoints further assessing the short- and long-term efficacy of guselkumab (at week 12 and week 48) were (1) the composite of clinical response at week 12 and corticosteroid-free clinical remission at week 48 and (2) the composite of clinical response at week 12 and endoscopic remission at week 48. Finally, major secondary outcomes designed to evaluate the long-term efficacy of guselkumab SC maintenance versus ustekinumab at week 48 included clinical remission, endoscopic response, endoscopic remission, deep remission (clinical remission and endoscopic remission), and the composite of clinical remission and endoscopic response. PRO-2 remission was evaluated as an additional endpoint. Supplemental analyses were done in subpopulations based on CD medication history.
Safety was evaluated based on treatment-emergent adverse event (TEAE) reporting, infections, physical examinations, clinical laboratory tests, and vital signs. Levels of serum anti-drug antibodies were determined q4w through week 12 then q8w from week 24 using validated assays.
3. Statistical Analysis
Details of the primary analyses in the global GALAXI 2 and 3 populations are reported elsewhere [12]; we describe a subgroup analysis using pooled GALAXI 2 and 3 data for East Asian participants. The efficacy and safety analyses were based on the primary analysis set of randomized participants who received ≥ 1 (partial or complete) dose of study intervention and had a screening SES-CD score ≥ 6 (or ≥ 4 for isolated ileal disease). Data are summarized descriptively. Subgroup analyses were not preplanned with alpha control in the original study design. No statistical comparisons between treatment cohorts were made for these subgroup analyses. Pooled GALAXI 2 and 3 data were also included in the supplementary analyses of Japanese participants.
1. Participants: East Asian Subgroup
Of the 1,021 participants included in the pooled primary analysis set population of the global GALAXI 2 and 3 trials, 192 (98 GALAXI 2 and 94 GALAXI 3) were from sites located in East Asia and were included in the present subgroup analysis (118 China, 48 Japan, 23 South Korea, and 3 Taiwan region). Thirteen East Asian participants discontinued trial participation prior to week 48, most commonly due to participant withdrawal (Fig. 2).
Baseline demographic and disease characteristics were generally similar across treatment groups of East Asian participants (Table 1). Overall, 18.8% (36/192) of East Asian participants were naive to biologic therapy, while 74.0% (142/192) had a history of intolerance or inadequate response to prior biologic therapy. As observed for the global population [12], the proportion of participants with ileal-only disease was higher in the guselkumab IV to 200 mg SC q4w group compared with other treatment groups.
Relative to the global GALAXI 2 and 3 population, the East Asian subgroup included more men, fewer participants with SF count > 3, fewer participants with ileum-only disease, and more participants with ileocolonic disease (Supplementary Table 2). Mean age (33.5 years) and body weight (58.0 kg) were lower for the East Asian subgroup relative to the global population (36.5 years; 68.2 kg).
2. Short-Term and Long-Term Guselkumab Efficacy in East Asian Participants
Consistent with findings in the global trials [12], numerically greater proportions of East Asian participants in both guselkumab cohorts achieved composite efficacy endpoints with both a short-term (week 12) and long-term (week 48) component relative to placebo participants (Fig. 3). In the East Asian subpopulation, 35/63 (55.6%) guselkumab IV to 100 mg SC q8w participants and 26/51 (51.0%) guselkumab IV to 200 mg SC q4w participants achieved the co-primary endpoint of clinical response at week 12 and clinical remission at week 48 compared with 1/32 (3.1%) placebo participants (Fig. 3A). These rates were similar to those observed in the global GALAXI 2 and 3 population (guselkumab IV to 100 mg SC q8w: 47.9%; guselkumab IV to 200 mg SC q4w: 51.4%; placebo: 12.2%) [12]. For the composite co-primary endpoint of clinical response at week 12 and endoscopic response at week 48, the response rate was 28/63 (44.4%) among East Asian guselkumab IV to 100 mg SC q8w participants and 20/51 (39.2%) among guselkumab IV to 200 mg SC q4w participants compared with 0/32 placebo participants (Fig. 3B). Responses in the East Asian subgroup were broadly consistent with those observed for the global population (guselkumab IV to 100 mg SC q8w: 36.4%; guselkumab IV to 200 mg SC q4w: 37.2%; placebo: 5.4%) [12]. Numerically higher proportions of East Asian participants receiving guselkumab also achieved the composite major secondary outcomes evaluating short- and long-term efficacy relative to placebo based on clinical response at week 12 and 90-day corticosteroid-free clinical remission at week 48 (Fig. 3C) and clinical response at week 12 and endoscopic remission at week 48 (Fig. 3D). Relative to global participants, placebo response rates tended to be numerically lower and guselkumab response rates higher among East Asian participants across these efficacy endpoints.
Rates of attaining secondary endpoints designed to evaluate the short-term efficacy of guselkumab IV induction are summarized in Table 2. East Asian participants receiving guselkumab 200 mg IV achieved numerically higher rates of clinical remission, fatigue response, endoscopic response, and the composite of clinical remission and endoscopic response at week 12 compared with placebo participants. Placebo rates were generally lower for East Asians compared with the global population. In the guselkumab group, rates of attaining week 12 efficacy endpoints were similar between the East Asian subgroup and the global population.
CDAI scores generally decreased (indicating improvement) over time from week 4 through week 48 in East Asian guselkumab participants (Fig. 4A). Clinical and PRO-2 remission rates likewise increased throughout the trial period in guselkumab participants from approximately 10% to 30% at week 4 to > 60% by week 48 (Fig. 4B and C).
Rates of attaining secondary endpoints evaluating the long-term efficacy of guselkumab SC maintenance treatment relative to the active comparator ustekinumab at week 48 are summarized in Fig. 5. Numerically higher proportions of East Asian guselkumab versus ustekinumab participants achieved endoscopic response, endoscopic remission, the composite of clinical remission and endoscopic response, and deep remission (composite of clinical remission and endoscopic remission) at week 48. Response rates among East Asian participants were similar to the corresponding rates in the global GALAXI 2 and 3 population [12].
The effects of guselkumab relative to ustekinumab on biomarkers of disease activity (CRP and fecal calprotectin concentrations) in East Asian participants are presented in Supplementary Figs. 2 and 3. Among participants with elevated CRP (> 3 mg/L) concentrations at baseline, approximately 55% of guselkumab-treated participants had normal CRP levels (i.e., ≤ 3 mg/L) at week 48. Among those with elevated fecal calprotectin levels (> 250 µg/g) at baseline, approximately 41% of guselkumab-treated participants achieved normal levels (i.e., ≤ 250 µg/g) by week 48.
Efficacy of guselkumab in East Asian participants was generally consistent across subgroups with a history of inadequate response or intolerance to biologic therapies, inadequate response to prior conventional therapy, and those without prior exposure to biologic therapies; however, participant numbers in these subgroups were small (Supplementary Tables 3-5).
3. Safety in East Asian Participants
Table 3 summarizes TEAEs reported in East Asian and global GALAXI 2 and 3 trial participants. In the East Asian subpopulation, TEAEs were reported in 55/63 (87.3%) participants in the guselkumab IV to 100 mg SC q8w group, 46/51 (90.2%) in the guselkumab IV to 200 mg SC q4w group, 23/32 (71.9%) in the placebo group (excluding events after ustekinumab crossover), and 41/46 (89.1%) in the ustekinumab group through week 48 (Table 3). The rates of TEAEs in East Asian participants were numerically higher than in the global population in all treatment groups, including the placebo group (guselkumab IV to 100 mg SC q8w: 219/286 [76.6%]; guselkumab IV to 200 mg SC q4w: 230/296 [77.7%]; placebo: 79/148 [53.4%]; ustekinumab: 229/291 [78.7%]).
The most common TEAEs reported in East Asian guselkumab participants were coronavirus disease 2019, upper respiratory tract infections, and arthralgia (Supplementary Table 6). Placebo participants experienced higher rates of TEAEs of CD worsening (3/32 [9.4%], excluding events after crossover to ustekinumab) relative to guselkumab and ustekinumab group participants (guselkumab IV to 100 mg SC q8w: 0/63; guselkumab IV to 200 mg SC q4w: 3/51 [5.9%]; ustekinumab: 2/46 [4.3%]). Frequencies and types of common TEAEs were generally consistent between East Asian and global trial participants, with some exceptions (e.g., upper respiratory tract infections and pyrexia were more common among East Asians).
Serious TEAEs were reported in 11 East Asian participants with guselkumab (guselkumab IV to 100 mg SC q8w: 7 [11.1%]; guselkumab IV to 200 mg SC q4w: 4 [7.8%]), 5 (15.6%) placebo participants, and 6 (13.0%) ustekinumab participants (Table 3, Supplementary Table 7). Rates of serious TEAEs were similar in East Asian and global participants (Table 3). Most of the serious events reported in the East Asian subpopulation fell under the Medical Dictionary for Regulatory Activities system organ class of gastrointestinal disorders (guselkumab: 9 [7.9%]; placebo: 4 [12.5%]; ustekinumab: 4 [8.7%]) (Supplementary Table 7). Two guselkumab participants (guselkumab IV to 100 mg SC q8w: 1 [1.6%]; guselkumab IV to 200 mg SC q4w: 1 [2.0%]) experienced serious TEAEs of intestinal obstruction; no other serious TEAEs were reported in more than 1 guselkumab participant. Serious TEAEs of worsening CD were more frequent among placebo participants (2 [6.3%]) relative to guselkumab participants (1 [0.9%]).
Nine East Asian participants in the guselkumab groups (guselkumab IV to 100 mg SC q8w: 3 [4.8%]; guselkumab IV to 200 mg SC q4w: 6 [11.8%]), 3 (9.4%) placebo participants, and 2 (4.3%) ustekinumab participants discontinued study agent due to TEAEs (Table 3). Rates of TEAEs leading to discontinuation of study agent were similar to those reported in the global population (Table 3). Details of individual TEAEs leading to discontinuation of study agent in East Asian participants are summarized in Supplementary Table 7. Discontinuation due to TEAEs of worsening CD was more common in placebo participants (2 [6.3%]) relative to guselkumab participants (1 [0.9%]). No deaths were reported among East Asian participants.
Infections were reported in 36/63 (57.1%) participants in the guselkumab IV to 100 mg SC q8w group, 28/51 (54.9%) in the guselkumab IV to 200 mg SC q4w group, 8/32 (25.0%) in the placebo group (excluding events after ustekinumab crossover), and 24/46 (52.2%) in the ustekinumab group (Table 3). Rates of infection were generally similar to observations in the global population. Among East Asian participants, no serious infections or cases of tuberculosis were reported in guselkumab group participants.
Among East Asian participants with samples suitable for immunogenicity assessments, 1/63 (1.6%) guselkumab IV to 100 mg SC q8w and 8/50 (16.0%) guselkumab IV to 200 mg SC q4w participants had antibodies to guselkumab through week 48. Neutralizing antibodies were detected in 1 participant (in the guselkumab IV to 100 mg SC q8w group). Due to the low number of participants testing positive for antibodies to guselkumab, the relationship between anti-drug antibodies and efficacy or safety could not be assessed.
Safety data for the subgroup of participants from Japan are summarized in Supplementary Table 1.
In this subgroup analysis, efficacy and safety of guselkumab induction and maintenance therapy in East Asian participants with moderately to severely active CD were generally consistent with observations in the global GALAXI 2 and 3 trial population [12]. Across clinical and endoscopic endpoints designed to assess both short- and long-term efficacy, East Asian guselkumab participants achieved higher response rates compared with placebo participants. For long-term endoscopic outcomes, response rates also tended to be numerically higher with guselkumab relative to the ustekinumab group. These results underscore the efficacy of guselkumab against endoscopic outcomes, which are used as objective treatment targets to guide clinical decision-making. Moreover, East Asian participants receiving guselkumab had high rates of achieving composite endpoints that included symptom and endoscopic improvements in a single participant, which are considered more clinically meaningful than endpoints separately evaluating symptomatic and objective improvements.
Response rates in East Asian participants were generally similar to those observed in the global population, in which statistically significant efficacy was demonstrated [12]. However, placebo response rates for some endpoints were lower in the East Asian subpopulation compared with rates in the global population. In addition, for the composite endpoints evaluating the short- and long-term efficacy of guselkumab at week 12 and week 48, numerically higher guselkumab response rates were generally observed among East Asian relative to global participants. The difference was particularly notable for the guselkumab IV to 100 mg SC q8w group.
Consistent with observations in the global population [12], there was no apparent dose-related correlation with regard to efficacy of the guselkumab 200 mg SC q4w and 100 mg SC q8w regimens.
GALAXI 2 and 3 included biologic-naïve participants as well as participants with a history of inadequate response or intolerance to biologic therapy. Efficacy response rates favored guselkumab in East Asian participants across subgroups stratified by prior biologic therapy. However, as expected, higher response rates were generally observed in the biologic-naïve participants, emphasizing the potential benefit of earlier guselkumab treatment
Although differences in participant backgrounds and study design limit cross-study comparisons, the clinical and endoscopic response rates with guselkumab induction and maintenance therapy among East Asian and global participants from GALAXI 2 and 3 are favorable in the context of observations from phase 3 studies of induction and maintenance regimens of other anti-IL-23 antibodies and the Janus kinase inhibitor upadacitinib [15-17]. For example, the phase 3 VIVID 1 study of the anti-IL-23 antibody mirikizumab was designed similarly to GALAXI 2 and 3 in that the study employed a treat-through design and ustekinumab comparator arm [16]. However, mirikizumab was not superior to ustekinumab against long-term secondary endpoints (at week 52) in VIVID 1.
Guselkumab was well tolerated in East Asian participants, with no unexpected safety findings. The safety profile of guselkumab was similar across the 2 maintenance dose regimens (i.e., 200 mg SC q4w and 100 mg SC q8w). Rates and types of TEAEs were generally consistent with observations from the global GALAXI 2 and 3 population [12].
Study limitations should be considered in interpreting these findings. This was a subgroup analysis of a global trial. Since there was no preplanned alpha control for the East Asian subpopulation in the trial design, statistical comparisons were not made between treatment cohorts. The number of East Asian participants was limited; however, a clear benefit in favor of guselkumab across efficacy endpoints was observed.
Overall, these results support the efficacy and safety of guselkumab induction and maintenance therapy in East Asian participants with CD, consistent with findings from the global GALAXI clinical trial program.

Funding Source

This study was supported by Johnson & Johnson.

Conflict of Interest

Nakase H reports receiving personal fees from AbbVie Inc., Kissei Pharmaceutical Co., Ltd., KYORIN Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Janssen Pharmaceutical K.K., Takeda Pharmaceutical Co., Ltd., Pfizer Japan Inc., EA Pharma Co., Ltd., Mochida Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Gilead Sciences Inc., and VIATRIS Inc., JIMRO Co., Ltd., and grants for commissioned/joint research from Hoya Group Pentax Medical, Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., and AbbVie Inc. He has endowed chair by Miyarisan Pharmaceutical Co., Mochida Pharmaceutical Co., Ltd., JIMRO Co., Ltd., and KYORIN Pharmaceutical Co., Ltd. Cao Q served as a steering committee adviser for Bristol Myers Squibb Company and Janssen Research Development, LLC and has received research grants from Johnson & Johnson and Takeda Pharmaceutical Co., Ltd. Matsuoka K reports potential conflicts of interest with Janssen, AbbVie Inc., Takeda Pharmaceutical Co., Ltd., Pfizer Inc., Gilead, Eli Lilly, Mitsubishi Tanabe Pharma, EA Pharma Co., Ltd., Mochida Pharmaceutical Co., Ltd., Kyorin, Zeria, Nippon Kayaku Co., Ltd., JIMRO, and Celltrion Healthcare. Hisamatsu T reports grant support from AbbVie GK, Boston Scientific Corporation, EA Pharma Co., Ltd., JIMRO Co., Ltd., Kissei Pharmaceutical Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Pfizer Inc., Takeda Pharmaceutical Co., Ltd., and Zeria Pharmaceutical Co., Ltd.; consulting fees from AbbVie GK, Bristol Myers Squibb, EA Pharma Co., Ltd., Eli Lilly, Gilead Sciences, Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corporation, and Pfizer Inc.; and lecture fees from AbbVie GK, EA Pharma Co., Ltd., Janssen Pharmaceutical K.K., JIMRO Co., Kissei Pharmaceutical Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Pfizer Inc., and Takeda Pharmaceutical Co., Ltd. Herr K, Wahking B, Yiu WC, and Zhuo J are employees of Johnson & Johnson and may own company stock/stock options. Chen M received research grants and served as a steering committee adviser for Johnson & Johnson Company, received lecture fees from Johnson & Johnson, Takeda, AbbVie Inc., and China Medical System Holding Limited. Except for the disclosures listed above, no other potential conflicts of interest relevant to this article were reported.

Hiroshi Nakase, Katsuyoshi Matsuoka, and Dong Il Park are members of the Editorial Board of this journal but were not involved in the peer review or decision-making process for this manuscript.

Data Availability Statement

The data sharing policy of Johnson & Johnson is available at https://innovativemedicine.jnj.com/our-innovation/clinicaltrials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access [YODA] Project site at http://yoda.yale.edu.

Author Contributions

Conceptualization: Herr K, Wahking B, Yiu WC. Formal analysis: Zhuo J. Investigation: Nakase H, Chen B, Cao Q, Matsuoka K, Hisamatsu T, Park DI, Chen M. Data curation: Zhuo J. Supervision: Chen M. Writing–original draft: Wahking B, Zhuo J. Writing–review & editing: all authors. Approval of final manuscript: all authors.

Additional Contributions

We are grateful to the participants and their families as well as the GALAXI investigators and site personnel. Medical writing assistance was provided by Erin Bekes, PhD, of Certara under the direction of the authors in accordance with Good Publication Practice guidelines. This assistance was funded by Johnson & Johnson.

Supplementary materials are available at the Intestinal Research website (https://www.irjournal.org).

Supplementary Table 1.

Summary of TEAEs Through Week 48 in Japanese Participants from the Pooled GALAXI 2 and 3 Studies
ir-2025-00150-Supplementary-Table-1.pdf

Supplementary Table 2.

Baseline Demographic and Disease Characteristics in GALAXI 2 and 3 (East Asian Subpopulation and Global Population)a
ir-2025-00150-Supplementary-Table-2.pdf

Supplementary Table 3.

Composite Week 12 and Week 48 Efficacy Endpoints in East Asian Participants from GALAXI 2 and 3 by Biologic Failure Status
ir-2025-00150-Supplementary-Table-3.pdf

Supplementary Table 4.

Short-Term (Week 4 and Week 12) Efficacy Endpoints in East Asian Participants from GALAXI 2 and 3 by Biologic Failure Status
ir-2025-00150-Supplementary-Table-4.pdf

Supplementary Table 5.

Long-Term (Week 48) Efficacy Endpoints in East Asian Participants from GALAXI 2 and 3 by Biologic Failure Status
ir-2025-00150-Supplementary-Table-5.pdf

Supplementary Table 6.

Summary of Most Common TEAEs (Reported in >5% of Participants in Any Treatment Group) Through Week 48 in the Pooled GALAXI 2 and 3 Population (East Asian Subpopulation and Global Population)a
ir-2025-00150-Supplementary-Table-6.pdf

Supplementary Table 7.

Summary of Serious TEAEs and TEAEs Leading to Treatment Discontinuation Through Week 48 by MedDRA SOC and PT (East Asian Subpopulation)
ir-2025-00150-Supplementary-Table-7.pdf

Supplementary Fig. 1.

Summary of guselkumab efficacy endpoints in Japanese participants from GALAXI 2 and 3 based on (A) composite endpoints with a short-term (W12) and long-term (W48) component, (B) short-term (W4 and W12) endpoints, and (C) long-term (W48) endpoints. Handling of missing data: Participants who had a CD-related surgery, a prohibited change in concomitant CD medication, or discontinued study agent due to lack of efficacy or an AE of worsening CD or discontinued study agent for any other reason other than COVID-19-related reasons or regional crisis prior to the analysis timepoint were considered not to have met the endpoint criteria. Participants who had discontinued study agent due to COVID-19-related reasons (excluding COVID-19 infection) or regional crisis had their observed data used, if available, to determine responder and nonresponder status at W12 and W48. After accounting for these cases, those who were missing endpoint data at W12 or W48 were considered not having achieved the endpoint. The “GUS 200 mg IV” group includes participants assigned to either GUS group; at the W12 assessment, GUS participants had received only GUS 200 mg IV. Clinical response is defined as ≥100-point reduction from baseline in CDAI score or CDAI score <150. Clinical remission is defined as CDAI score <150. Endoscopic response is defined as ≥50% improvement from baseline in SES-CD score or SES-CD score ≤2. Corticosteroid-free clinical remission is defined as CDAI score <150 and not receiving corticosteroids for at least 90 days prior to W48. Endoscopic remission is defined as SES-CD score ≤4 and at least a 2-point reduction from baseline and no subscore greater than 1 in any individual component. Fatigue response is defined as improvement of ≥7 points in PROMIS Fatigue Short Form 7a. Deep remission is defined as achieving both clinical remission and endoscopic remission. W, week; GUS, guselkumab; IV, intravenous; SC, subcutaneous; q8w, every 8 weeks; q4w, every 4 weeks; CD, Crohn’s disease; AE, adverse event; COVID-19, coronavirus disease 2019; CDAI, Crohn’s Disease Activity Index; SES-CD, Simplified Endoscopic Activity Score for Crohn’s Disease; PROMIS, Patient-Reported Outcomes Measurement Information System.
ir-2025-00150-Supplementary-Fig-1.pdf

Supplementary Fig. 2.

CRP responses to study intervention in East Asian participants from GALAXI 2 and 3 based on (A) median CRP concentrations through W48 and (B) normalization of CRP (≤3 mg/L) at W48 in participants with abnormal CRP (>3 mg/L) at baseline. The “GUS 200 mg IV” group includes participants assigned to either GUS group; GUS participants had received only GUS 200 mg IV through W12. CRP, C-reactive protein; UST, ustekinumab; IV, intravenous; GUS, guselkumab; SC, subcutaneous; q8w, every 8 weeks; q4w, every 4 weeks; W, week.
ir-2025-00150-Supplementary-Fig-2.pdf

Supplementary Fig. 3.

Fecal calprotectin responses to study intervention in East Asian participants from GALAXI 2 and 3 based on (A) median fecal calprotectin concentrations through W48 and (B) normalization of fecal calprotectin (≤250 µg/g) at W48 in participants with abnormal fecal calprotectin (>250 µg/g) at baseline. The “GUS 200 mg IV” group includes participants assigned to either GUS group; GUS participants had received only GUS 200 mg IV through W12. UST, ustekinumab; GUS, guselkumab; IV, intravenous; SC, subcutaneous; q8w, every 8 weeks; q4w, every 4 weeks; W, week.
ir-2025-00150-Supplementary-Fig-3.pdf
Fig. 1.
Overview of GALAXI 2 and 3 trial design. aBiologic therapies: tumor necrosis factor antagonists or vedolizumab. To maintain treatment masking, all participants received active and/or placebo IV q4w through week 12 and active or placebo SC q4w through week 48. CDAI, Crohn’s Disease Activity Index; SF, stool frequency; AP, abdominal pain; SES-CD, Simple Endoscopic Score for Crohn’s Disease; 6-MP, 6-mercaptopurine; AZA, azathioprine; MTX, methotrexate; GUS, guselkumab; IV, intravenous; q4w, every 4 weeks; q8w, every 8 weeks; SC, subcutaneous; UST, ustekinumab.
ir-2025-00150f1.jpg
Fig. 2.
Participant disposition in GALAXI 2 and 3 for the East Asian subpopulation. aParticipants who did not receive a maintenance dose and those who received placebo SC during the maintenance period; bParticipants who were not in clinical response to placebo induction dosing and crossed over to UST at W12 and continued to receive UST SC dosing in the maintenance period. GUS, guselkumab; IV, intravenous; SC, subcutaneous; q8w, every 8 weeks; q4w, every 4 weeks; UST, ustekinumab; W, week.
ir-2025-00150f2.jpg
Fig. 3.
Proportions of participants achieving the composite primary (A, B) and major secondary (C, D) endpoints assessing short-term (W12) and long-term (W48) efficacy of guselkumab in the GALAXI 2 and 3 trials (East Asian subpopulation and global population).a Handling of missing data: participants who had a CD-related surgery; had a prohibited change in concomitant CD medication (including placebo participants in clinical response who crossover to ustekinumab at W12); discontinued study agent due to lack of efficacy, an AE of worsening CD, or W20/24 nonresponder; or discontinued study agent for any other reason other than COVID-19-related reasons or regional crisis prior to the analysis timepoint were considered not to have met the endpoint criteria. Participants who had discontinued study agent due to COVID-19-related reasons (excluding COVID-19 infection) or regional crisis had their observed data used, if available, to determine responder and nonresponder status at W12 and W48. After accounting for the above, participants who were missing CDAI score at W12 or CDAI or SES-CD score at W48 were considered not to have achieved the relevant endpoint. aData for global participants have been reported previously [12]; bClinical response is defined as ≥100-point reduction from baseline in CDAI score or CDAI score <150; cClinical remission is defined as CDAI score <150; dEndoscopic response is defined as ≥50% improvement from baseline in SES-CD score or SES-CD score ≤2; eCorticosteroid-free clinical remission is defined as clinical remission with no receipt of corticosteroids for 90 days before indicated timepoint; fEndoscopic remission (global definition) is defined as SES-CD score ≤4 and at least a 2-point reduction from baseline and no subscore greater than 1 in any individual component. W, week; GUS, guselkumab; IV, intravenous; SC, subcutaneous; q8w, every 8 weeks; q4w, every 4 weeks; CD, Crohn’s disease; AE, adverse event; COVID-19, coronavirus disease 2019; CDAI, Crohn’s Disease Activity Index; SES-CD, Simple Endoscopic Score for Crohn’s Disease.
ir-2025-00150f3.jpg
Fig. 4.
Plots of change from baseline in CDAI scores (A), clinical remission rates (B) and PRO-2 remission rates (C) through W48 in GALAXI 2 and 3 (East Asian subpopulation). Handling of missing data: Participants who had a CD-related surgery, a prohibited change in concomitant CD medication, or discontinued study agent due to lack of efficacy, an AE of worsening CD, or W20/24 nonresponder or discontinued study agent for any other reason other than COVID-19-related reasons or regional crisis prior to the analysis timepoint were considered not to have met the endpoint criteria. Participants who had discontinued study agent due to COVID-19-related reasons (excluding COVID-19 infection) or regional crisis had their observed data used, if available, to determine responder and nonresponder status from that timepoint onwards. After accounting for the above, participants who were missing relevant scores at the designated analysis time-point were considered not to have achieved the endpoint at that timepoint. Clinical remission is defined as CDAI score <150. PRO-2 remission is defined as AP mean daily score at or below 1 and SF mean daily score at or below 3, and no worsening of AP or SF from baseline. CDAI, Crohn’s Disease Activity Index; GUS, guselkumab; IV, intravenous; SC, subcutaneous; q8w, every 8 weeks; q4w, every 4 weeks; PRO-2, patient-reported outcome-2; W, week; CD, Crohn’s disease; AE, adverse event; COVID-19, coronavirus disease 2019; AP, abdominal pain; SF, stool frequency.
ir-2025-00150f4.jpg
Fig. 5.
Summary of proportions of participants achieving endoscopic response (A), endoscopic remission (B), the composite of clinical remission and endoscopic response (C), and deep remission (D) at W48 in GALAXI 2 and 3 (East Asian subpopulation and global population). Data for global participants have been reported previously [12]. Handling of missing data: Participants who had a CD-related surgery, a prohibited change in concomitant CD medication, or discontinued study agent due to lack of efficacy, an AE of worsening CD, or W20/24 nonresponder or discontinued study agent for any other reason other than COVID-19-related reasons or regional crisis prior to the analysis timepoint were considered not to have met the endpoint criteria. Participants who had discontinued study agent due to COVID-19-related reasons (excluding COVID-19 infection) or regional crisis had their observed data used, if available. After accounting for the above, participants who were missing endpoint data at the indicated timepoint were considered not to have achieved the relevant endpoint. aEndoscopic response is defined as ≥50% improvement from baseline in SES-CD score or SES-CD score ≤2; bEndoscopic remission (global definition) is defined as SES-CD score ≤4 and at least a 2-point reduction from baseline and no subscore greater than 1 in any individual component; cClinical remission is defined as CDAI score <150; dDeep remission is defined as the composite of clinical remission and endoscopic remission. W, week; GUS, guselkumab; IV, intravenous; SC, subcutaneous; q8w, every 8 weeks; q4w, every 4 weeks; AE, adverse event; CD, Crohn’s disease; CDAI, Crohn’s Disease Activity Index; COVID-19, coronavirus disease 2019; SES-CD, Simple Endoscopic Score for Crohn’s Disease.
ir-2025-00150f5.jpg
ir-2025-00150f6.jpg
Table 1.
Baseline Demographic and Disease Characteristics in GALAXI 2 and 3 (East Asian Subpopulation)
Variable Placeboa (n=32) GUS 200 mg IV →100 mg SC q8w (n=63) GUS 200 mg IV →200 mg SC q4w (n=51) Ustekinumabb (n=46) Total (n=192)
Sex
 Male 24 (75.0) 36 (57.1) 38 (74.5) 36 (78.3) 134 (69.8)
 Female 8 (25.0) 27 (42.9) 13 (25.5) 10 (21.7) 58 (30.2)
Age (yr) 31.6±9.3 31.9±11.9 33.6±12.8 37.0±14.1 33.5±12.4
Weight (kg) 55.8±9.5 58.7±14.1 57.5±12.4 59.1±12.6 58.0±12.6
Duration of CD (yr) 6.1±4.8 6.0±5.4 5.9±6.9 6.6±7.0 6.2±6.1
CDAI
 Score 285.5±52.0 287.2±56.9 293.2±51.3 291.7±51.0 289.6±52.9
 Stool frequency count >3 19 (59.4) 38 (60.3) 30 (58.8) 26 (56.5) 113 (58.9)
 Abdominal pain score >1 28 (87.5) 60 (95.2) 46 (90.2) 41 (89.1) 175 (91.1)
SES-CD score 16.3±7.4 13.6±7.1 14.9±8.1 14.0±6.2 14.5±7.2
Endoscopic disease severity per SES-CD score
 <7 2 (6.3) 7 (11.1) 10 (19.6) 4 (8.7) 23 (12.0)
 7–16 16 (50.0) 34 (54.0) 19 (37.3) 28 (60.9) 97 (50.5)
 >16 14 (43.8) 22 (34.9) 22 (43.1) 14 (30.4) 72 (37.5)
Involved GI areas (assessed by central reader)
 Ileum only 3 (9.4) 4 (6.3) 11 (21.6) 4 (8.7) 22 (11.5)
 Colon only 16 (50.0) 23 (36.5) 18 (35.3) 17 (37.0) 74 (38.5)
 Ileum and colon 13 (40.6) 36 (57.1) 22 (43.1) 25 (54.3) 96 (50.0)
≥1 open or draining fistula 5 (15.6) 9 (14.3) 5 (9.8) 2 (4.3) 21 (10.9)
CRP (mg/L) 18.5±29.9 15.0±19.1 22.9±27.3 16.3±22.0 18.0±24.1
Fecal calprotectin (μg/g) 3,185±3,266 1,958±1,807c 2,315±1,821 2,402±2,133d 2,365±2,216e
Naive to biologic therapyf 3 (9.4) 13 (20.6) 12 (23.5) 8 (17.4) 36 (18.8)
History of intolerance or inadequate response to previous biologic therapyf 25 (78.1) 45 (71.4) 35 (68.6) 37 (80.4) 142 (74.0)

Values are presented as number (%) or mean±standard deviation.

a Placebo includes all participants randomized to placebo. At week 12, participants who were clinical responders continued placebo treatment and those who were non-responders received ustekinumab rescue therapy.

b Participants randomly allocated to ustekinumab.

c (n=62).

d (n=45).

e (n=190).

f Biological therapies include infliximab, adalimumab, certolizumab pegol, or vedolizumab (and approved biosimilars). Participants who had previously received a biological therapy targeting interleukin (IL)-12 or IL-23 were ineligible, except for those with minimal exposure to ustekinumab and no history of intolerance or inadequate response.

GUS, guselkumab; IV, intravenous; SC, subcutaneous; q8w, every 8 weeks; q4w, every 4 weeks; CD, Crohn’s disease; CDAI, Crohn’s Disease Activity Index; SES-CD, Simple Endoscopic Score for Crohn’s Disease; GI, gastrointestinal; CRP, C-reactive protein.

Table 2.
Summary of Short-Term Efficacy Endpoints Evaluating GUS 200 mg IV Induction at Week 12 in GALAXI 2 and 3 (East Asian Subpopulation and Global Population)a
Week 12 outcomeb East Asian, No. (%)
 Global, No (%)
GUS 200 mg IV combinedc (n=114) Placebo (n=32) GUS 200 mg IV combinedc (n=582) Placebo (n=148)
Clinical remissiond 53 (46.5) 4 (12.5) 274 (47.1) 28 (18.9)
Fatigue responsee 43 (37.7) 3 (9.4) 258 (44.3) 35 (23.6)
Endoscopic responsef 40 (35.1) 3 (9.4) 215 (36.9) 18 (12.2)
Clinical remission and endoscopic responsed,f 24 (21.1) 1 (3.1) 126 (21.6) 5 (3.4)

a Data for global participants have been reported previously [12].

b Participants who had a CD-related surgery, had a prohibited change in concomitant CD medication, discontinued study agent due to lack of efficacy or an adverse event of worsening CD, or discontinued study agent for any other reason other than COVID-19-related reasons or regional crisis prior to the analysis timepoint were considered not to have met the endpoint criteria. Participants who had discontinued study agent due to COVID-19-related reasons (excluding COVID-19 infection) or regional crisis had their observed data used, if available, to determine responder and nonresponder status at week 12. After accounting for these cases, those who were missing endpoint data at week 12 were considered not having achieved the endpoint at week 12.

c Participants assigned to either GUS group; at the week 12 assessment, GUS participants had received only GUS 200 mg IV.

d Clinical remission is defined as CDAI score <150.

e Fatigue response is defined as improvement of ≥7 points in PROMIS Fatigue Short Form 7a.

f Endoscopic response is defined as ≥50% improvement from baseline in SES-CD score or SES-CD score ≤2.

GUS, guselkumab; IV, intravenous; CD, Crohn’s disease; COVID-19, coronavirus disease 2019; CDAI, Crohn’s Disease Activity Index; PROMIS, Patient-Reported Outcomes Measurement Information System; SES-CD, Simplified Endoscopic Activity Score for Crohn’s Disease.

Table 3.
Summary of TEAEs through Week 48 in GALAXI 2 and 3 (East Asian Subpopulation and Global Population)a
Variable East Asian subpopulation
 Global population
PBO
 GUS 200 mg IV
 UST (n=46) PBO
 GUS 200 mg IV
 UST (n=291)
Onlyb (n=32) A-Rc (n=32) →100 mg SC q8w (n=63) →200 mg SC q4w (n=51) Onlyb (n=148) A-Rc (n=148) →100 mg SC q8w (n=286) →200 mg SC q4w (n=296)
Mean duration of follow-up (wk) 18.2 41.6 47.7 45.3 45.5 21.4 44.3 46.2 46.6 45.4
Total py follow-up 11.2 25.5 57.6 44.3 40.1 60.8 125.6 253.0 264.6 253.0
Participants with ≥1 TEAE 23 (71.9) 29 (90.6) 55 (87.3) 46 (90.2) 41 (89.1) 79 (53.4) 109 (73.6) 219 (76.6) 230 (77.7) 229 (78.7)
 TEAEs/100 py 779.6 548.5 390.7 444.5 316.5 478.9 350.3 321.4 354.2 345.8
Participants with ≥1 serious TEAE 5 (15.6) 6 (18.8) 7 (11.1) 4 (7.8) 6 (13.0) 16 (10.8) 23 (15.5) 30 (10.5) 21 (7.1) 34 (11.7)
 Serious TEAEs/100 py 71.7 39.2 15.6 13.5 19.9 34.6 24.7 14.2 9.8 18.6
Deaths 0 0 0 0 0 0 0 0 0 0
Participants with TEAEs leading to discontinuation of study agent 3 (9.4) 4 (12.5) 3 (4.8) 6 (11.8) 2 (4.3) 13 (8.8) 17 (11.5) 20 (7.0) 19 (6.4) 22 (7.6)
 TEAEs leading to discontinuation/100 py 26.9 15.7 5.2 15.8 7.5 21.4 13.5 8.3 7.6 9.1
Participants with ≥1 infectiond 8 (25.0) 15 (46.9) 36 (57.1) 28 (54.9) 24 (52.2) 37 (25.0) 61 (41.2) 122 (42.7) 146 (49.3) 122 (41.9)
Participants with ≥1 serious infectiond 2 (6.3) 4 (12.5) 0 0 2 (4.3) 2 (1.4) 6 (4.1) 1 (0.3) 3 (1.0) 11 (3.8)

Values are presented as number (%) unless otherwise indicated. Primary safety analysis set. Participants are counted only once for any given event under specific column, regardless of the number of times they actually experienced the event. Adverse events are coded using MedDRA (Medical Dictionary for Regulatory Activities) version 26.0. Participants randomized to GUS who received an incorrect treatment of UST are included in their randomized treatment columns.

a Data for global participants in the all-treated analysis population have been reported previously [12].

b Events in this column are attributed to those participants randomized to PBO with 1 exception: in the case where a participant is randomized to PBO and crosses over to UST, events occurring after receiving UST are not counted in this column.

c This includes all events in the randomized PBO group regardless of crossover to UST at or after week 12.

d Infections are based on MedDRA system organ class “Infections and Infestations.”

TEAEs, treatment-emergent adverse events; PBO, placebo; A-R, as-randomized; GUS, guselkumab; IV, intravenous; SC, subcutaneous; q8w, every 8 weeks; q4w, every 4 weeks; UST, ustekinumab; py, participant-year.

  • 1. Cushing K, Higgins PDR. Management of Crohn disease: a review. JAMA 2021;325:69–80.ArticlePubMedPMC
  • 2. Torres J, Mehandru S, Colombel JF, Peyrin-Biroulet L. Crohn’s disease. Lancet 2017;389:1741–1755.ArticlePubMed
  • 3. Kaplan GG, Windsor JW. The four epidemiological stages in the global evolution of inflammatory bowel disease. Nat Rev Gastroenterol Hepatol 2021;18:56–66.ArticlePubMedPDF
  • 4. Ng SC, Shi HY, Hamidi N, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet 2017;390:2769–2778.ArticlePubMed
  • 5. Mak WY, Zhao M, Ng SC, Burisch J. The epidemiology of inflammatory bowel disease: East meets West. J Gastroenterol Hepatol 2020;35:380–389.ArticlePubMedPDF
  • 6. Park SH. Update on the epidemiology of inflammatory bowel disease in Asia: where are we now? Intest Res 2022;20:159–164.ArticlePubMedPMCPDF
  • 7. Song EM, Yang SK. Natural history of inflammatory bowel disease: a comparison between the East and the West. Intest Res 2022;20:418–430.ArticlePubMedPDF
  • 8. Prideaux L, Kamm MA, De Cruz PP, Chan FK, Ng SC. Inflammatory bowel disease in Asia: a systematic review. J Gastroenterol Hepatol 2012;27:1266–1280.ArticlePubMed
  • 9. Ran Z, Wu K, Matsuoka K, et al. Asian Organization for Crohn’s and Colitis and Asia Pacific Association of Gastroenterology practice recommendations for medical management and monitoring of inflammatory bowel disease in Asia. J Gastroenterol Hepatol 2021;36:637–645.ArticlePubMedPDF
  • 10. Sachen KL, Hammaker D, Sarabia I, et al. Guselkumab binding to CD64+ IL-23-producing myeloid cells enhances potency for neutralizing IL-23 signaling. Front Immunol 2025;16:1532852.PubMedPMC
  • 11. Danese S, Panaccione R, Feagan BG, et al. Efficacy and safety of 48 weeks of guselkumab for patients with Crohn’s disease: maintenance results from the phase 2, randomised, double-blind GALAXI-1 trial. Lancet Gastroenterol Hepatol 2024;9:133–146.PubMed
  • 12. Panaccione R, Feagan BG, Afzali A, et al. Efficacy and safety of intravenous induction and subcutaneous maintenance therapy with guselkumab for patients with Crohn’s disease (GALAXI-2 and GALAXI-3): 48-week results from two phase 3, randomised, placebo and active comparator-controlled, double-blind, triple-dummy trials. Lancet 2025;406:358–375.PubMed
  • 13. Jun YK, Koh SJ, Myung DS, et al. Infectious complications in patients with inflammatory bowel disease in Asia: the results of a multinational web-based survey in the 8th Asian Organization for Crohn’s and Colitis meeting. Intest Res 2023;21:353–362.ArticlePubMedPMCPDF
  • 14. Park DI, Hisamatsu T, Chen M, et al. Asian Organization for Crohn’s and Colitis and Asia Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 1: risk assessment. Intest Res 2018;16:4–16.ArticlePubMedPMCPDF
  • 15. Ferrante M, Panaccione R, Baert F, et al. Risankizumab as maintenance therapy for moderately to severely active Crohn’s disease: results from the multicentre, randomised, double-blind, placebo-controlled, withdrawal phase 3 FORTIFY maintenance trial. Lancet 2022;399:2031–2046.ArticlePubMed
  • 16. Jairath V, Sands BE, Bossuyt P, et al. OP35 Efficacy of mirikizumab in comparison to ustekinumab in patients with moderate to severe Crohn’s disease: results from the phase 3 VIVID 1 study. J Crohns 2024;18:i62–64.ArticlePDF
  • 17. Loftus EV, Panés J, Lacerda AP, et al. Upadacitinib induction and maintenance therapy for Crohn’s disease. N Engl J Med 2023;388:1966–1980.ArticlePubMed

Figure & Data

REFERENCES

    Citations

    Citations to this article as recorded by  

      • PubReader PubReader
      • ePub LinkePub Link
      • Cite
        CITE
        export Copy Download
        Close
        Download Citation
        Download a citation file in RIS format that can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Reference Manager.
        Format:
        • RIS — For EndNote, ProCite, RefWorks, and most other reference management software
        • BibTeX — For JabRef, BibDesk, and other BibTeX-specific software
        Include:
        • Citation for the content below
        Guselkumab efficacy and safety in East Asian participants with moderately to severely active Crohn’s disease: subgroup analysis of the phase 3 GALAXI 2 and GALAXI 3 trials
        Close
      • XML DownloadXML Download
      Figure
      • 0
      • 1
      • 2
      • 3
      • 4
      • 5
      Related articles
      Guselkumab efficacy and safety in East Asian participants with moderately to severely active Crohn’s disease: subgroup analysis of the phase 3 GALAXI 2 and GALAXI 3 trials
      Image Image Image Image Image Image
      Fig. 1. Overview of GALAXI 2 and 3 trial design. aBiologic therapies: tumor necrosis factor antagonists or vedolizumab. To maintain treatment masking, all participants received active and/or placebo IV q4w through week 12 and active or placebo SC q4w through week 48. CDAI, Crohn’s Disease Activity Index; SF, stool frequency; AP, abdominal pain; SES-CD, Simple Endoscopic Score for Crohn’s Disease; 6-MP, 6-mercaptopurine; AZA, azathioprine; MTX, methotrexate; GUS, guselkumab; IV, intravenous; q4w, every 4 weeks; q8w, every 8 weeks; SC, subcutaneous; UST, ustekinumab.
      Fig. 2. Participant disposition in GALAXI 2 and 3 for the East Asian subpopulation. aParticipants who did not receive a maintenance dose and those who received placebo SC during the maintenance period; bParticipants who were not in clinical response to placebo induction dosing and crossed over to UST at W12 and continued to receive UST SC dosing in the maintenance period. GUS, guselkumab; IV, intravenous; SC, subcutaneous; q8w, every 8 weeks; q4w, every 4 weeks; UST, ustekinumab; W, week.
      Fig. 3. Proportions of participants achieving the composite primary (A, B) and major secondary (C, D) endpoints assessing short-term (W12) and long-term (W48) efficacy of guselkumab in the GALAXI 2 and 3 trials (East Asian subpopulation and global population).a Handling of missing data: participants who had a CD-related surgery; had a prohibited change in concomitant CD medication (including placebo participants in clinical response who crossover to ustekinumab at W12); discontinued study agent due to lack of efficacy, an AE of worsening CD, or W20/24 nonresponder; or discontinued study agent for any other reason other than COVID-19-related reasons or regional crisis prior to the analysis timepoint were considered not to have met the endpoint criteria. Participants who had discontinued study agent due to COVID-19-related reasons (excluding COVID-19 infection) or regional crisis had their observed data used, if available, to determine responder and nonresponder status at W12 and W48. After accounting for the above, participants who were missing CDAI score at W12 or CDAI or SES-CD score at W48 were considered not to have achieved the relevant endpoint. aData for global participants have been reported previously [12]; bClinical response is defined as ≥100-point reduction from baseline in CDAI score or CDAI score <150; cClinical remission is defined as CDAI score <150; dEndoscopic response is defined as ≥50% improvement from baseline in SES-CD score or SES-CD score ≤2; eCorticosteroid-free clinical remission is defined as clinical remission with no receipt of corticosteroids for 90 days before indicated timepoint; fEndoscopic remission (global definition) is defined as SES-CD score ≤4 and at least a 2-point reduction from baseline and no subscore greater than 1 in any individual component. W, week; GUS, guselkumab; IV, intravenous; SC, subcutaneous; q8w, every 8 weeks; q4w, every 4 weeks; CD, Crohn’s disease; AE, adverse event; COVID-19, coronavirus disease 2019; CDAI, Crohn’s Disease Activity Index; SES-CD, Simple Endoscopic Score for Crohn’s Disease.
      Fig. 4. Plots of change from baseline in CDAI scores (A), clinical remission rates (B) and PRO-2 remission rates (C) through W48 in GALAXI 2 and 3 (East Asian subpopulation). Handling of missing data: Participants who had a CD-related surgery, a prohibited change in concomitant CD medication, or discontinued study agent due to lack of efficacy, an AE of worsening CD, or W20/24 nonresponder or discontinued study agent for any other reason other than COVID-19-related reasons or regional crisis prior to the analysis timepoint were considered not to have met the endpoint criteria. Participants who had discontinued study agent due to COVID-19-related reasons (excluding COVID-19 infection) or regional crisis had their observed data used, if available, to determine responder and nonresponder status from that timepoint onwards. After accounting for the above, participants who were missing relevant scores at the designated analysis time-point were considered not to have achieved the endpoint at that timepoint. Clinical remission is defined as CDAI score <150. PRO-2 remission is defined as AP mean daily score at or below 1 and SF mean daily score at or below 3, and no worsening of AP or SF from baseline. CDAI, Crohn’s Disease Activity Index; GUS, guselkumab; IV, intravenous; SC, subcutaneous; q8w, every 8 weeks; q4w, every 4 weeks; PRO-2, patient-reported outcome-2; W, week; CD, Crohn’s disease; AE, adverse event; COVID-19, coronavirus disease 2019; AP, abdominal pain; SF, stool frequency.
      Fig. 5. Summary of proportions of participants achieving endoscopic response (A), endoscopic remission (B), the composite of clinical remission and endoscopic response (C), and deep remission (D) at W48 in GALAXI 2 and 3 (East Asian subpopulation and global population). Data for global participants have been reported previously [12]. Handling of missing data: Participants who had a CD-related surgery, a prohibited change in concomitant CD medication, or discontinued study agent due to lack of efficacy, an AE of worsening CD, or W20/24 nonresponder or discontinued study agent for any other reason other than COVID-19-related reasons or regional crisis prior to the analysis timepoint were considered not to have met the endpoint criteria. Participants who had discontinued study agent due to COVID-19-related reasons (excluding COVID-19 infection) or regional crisis had their observed data used, if available. After accounting for the above, participants who were missing endpoint data at the indicated timepoint were considered not to have achieved the relevant endpoint. aEndoscopic response is defined as ≥50% improvement from baseline in SES-CD score or SES-CD score ≤2; bEndoscopic remission (global definition) is defined as SES-CD score ≤4 and at least a 2-point reduction from baseline and no subscore greater than 1 in any individual component; cClinical remission is defined as CDAI score <150; dDeep remission is defined as the composite of clinical remission and endoscopic remission. W, week; GUS, guselkumab; IV, intravenous; SC, subcutaneous; q8w, every 8 weeks; q4w, every 4 weeks; AE, adverse event; CD, Crohn’s disease; CDAI, Crohn’s Disease Activity Index; COVID-19, coronavirus disease 2019; SES-CD, Simple Endoscopic Score for Crohn’s Disease.
      Graphical abstract

      Fig. 1.

      Fig. 2.

      Fig. 3.

      Fig. 4.

      Fig. 5.

      Graphical abstract

      Guselkumab efficacy and safety in East Asian participants with moderately to severely active Crohn’s disease: subgroup analysis of the phase 3 GALAXI 2 and GALAXI 3 trials
      Variable Placeboa (n=32) GUS 200 mg IV →100 mg SC q8w (n=63) GUS 200 mg IV →200 mg SC q4w (n=51) Ustekinumabb (n=46) Total (n=192)
      Sex
       Male 24 (75.0) 36 (57.1) 38 (74.5) 36 (78.3) 134 (69.8)
       Female 8 (25.0) 27 (42.9) 13 (25.5) 10 (21.7) 58 (30.2)
      Age (yr) 31.6±9.3 31.9±11.9 33.6±12.8 37.0±14.1 33.5±12.4
      Weight (kg) 55.8±9.5 58.7±14.1 57.5±12.4 59.1±12.6 58.0±12.6
      Duration of CD (yr) 6.1±4.8 6.0±5.4 5.9±6.9 6.6±7.0 6.2±6.1
      CDAI
       Score 285.5±52.0 287.2±56.9 293.2±51.3 291.7±51.0 289.6±52.9
       Stool frequency count >3 19 (59.4) 38 (60.3) 30 (58.8) 26 (56.5) 113 (58.9)
       Abdominal pain score >1 28 (87.5) 60 (95.2) 46 (90.2) 41 (89.1) 175 (91.1)
      SES-CD score 16.3±7.4 13.6±7.1 14.9±8.1 14.0±6.2 14.5±7.2
      Endoscopic disease severity per SES-CD score
       <7 2 (6.3) 7 (11.1) 10 (19.6) 4 (8.7) 23 (12.0)
       7–16 16 (50.0) 34 (54.0) 19 (37.3) 28 (60.9) 97 (50.5)
       >16 14 (43.8) 22 (34.9) 22 (43.1) 14 (30.4) 72 (37.5)
      Involved GI areas (assessed by central reader)
       Ileum only 3 (9.4) 4 (6.3) 11 (21.6) 4 (8.7) 22 (11.5)
       Colon only 16 (50.0) 23 (36.5) 18 (35.3) 17 (37.0) 74 (38.5)
       Ileum and colon 13 (40.6) 36 (57.1) 22 (43.1) 25 (54.3) 96 (50.0)
      ≥1 open or draining fistula 5 (15.6) 9 (14.3) 5 (9.8) 2 (4.3) 21 (10.9)
      CRP (mg/L) 18.5±29.9 15.0±19.1 22.9±27.3 16.3±22.0 18.0±24.1
      Fecal calprotectin (μg/g) 3,185±3,266 1,958±1,807c 2,315±1,821 2,402±2,133d 2,365±2,216e
      Naive to biologic therapyf 3 (9.4) 13 (20.6) 12 (23.5) 8 (17.4) 36 (18.8)
      History of intolerance or inadequate response to previous biologic therapyf 25 (78.1) 45 (71.4) 35 (68.6) 37 (80.4) 142 (74.0)
      Week 12 outcomeb East Asian, No. (%)
      		 Global, No (%)
      GUS 200 mg IV combinedc (n=114) Placebo (n=32) GUS 200 mg IV combinedc (n=582) Placebo (n=148)
      Clinical remissiond 53 (46.5) 4 (12.5) 274 (47.1) 28 (18.9)
      Fatigue responsee 43 (37.7) 3 (9.4) 258 (44.3) 35 (23.6)
      Endoscopic responsef 40 (35.1) 3 (9.4) 215 (36.9) 18 (12.2)
      Clinical remission and endoscopic responsed,f 24 (21.1) 1 (3.1) 126 (21.6) 5 (3.4)
      Variable East Asian subpopulation
      		 Global population
      PBO
      		 GUS 200 mg IV
      		 UST (n=46) PBO
      		 GUS 200 mg IV
      		 UST (n=291)
      Onlyb (n=32) A-Rc (n=32) →100 mg SC q8w (n=63) →200 mg SC q4w (n=51) Onlyb (n=148) A-Rc (n=148) →100 mg SC q8w (n=286) →200 mg SC q4w (n=296)
      Mean duration of follow-up (wk) 18.2 41.6 47.7 45.3 45.5 21.4 44.3 46.2 46.6 45.4
      Total py follow-up 11.2 25.5 57.6 44.3 40.1 60.8 125.6 253.0 264.6 253.0
      Participants with ≥1 TEAE 23 (71.9) 29 (90.6) 55 (87.3) 46 (90.2) 41 (89.1) 79 (53.4) 109 (73.6) 219 (76.6) 230 (77.7) 229 (78.7)
       TEAEs/100 py 779.6 548.5 390.7 444.5 316.5 478.9 350.3 321.4 354.2 345.8
      Participants with ≥1 serious TEAE 5 (15.6) 6 (18.8) 7 (11.1) 4 (7.8) 6 (13.0) 16 (10.8) 23 (15.5) 30 (10.5) 21 (7.1) 34 (11.7)
       Serious TEAEs/100 py 71.7 39.2 15.6 13.5 19.9 34.6 24.7 14.2 9.8 18.6
      Deaths 0 0 0 0 0 0 0 0 0 0
      Participants with TEAEs leading to discontinuation of study agent 3 (9.4) 4 (12.5) 3 (4.8) 6 (11.8) 2 (4.3) 13 (8.8) 17 (11.5) 20 (7.0) 19 (6.4) 22 (7.6)
       TEAEs leading to discontinuation/100 py 26.9 15.7 5.2 15.8 7.5 21.4 13.5 8.3 7.6 9.1
      Participants with ≥1 infectiond 8 (25.0) 15 (46.9) 36 (57.1) 28 (54.9) 24 (52.2) 37 (25.0) 61 (41.2) 122 (42.7) 146 (49.3) 122 (41.9)
      Participants with ≥1 serious infectiond 2 (6.3) 4 (12.5) 0 0 2 (4.3) 2 (1.4) 6 (4.1) 1 (0.3) 3 (1.0) 11 (3.8)
      Table 1. Baseline Demographic and Disease Characteristics in GALAXI 2 and 3 (East Asian Subpopulation)

      Values are presented as number (%) or mean±standard deviation.

      Placebo includes all participants randomized to placebo. At week 12, participants who were clinical responders continued placebo treatment and those who were non-responders received ustekinumab rescue therapy.

      Participants randomly allocated to ustekinumab.

      (n=62).

      (n=45).

      (n=190).

      Biological therapies include infliximab, adalimumab, certolizumab pegol, or vedolizumab (and approved biosimilars). Participants who had previously received a biological therapy targeting interleukin (IL)-12 or IL-23 were ineligible, except for those with minimal exposure to ustekinumab and no history of intolerance or inadequate response.

      GUS, guselkumab; IV, intravenous; SC, subcutaneous; q8w, every 8 weeks; q4w, every 4 weeks; CD, Crohn’s disease; CDAI, Crohn’s Disease Activity Index; SES-CD, Simple Endoscopic Score for Crohn’s Disease; GI, gastrointestinal; CRP, C-reactive protein.

      Table 2. Summary of Short-Term Efficacy Endpoints Evaluating GUS 200 mg IV Induction at Week 12 in GALAXI 2 and 3 (East Asian Subpopulation and Global Population)a

      Data for global participants have been reported previously [12].

      Participants who had a CD-related surgery, had a prohibited change in concomitant CD medication, discontinued study agent due to lack of efficacy or an adverse event of worsening CD, or discontinued study agent for any other reason other than COVID-19-related reasons or regional crisis prior to the analysis timepoint were considered not to have met the endpoint criteria. Participants who had discontinued study agent due to COVID-19-related reasons (excluding COVID-19 infection) or regional crisis had their observed data used, if available, to determine responder and nonresponder status at week 12. After accounting for these cases, those who were missing endpoint data at week 12 were considered not having achieved the endpoint at week 12.

      Participants assigned to either GUS group; at the week 12 assessment, GUS participants had received only GUS 200 mg IV.

      Clinical remission is defined as CDAI score <150.

      Fatigue response is defined as improvement of ≥7 points in PROMIS Fatigue Short Form 7a.

      Endoscopic response is defined as ≥50% improvement from baseline in SES-CD score or SES-CD score ≤2.

      GUS, guselkumab; IV, intravenous; CD, Crohn’s disease; COVID-19, coronavirus disease 2019; CDAI, Crohn’s Disease Activity Index; PROMIS, Patient-Reported Outcomes Measurement Information System; SES-CD, Simplified Endoscopic Activity Score for Crohn’s Disease.

      Table 3. Summary of TEAEs through Week 48 in GALAXI 2 and 3 (East Asian Subpopulation and Global Population)a

      Values are presented as number (%) unless otherwise indicated. Primary safety analysis set. Participants are counted only once for any given event under specific column, regardless of the number of times they actually experienced the event. Adverse events are coded using MedDRA (Medical Dictionary for Regulatory Activities) version 26.0. Participants randomized to GUS who received an incorrect treatment of UST are included in their randomized treatment columns.

      Data for global participants in the all-treated analysis population have been reported previously [12].

      Events in this column are attributed to those participants randomized to PBO with 1 exception: in the case where a participant is randomized to PBO and crosses over to UST, events occurring after receiving UST are not counted in this column.

      This includes all events in the randomized PBO group regardless of crossover to UST at or after week 12.

      Infections are based on MedDRA system organ class “Infections and Infestations.”

      TEAEs, treatment-emergent adverse events; PBO, placebo; A-R, as-randomized; GUS, guselkumab; IV, intravenous; SC, subcutaneous; q8w, every 8 weeks; q4w, every 4 weeks; UST, ustekinumab; py, participant-year.

      Table 1.

      Table 2.

      Table 3.

      Intest Res : Intestinal Research
      © Korean Association for the Study of Intestinal Diseases.
      Close layer
      TOP