Introduction
The comparable efficacy and safety of both IV and SC induction with guselkumab (GUS), a dual-acting IL-23p19 subunit inhibitor, in pts with moderately to severely active CD has been established in the phase 3 GALAXI and GRAVITI studies.1,2,3 To determine whether pts with higher baseline disease severity respond differently to IV or SC induction, we compared the efficacy of GUS IV and SC induction in subgroups based on baseline disease characteristics.
Aims & Methods
Pts had moderately to severely active CD (CDAI 220-450 and SES-CD≥6 or if ileal disease only, SES-CD≥4), and a history of inadequate response/intolerance to oral corticosteroids, AZA/6-MP/MTX, or biologics. GUS induction regimen was 200mg IV q4w in GALAXI 2 & 3 (N=582) and 400mg SC q4w in GRAVITI (N=230), while matching IV/SC PBO q4w (N=148 and N=117, respectively) was the comparator regimen. Clinical remission (CDAI<150) and endoscopic response (≥50% improvement from baseline SES-CD) were evaluated at Wk12 for predefined subgroups based on baseline involved disease location, CDAI, SES-CD, C-reactive protein (CRP), and fecal calprotectin (FeCal). Abnormal CRP was defined as >3 mg/L and >5 mg/L for GALAXI and GRAVITI, respectively.
Results
GALAXI and GRAVITI had similar entry criteria, and baseline disease characteristics of the randomized study populations were also similar. Pts treated with IV or SC GUS induction achieved clinical remission at Wk12 in greater proportions than those who received PBO across subgroups of disease location (ileal only [IV: GUS=44%, PBO=13%; SC: GUS=56%, PBO=27%], colon only [IV: GUS=44% vs PBO=18%; SC: GUS=56% vs PBO=18%], and both ileum and colon [IV: GUS=52% vs PBO=24%; SC: GUS=57% vs PBO=22%]), baseline CDAI (≤300 [IV: GUS=52%, PBO=25%; SC: GUS=66%, PBO=26%] and >300 [IV: GUS=40% vs PBO=10%; SC: GUS=41% vs PBO=14%]), baseline SES-CD (≤12 [IV: GUS=43%, PBO=21%; SC: GUS=52%, PBO=24%] and >12 [IV: GUS=53% vs PBO=16%; SC: GUS=62% vs PBO=18%]), baseline CRP (≤3mg/L or ≤5mg/L in GALAXI and GRAVITI, respectively, [IV: GUS=45%, PBO=17%; SC: GUS=53%, PBO=28%] and >3mg/L or >5mg/L [IV: GUS=48% vs PBO=20%; SC: GUS=59% vs PBO=17%]), and baseline FeCal (≤250μg/g [IV: GUS=49%, PBO=25%; SC: GUS=60%, PBO=26%] and >250μg/g [IV: GUS=46% vs PBO=16%; SC: GUS=54% vs PBO=20%]). Endoscopic response at Wk12 was also achieved by greater proportions of GUS- than PBO-induced pts across all subgroups with either IV or SC induction (Table).
Table. Endoscopic Response at Week 12 by Baseline Disease Characteristics
| IV Induction (GALAXI 2&3)
| SC Induction (GRAVITI)
|
| Placebo IV
| GUS 200 mg IV
| Δ (95% CI); p-value
| Placebo SC
| GUS 400 mg SC
| Δ (95% CI); p-value
|
Full analysis set, N (%)
| 148 (12.2%)
| 582 (36.9%)
| 25.2 (18.8, 31.6); Nominal P<0.001
| 117 (21.4%)
| 230 (41.3%)
| 19.9 (10.2, 29.6); P<0.001
|
Involved disease location,a n/N (%)
Ileum only
Colon only
Ileum and colon
|
1/31 (3.2%)
10/62 (16.1%)
7/55 (12.7%)
|
28/139 (20.1%)
89/225 (39.6%)
98/218 (45.0%)
|
18.4 (8.8, 28.0)*
19.7 (8.9, 30.6)*
33.1 (22.1, 44.1)*
|
1/22 (4.5%)
7/40 (17.5%)
17/55 (30.9%)
|
14/52 (26.9%)
35/81 (43.2%)
46/97 (47.4%)
|
23.0 (8.6, 37.3)*
25.4 (8.9, 42.0)*
15.0 (-0.9, 30.8)
|
CDAI score, n/N (%)
≤300
>300
|
12/89 (13.5%)
6/59 (10.2%)
|
131/342 (38.3%)
84/240 (35.0%)
|
25.5 (17.1, 34.0)*
25.3 (15.7, 34.9)*
|
18/68 (26.5%)
7/49 (14.3%)
|
60/137 (43.8%)
35/93 (37.6%)
|
18.1 (4.8, 31.4)*
22.4 (8.5, 36.4)*
|
SES-CD score, n/N (%)
≤12
>12
|
8/84 (9.5%)
10/64 (15.6%)
|
104/334 (31.1%)
111/248 (44.8%)
|
21.9 (14.0, 29.8)*
29.4 (18.9, 39.9)*
|
15/72 (20.8%)
10/45 (22.2%)
|
49/140 (35.0%)
46/90 (51.1%)
|
14.0 (1.7, 26.3)*
29.1 (13.6, 44.6)*
|
C-reactive protein (mg/L),b n/N (%)
≤3
>3
≤5
>5
|
10/52 (19.2%)
8/96 (8.3%)
-
-
|
72/164 (43.9%)
143/418 (34.2%)
-
-
|
27.3 (14.5, 40.0)*
26.0 (18.8, 33.2)*
-
-
|
-
-
13/47 (27.7%)
12/70 (17.1%)
|
-
-
48/110 (43.6%)
47/120 (39.2%)
|
-
-
16.0 (0.5, 31.4)*
20.3 (7.9, 32.7)*
|
Fecal calprotectin (μg/g), n/N (%)
≤250
>250
|
4/36 (11.1%)
14/111 (12.6%)
|
45/108 (41.7%)
169/469 (36.0%)
|
26.7 (12.8, 40.6)*
23.8 (16.4, 31.3)*
|
9/31 (29.0%)
16/86 (18.6%)
|
29/67 (43.3%)
65/162 (40.1%)
|
14.0 (-7.4, 35.5)
20.9 (10.1, 31.8)*
|
*Nominal p-value for subgroup <0.05
CDAI=Crohn’s disease activity index; CI=confidence interval; IV=intravenous; SC= subcutaneous; SES-CD=simple endoscopic score for Crohn’s disease.
a Assessed by central reader. b Abnormal C-reactive protein was defined as >3mg/L in GALAXI and >5mg/L in GRAVITI.
Note: Endoscopic response was defined as a ≥50% improvement from baseline SES-CD (also defined as SES-CD≤2 in GALAXI). Participants who had a CD-related surgery (with the exception of minor procedures such as drainage of a superficial abscess or seton placement, etc.), a prohibited change in CD medication, or discontinued study intervention for any reason (other than COVID-19 related reasons [excluding COVID-19 infection] or regional crisis) were considered not to have met the endpoint at the designated timepoint. Participants who discontinued study intervention due to COVID-19 related reasons (excluding COVID-19 infection) or regional crisis had their observed data used, if available. After accounting for the aforementioned data handling rules, participants who were missing data pertaining to an endpoint at a designated timepoint were considered not to have achieved the endpoint. The adjusted treatment difference(s), confidence interval(s), and p-value(s) were based on the common risk difference by use of Mantel-Haenszel stratum weights and the Sato variance estimator. The stratification factors are baseline CDAI score (≤300 or >300), baseline SES-CD score (≤12 or >12), BIO-failure status at baseline (yes or no), and baseline corticosteroid use (yes or no; GALAXI only). |
Conclusion
Both IV and SC induction with GUS were similarly effective in pts with moderately to severely active CD across predefined subgroups of disease location and baseline clinical, endoscopic, and inflammatory biomarker disease activity. The treatment effects were consistent in the subgroups following IV and SC induction, particularly in those that represent high disease severity.
References
- Sachen K, Hammaker D, Sarabia I, et al. Frontiers in Immunology. 2025: doi:10.3389/fimmu.2025.1532852.
- Panaccione R, Danese S, Feagan BG, et al. Gastroenterology. 2024; 166(5): S1057b.
- Hart A, Panaccione R, Steinwurz F, et al. Gastroenterology. 2025: doi:10.1053/j.gastro.2025.02.033.
Disclosure
BES reports consulting fees from Abbvie, Adiso Therapeutics, Agomab, Alimentiv , Amgen, AnaptysBio, Arena Pharmaceuticals, Artugen Therapeutics, Astra Zeneca, Biolojic Design, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Calibr, Celgene, Celltrion, ClostraBio, Equillium, Enthera, Enveda Biosciences, Evommune, Ferring, Fresenius Kabi, Fzatat, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Imhotex, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Kaleido, Kallyope, Merck, Microba, Mobius Care, Morphic Therapeutics, MRM Health, Nexus Therapeutics, Nimbus Discovery, Odyssey Therapeutics, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Therapeutics, Reistone Biopharma, Sanofi, Spyre Therapeutics, Sun Pharma, Surrozen, Target RWE,Teva, TLL Pharmaceutical, Tr1X, Union Therapeutics, Ventyx Biosciences; consulting and speaking fees from Abivax; consulting and speaking fees and other support from Lilly; research grants, consulting and speaking fees and other support from Bristol Myers Squibb, Janssen, Pfizer, Takeda; research grants and consulting fees from Theravance Biopharma; and stock/stock options from Ventyx Biopharma.
TH received grant support from Mitsubishi Tanabe Pharma Corporation, EA pharma Co. Ltd., AbbVie GK, JIMRO Co. Ltd., Zeria Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd., Takeda Pharmaceutical Co. Ltd., Pfizer Inc., Mochida Pharmaceutical Co. Ltd., Boston Scientific Corporation, Kissei Pharmaceutical Co. Ltd., consulting fees from Mitsubishi Tanabe Pharma Corporation, EA pharma Co. Ltd., AbbVie GK, Janssen Pharmaceutical K.K., Pfizer Inc., Nichi-Iko Pharmaceutical Co. Ltd., Eli Lilly, Gilead Sciences, Bristol Myers Squibb, and lecture fee from Mitsubishi Tanabe Pharma Corporation, AbbVie GK, EA pharma Co. Ltd., Kyorin Pharmaceutical Co. Ltd., JIMRO Co., Janssen Pharmaceutical K.K., Mochida Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co. Ltd., Pfizer Inc. Kissei Pharmaceutical Co. Ltd.
AA reports potential conflicts of interest with AbbVie, Bristol Myers Squibb/Celgene, DiaSorin, Eli Lilly, Gilead, IBD Horizons, Janssen, Pfizer, Takeda, and TLL Pharmaceuticals.
NAT, MO, RVR, JY, and WvD are employees of Johnson & Johnson and own company stock/stock options.
AH served as a clinical investigator and consultant for Janssen.
SD reports consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, AstraZeneca, Athos, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Enthera, Ferring, Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity, Takeda, TiGenix, UCB and Vifor; and reports lecture fees from AbbVie, Amgen, Ferring, Gilead, Janssen, Mylan, Pfizer and Takeda.
RP reports having received consulting fees from Abbivax, Abbott, AbbVie, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring,Fresenius Kabi, Galapagos, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Takeda Pharmaceuticals, Theravance Biopharma, Trellus, Viatris, Ventyx, UCB; Speaker’s Fees from AbbVie, Amgen, Arena Pharmaceuticals, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Gilead Sciences, Janssen, Merck, Organon, Pfizer, Roche, Sandoz, Shire, Takeda Pharmaceuticals and served on Advisory Boards for: AbbVie, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Shire, Sublimity Therapeutics, Takeda Pharmaceuticals, and Ventyx.
