DOP001 Extraintestinal manifestations in participants with moderately to severely active Crohn’s disease: Results from the phase 3 GALAXI 2 & 3 studies

Abstract Background Extraintestinal manifestations (EIMs), including joint, skin, and ocular manifestations, are common in patients with IBD. The phase 3 GALAXI 2 & 3 studies evaluated guselkumab (GUS), a dual-acting IL-23p19 subunit inhibitor, in participants(pts) with moderately to severely active CD.1,2 Here, we present EIMs reported through week (Wk)48 in the pooled GALAXI 2/3 studies. Methods Pts were randomly assigned to GUS 200mg IV at Wks 0/4/8, then GUS SC 100mg q8w (N = 286) or 200mg q4w (N = 296), or placebo (PBO, N = 148). The studies also included ustekinumab (UST), but the current analyses do not include UST. Corticosteroids (CS) were maintained at baseline (BL) doses through Wk12, when mandatory tapering began. EIMs (arthritis/arthralgia, erythema nodosum/pyoderma gangrenosum, & iritis/uveitis) were reported as a component of the Crohn’s Disease Activity Index (CDAI) score at each visit along with individual EIM resolution and de novo EIMs at Wks12 & 48. EIM data were pooled for GALAXI 2/3. Results Overall, 34.5% (201/582) of GUS and 42.6% (63/148) of PBO-treated pts had EIMs at BL (Table). Among pts with EIMs at BL, arthritis/arthralgia was reported in 89.1% and 90.5% of GUS and PBO-treated pts, respectively. Erythema nodosum/pyoderma gangrenosum was reported in 18.4% and 25.4% of pts, respectively. Rates of iritis/uveitis were low, 5.5% and 3.2%, respectively, and were not evaluated due to small sample size. Overall, 14.4% (29/201) of GUS and 17.5% (11/63) of PBO-treated pts with EIMs were receiving prednisone at baseline. Fig 1A shows percentages of pts with EIMs at BL and Wk12. Greater proportions of GUS (59.2%) vs PBO-treated (42.9%) pts had resolution of their overall EIMs after induction (Wk12): arthritis/arthralgia (55.3% vs 33.3%) and erythema nodosum/pyoderma gangrenosum (75.7% vs 56.3%), respectively. Overall, rates of de novo EIMs at Wk12 were low, 2.6% and 8.1%, respectively. Greater improvements in weighted EIM CDAI component scores were reported from BL through Wk12 (LS Means [SE]: -5.4 [0.43]) in the GUS-treated pts (both doses combined) vs PBO (-0.70 [0.83]). At Wk48, the proportions of pts with arthritis/arthralgia or erythema nodosum/pyoderma gangrenosum decreased from BL in both GUS treatment groups (Fig 1B). LS Mean change [SE] from BL in weighted EIM CDAI component scores at Wk48 were similar between the GUS 100mg SC q8w (-5.5 [0.57]) and GUS 200mg SC q4w (-6.1 [0.57]) groups. Conclusion Pts treated with GUS vs PBO had greater EIM resolution at Wk12, and improvements continued to Wk48. Pts receiving GUS also had lower rates of de novo EIMs at Wk12 compared with PBO. These results suggest GUS may improve and prevent EIMs in pts with CD. References: 1.Panaccione R, Danese S, Feagan BG, et al. Gastroenterology 2024;166(5):S1057b. 2.Panaccione R, Feagan BG, Afzali A, et al. Lancet 2025;406(10501):358-375. Conflict of interest: Danese, Silvio: Personal Fees: AbbVie, Alimentiv, Allergan, Amgen, Applied Molecular Transport, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals Inc., Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB Inc., Vial, Vifor Lecture fees from Abbvie, Amgen, Ferring Pharmaceuticals Inc., Gilead, Janssen, Mylan, Pfizer, Takeda Hisamatsu, Tadakazu: Grant support: Mitsubishi Tanabe Pharma Corporation, EA pharma Co. Ltd., AbbVie GK, JIMRO Co. Ltd., Zeria Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., Pfizer Inc., Mochida Pharmaceutical Co. Ltd., Boston Scientific Corporation, Kissei Pharmaceutical Co. Ltd. Consulting: Mitsubishi Tanabe Pharma Corporation, EA pharma Co. Ltd., AbbVie GK, Janssen Pharmaceutical K.K., Pfizer Inc., Eli Lilly, Gilead Sciences, Bristol Myers Squibb, Abivax, MSD, Chugai. Lecture fee: 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. Van Rampelbergh, Rian: Employee of Johnson & Johnson and may own company stock/stock options. Van Duijnhoven, Wilbert: Employee of Johnson & Johnson (and stock holder) Scapini, Gustavo: Employee of Johnson & Johnson and owns stock/stock options. Adsul, Shashi: Current employee of Johnson & Johnson past Employee of Takeda Pharmaceutical. Rubin, David T.: DTR reports consulting and/or speaker fees and/or advisory board participation for AbbVie, Altrubio, Apex, Avalo, Bristol Myers Squibb, Buhlmann Diagnostics, Celgene, Connect BioPharma, Intouch Group, Iterative Health, Johnson & Johnson, Lilly, Pfizer, Samsung Neurologica, and Takeda Altrubio, Datos Health, and Iterative Health stock options grants from Takeda and membership on the Board of Directors of Cornerstones Health, Inc and on the Crohn’s & Colitis Foundation’s Board of Trustees.