Introduction

Guselkumab (GUS) intravenous (IV) induction followed by subcutaneous (SC) maintenance with 200mg q4w or 100mg q8w was effective in the GALAXI 2 & 3 phase 3 treat-through studies of participants (pts) with moderately to severely active Crohn’s disease (CD), with similar efficacy between both maintenance doses in the overall study populations. Here, we evaluated the efficacy of maintenance doses in subgroups by baseline disease activity and severity and inflammatory burden at Week (Wk) 12 to determine if some pts may receive additional benefit from the higher maintenance dose.

Aims & Methods

Eligible pts had moderately to severely active CD (CDAI 220–450 and mean daily stool frequency score >3 or abdominal pain score >1), SES-CD ≥6 (≥4 for isolated ileal disease), and inadequate response or intolerance to oral corticosteroids, AZA, 6-MP, MTX, or biologics. Pts were randomly assigned to GUS 200mg IV at Wks 0, 4, and 8, followed by GUS SC 100mg q8w (N=286) or 200mg q4w (N=296). The studies also included placebo and ustekinumab arms, but this analysis focused on differences between GUS maintenance doses. Wk48 endpoints included clinical remission (CDAI <150) and endoscopic response (≥50% improvement in SES-CD or SES-CD ≤2). Analyses of subgroups by baseline disease activity (CDAI >300 or SES-CD >12), and inflammatory burden (CRP >5) or endoscopic response at Wk 12 were prespecified but not multiplicity controlled.

Results

In the pooled GALAXI 2 & 3 dataset, pts with baseline high disease activity (CDAI >300 or SES-CD >12) had numerically greater clinical and endoscopic outcomes at Wk 48 with 200mg q4w compared with 100mg q8w. Pts with baseline CDAI >300 had numerically greater percentages of clinical remission (200mg: 68.0% [83/122] vs 100mg: 55.1% [65/118], respectively) and endoscopic response (52.5% [64/122] vs 44.1% [52/118]) at Wk 48. Pts with baseline SES-CD >12 also had numerically greater percentages of these outcomes (clinical remission: 77.0% [94/122] vs 65.1% [82/126] and endoscopic response 67.2% [82/122] vs 58.7% [74/126]). Pts with baseline CDAI ≤300 or SES-CD ≤12 had similar Wk 48 outcomes for both maintenance doses. Pts with greater inflammatory burden (CRP >5mg/L) at Wk 12 or who were not in endoscopic response at Wk 12 also had numerically greater clinical and endoscopic outcomes at Wk 48 with 200mg compared with 100mg (Table). Pts with CRP ≤5mg/L or who were in endoscopic response at Wk 12 had similar clinical and endoscopic outcomes for both maintenance doses. Results for individual GALAXI 2 & 3 studies generally trended in the same direction for all subgroups.

Table. Week 48 Outcomes by CRP and Endoscopic Response Status at Week 12
Week 48 outcome by status at Week 12	Guselkumab 200 mg q4w (N=278)	Guselkumab 100 mg q8w (N=268)
CRP>5mg/L at Week 12	107/278 (38.5%)	85/268 (31.7%)
Clinical remission at Week 48	76/107 (71.0%)	46/85 (54.1%)
Endoscopic response at Week 48	54/107 (50.5%)	31/85 (36.5%)
Not in endoscopic response at Week 12	177/278 (63.7%)	156/268 (58.2%)
Clinical remission at Week 48	120/177 (67.8%)	97/156 (62.2%)
Endoscopic response at Week 48	79/177 (44.6%)	50/156 (32.1%)
Clinical remission was defined as CDAI score <150; endoscopic response was defined as ≥50% improvement from baseline in SES-CD or SES-CD ≤2

Conclusion

Pts with high clinical or endoscopic disease severity at baseline, greater inflammatory burden after induction, or who had not achieved endoscopic response after induction showed greater clinical and endoscopic outcomes at Wk 48 with GUS 200mg SC q4w compared with 100mg SC q8w.

Disclosure

AA: AbbVie, Bristol Myers Squibb/Celgene, DiaSorin, Eli Lilly, Gilead, IBD Horizons, Johnson & Johnson, Pfizer, Takeda, and TLL Pharmaceuticals
TH: grants 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, Abivax, Bristol Myers Squibb, EA Pharma Co. Ltd., Gilead Sciences, Janssen Pharmaceutical K.K., Lilly, Mitsubishi Tanabe Pharma Corporation, and Pfizer Inc.; 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.
DTR: consulting/speaker fees/advisory board 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; membership on Board of Directors of Cornerstones Health, Inc and Crohn’s & Colitis Foundation’s Board of Trustees.
NAT, RVR, JY, KYYW, and ZY: employees of and may own Johnson & Johnson stock.
WR: speaker for AbbVie, Celltrion, Ferring, Johnson & Johnson, Galapagos Medice, MSD, Roche, Pfizer, Sobi, Takeda; consultant for AbbVie, Amgen, AOP Orphan, Boehringer Ingelheim, Bristol Myers Squibb, Calyx, Celltrion, Eli Lilly, Galapagos, Gilead, Index Pharma, Johnson & Johnson, Medahead, Microbiotica, Pfizer, Takeda; advisory board member for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Galapagos, Johnson & Johnson, Pfizer; funding from AbbVie, Johnson & Johnson, Sandoz, Sanofi, Takeda.
BES: consulting fees from AbbVie, Adiso Therapeutics, Agomab, Alimentiv, Amgen, AnaptysBio, Arena Pharmaceuticals, AstraZeneca, Biolojic Design, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Celltrion, Equillium, Enthera, Enveda Biosciences, Evommune, Ferring, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Imhotex, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Kaleido, Kallyope, Merck, Microba, Mirador Therapeutics, 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, Sorriso Pharmaceuticals, Spyre Therapeutics, Sun Pharma, Surrozen, Target RWE, Teva, TLL Pharmaceutical, Tr1X, Union Therapeutics, Ventyx Biosciences, and Vividion Therapeutics; consulting /speaking fees from Abivax; consulting/speaking fees/other support from Lilly; research grants/consulting/speaking fees/other support from Bristol Myers Squibb, Johnson & Johnson, Pfizer, and Takeda; stock/options from Ventyx Biopharma.
SD: consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, AstraZeneca, Athos, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Enthera, Ferring, Gilead, Hospira, Inotrem, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity, Takeda, TiGenix, UCB, and Vifor; lecture fees from AbbVie, Amgen, Ferring, Gilead, Janssen, Mylan, Pfizer, and Takeda.
RP: consulting fees from Abbivax, Abbott, AbbVie, Alimentiv, Amgen, AnaptsyBio, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, JAMP Bio, Johnson & Johnson, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Spyre Therapeutics, Sublimity Therapeutics, Takeda Pharmaceuticals, Theravance Biopharma, Trellus, Union Biopharma, Viatris, Ventyx, and UCB; speaker’s fees from AbbVie, Amgen, Arena Pharmaceuticals, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Gilead Sciences, Johnson & Johnson, Merck, Organon, Pfizer, Roche, Sandoz, Shire, and Takeda Pharmaceuticals; Advisory Boards for AbbVie, Alimentiv, Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Johnson & Johnson, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Shire, Sublimity Therapeutics, Takeda Pharmaceuticals, and Ventyx.

Introduction

Postoperative recurrence (POR) after ileocecal resection for Crohn's disease (CD) represents a significant clinical challenge

Aims & Methods

This study aimed to identify clinical risk factors for surgical recurrence in patients undergoing ileocecal resection for CD. This multicenter retrospective cohort study included 1,066 patients with CD who underwent ileocecal resection across 13 Italian centers. Univariate and multivariate logistic regression analyses were performed to identify clinical risk factors associated with surgical recurrence.

Results

The cohort comprised 59.0% males with a median age at diagnosis of 29 years [IQR: 22-40]. Most patients presented with stricturing disease (55.2%) or penetrating disease (40.9%), with ileal (49.6%) and ileocolonic (47.6%) locations predominating. Over a median follow-up of 70 months [IQR: 31-131], 101 patients (9.5%) required recurrent surgery. The median time to recurrent surgery was 78.5 months [IQR: 19.0-138.0]. Most patients (72.3%) had at least one clinical risk factor for POR, with penetrating phenotype (40.4%), previous intestinal resections (27.2%), and perianal disease (21.4%) being most common.
Univariate analysis identified significant risk factors for surgical recurrence including prior intestinal resection (OR 5.56, 95% CI 3.62-8.56, p<0.001), perianal disease (OR 3.50, 95% CI 2.28-5.35, p<0.001), large intestinal resection ≥50 cm (OR 4.80, 95% CI 3.04-7.58, p<0.001), and continued smoking after surgery (OR 1.84, 95% CI 1.16-2.94, p=0.010). Disease duration >10 years (OR 2.20, 95% CI 1.44-3.36, p<0.001) and colonic involvement (L2: OR 3.00, 95% CI 1.18-7.65, p=0.021) increased risk, while ileal localization (L1) was protective (OR 0.35, 95% CI 0.22-0.54, p<0.001). Bowel perforation as surgical indication significantly increased recurrence risk (OR 2.58, 95% CI 1.29-5.16, p=0.007). Multivariate analysis confirmed perianal disease (aOR 2.58, 95% CI 1.56-4.26, p<0.001), previous intestinal resection (aOR 5.70, 95% CI 3.52-9.23, p<0.001), and large resection (aOR 4.04, 95% CI 2.43-6.72, p<0.001) as independent predictors of recurrence. Unlike previous studies, penetrating behavior was not associated with increased risk, while disease duration >10 years and colonic involvement emerged as significant factors. Additionally, this study uniquely identified bowel perforation as a surgical indication distinct from other penetrating complications in predicting recurrence.

Table 1: Independent Risk Factors for Surgical Recurrence After Ileocecal Resection in Crohn's Disease

Risk Factor	Odds Ratio (95% CI)	p-value
Previous intestinal resection	5.70 (3.52-9.23)	<0.001
Large intestinal resection (≥50 cm)	4.04 (2.43-6.72)	<0.001
Perianal disease	2.58 (1.56-4.26)	<0.001
Continued smoking after surgery	2.23 (1.30-3.83)	0.004
Bowel perforation as surgical indication	2.58 (1.29-5.16)	0.007
Disease duration >10 years	2.20 (1.44-3.36)	<0.001
Ileal localization (L1)	0.35 (0.22-0.54)	<0.001

Conclusion

This large cohort study identified several robust predictors of surgical recurrence after ileocecal resection for CD, with some notable differences from prior research. Previous intestinal resection, perianal disease, large intestinal resection, colonic involvement, and continued smoking emerged as particularly strong risk factors, while penetrating disease behavior was not confirmed as a predictor. These findings challenge some aspects of current risk stratification guidelines and can help inform personalized postoperative management strategies.

Introduction

Mirikizumab (MIRI), a p19-directed antibody against interleukin-23, demonstrated improvements in fatigue, abdominal pain (AP) and stool frequency (SF) at Week (W) 12 and W52 in the VIVID-1 clinical trial.¹

Aims & Methods

The aim of this analysis is to show the effect of MIRI on fatigue, AP, SF and achievement of clinical remission by Patient-Reported Outcome (PRO; SF ≤3 and AP ≤1 and neither worse than baseline) in the VIVID-2 open-label extension study through W104. This analysis includes data from primary analysis set in patients with Crohn’s disease (CD) randomised to the MIRI treatment arm in VIVID-1 who achieved endoscopic response (≥50% reduction from baseline in Simple endoscopic score for CD) at W52 and continued the MIRI subcutaneous dosing (300 mg) in VIVID-2. Change from VIVID-1 baseline was measured for continuous endpoints. Endpoints included fatigue measured using FACIT-Fatigue (measured as change from baseline, and clinically-meaningful improvement of ≥6-points among patients with baseline ≤46), AP improvement (measured as change from baseline, and achievement of ≤1 among patients with baseline >1), SF improvement (measured as change from baseline, and achievement of ≤3 among patients with baseline >3) and clinical remission by PRO, assessed at W64 and 104. Missing data were handled using observed case (OC) and modified non-responder imputation (mNRI) for response rates, while using modified baseline observation carried forward (mBOCF) for change from baseline. Response rates were presented as unadjusted proportions with 2-sided 95% confidence intervals using the Rubin's Rules (mNRI). ANCOVA models were used for continuous variables, adjusting for baseline values and intervention group.

Results

Fatigue mean (standard error [SE]) change from baseline was 10.7 (0.56) at W64; 9.4 (0.59) at W104, (observed response, n [%]: 152 [67.6%] at W64; 136 [64.8%] at W104; Table). AP improved (mean [SE] change: −1.5 [0.04] at W64; −1.6 [0.05] at W104), with response rates increasing from 174 (77.3%) to 161 (84.7%). SF showed sustained improvement (mean [SE] change: −4.3 [0.14] at W64; −4.3 [0.16] at W104), with response rates reaching 155 (89.6%) at W104 (Table). Similar rates of achievement of clinical remission by PRO were observed (178 [73.6%] at W64; 165 [80.1%] at W104) (Table).

Table: Improvement in fatigue, abdominal pain, stool frequency and achievement of clinical remission by PRO up to Week 104

	FACIT-Fatigue (N=251)		Abdominal pain (N=251)		Stool frequency (N=251)		Clinical remission by PRO (N=251)
	Week 64	Week 104	Week 64	Week 104	Week 64	Week 104	Week 64	Week 104
Change from baselinea (mBOCF), LSM (SE)	10.7 (0.56)	9.4 (0.59)	−1.5 (0.04)	−1.6 (0.05)	−4.3 (0.14)	−4.3 (0.16)	NA	NA
Response (observed)b, n (%) (95% CI)	152 (67.6) (61.2–73.3)	136 (64.8) (58.1–70.9)	174 (77.3) (71.4–82.3)	161 (84.7) (78.9–89.2)	175 (86.6) (81.3–90.6)	155 (89.6) (84.2–93.3)	178 (73.6) (67.7–78.7)	165 (80.1) (74.1–85.0)
Responseb (mNRI), % (95% CI)	67.1 (61.0–73.3)	60.8 (54.4–67.2)	76.7 (71.2–82.2)	79.2 (73.7–84.7)	85.8 (80.9–90.6)	84.0 (78.8–89.2)	72.6 (66.9–78.2)	75.0 (69.4–80.7)

CI, confidence interval; LSM, least squares mean; mBOCF, modified baseline observation carried forward; mNRI, modified non-responder imputation; n, no of patients; NA, not applicable; PRO, Patient-Reported Outcome; SE, standard error
^aBaseline of VIVID-1 study
^bFACIT-Fatigue: ≥6-point improvement for baseline score ≤46; Abdominal pain: achievement of ≤1 for baseline score >1; Stool frequency: achievement of ≤3 for baseline score >3; Clinical remission by PRO: SF ≤3 and AP ≤1 and neither worse than baseline

Conclusion

MIRI sustained improvement in fatigue, AP, SF and clinical remission by PRO through 104 weeks of continuous treatment. These consistent findings support the long-term treatment with MIRI to address key symptoms of CD.

References

1. Ferrante, MarcTron, Emiliano, et al. The Lancet. 404 (10470):2423-2436.

Disclosure

PB: Received financial support for research from AbbVie, EG; lecture fees from AbbVie, AMC ICP, Amgen, Bristol Myers Squibb, Celltrion, Dr Falk Benelux, EG, Galapagos, Globalport, Lilly, Medtalks, Materia Prima, Pentax, Springer Media; served on an advisory board for AbbVie, Bristol Meyers Squibb, CIRC, Galapagos, Janssen, Lilly, Pentax, PSI-CRO, Roche, Takeda, Tetrameros. AA: Consultant for Geneoscopy; received research support from Takeda. AV, GY and JW: Employee and shareholder of Eli Lilly and Company. NL: Consultant for Eli Lilly and Company. JRA: Consultant for Janssen, Pfizer, Abbvie, Vedanta, Geneteche, Seres Therapeutics, Ferring, GSK, Merck, Bristol Myer Squibb, Roivant, Celltrion, and TRXBio, Xencor, Shattuck Labs; Speaker for Abbvie, Janssen. MC: Provided educational activities for AbbVie, China Medical System, IPSEN, Janssen, and Takeda; served on an advisory board for Boehringer Ingelheim and Janssen; and has support for clinical research from Janssen and Takeda.

Introduction

Despite the benefits of available therapies for Crohn’s disease (CD), many patients (pts) lose treatment response over time, highlighting the need for options with sustained effectiveness.^1-3 Part 2 of the SEQUENCE trial is an open-label extension (OLE) study that evaluates the long-term efficacy and safety of the interleukin-23 p19 inhibitor risankizumab (RZB) in pts with moderate to severe CD and prior anti-TNF failure. Here, we evaluated the durability of clinical remission, quality of life (QoL), and inflammatory biomarker outcomes in RZB-treated pts through week (wk) 100 of SEQUENCE.

Aims & Methods

In SEQUENCE (NCT04524611), pts randomised to the RZB arm during Part 1 who completed the wk48 visit continued to receive open-label 360mg subcutaneous RZB maintenance dose every 8 wks starting at wk52 (baseline of Part 2).⁴ We assessed the proportion of pts achieving clinical remission (per CD activity index [CDAI] and stool frequency/abdominal pain score [SF/APS]) and Inflammatory Bowel Disease Questionnaire (IBDQ) remission at wks 8, 24, 52, 76, and 100. Additionally, pts with elevated high-sensitivity C-reactive protein (hs-CRP; > 5 mg/L) or faecal calprotectin (FCP; > 250 µg/g) at baseline were assessed for normalization of hs-CRP or FCP at wks 8, 24, 52, 76, and 100. We also assessed the proportion of pts who achieved these endpoints at wk100 among pts who also achieved that endpoint previously at either wk8 or at wk52. Data were assessed for all intent-to-treat pts using As Observed (AO) and per Non Responder imputation (NRI). Safety was not assessed in this post hoc analysis, although previously reported.⁵

Results

Of the 224 pts who entered SEQUENCE Part 2, the proportion of pts who achieved clinical remission (per AO data) increased from wk8 to wk52, and remained stable up to wk100 (CDAI: 48.0% [n/N=96/200] at wk8, 75.3% [168/223] at wk52, and 84.4% [141/167] at wk100; SF/APS: 44.0% [88/200] at wk8, 71.2% [158/222] at wk52, and 74.7% [124/166] at wk100) (Table). Similar trends were observed (per AO data) for IBDQ remission (41.5% [88/212] at wk8, 62.1% [139/224] at wk52, and 65.3% [126/193] at wk100), normalisation of hs-CRP (38.8% [54/139] at wk8, 53.1% [76/143] at wk52, and 62.0% [80/129] at wk100), and normalisation of FCP (34.6% [46/133] at wk8, 56.9% [87/153] at wk52, and 60.0% [75/125] at wk100). Most pts who achieved clinical remission at wk8 remained in remission at wk100, and the same was observed for patients in remission at both wk52 and wk100 (AO data; respectively, CDAI: 96.1% [73/76] and 91.1% [123/135]; SF/APS: 90.1% [64/71] and 86.8% [112/129]). A durable effect was also observed from wk8 to wk100 and from wk52 to wk100 in the majority of RZB-treated pts across all other endpoints (AO data; respectively, IBDQ remission: 91.5% [65/71] and 85.7% [102/119]); normalisation of hs-CRP: 80.0% [40/50] and 81.2% [56/69]; normalisation of FCP: 81.1% [30/37] and 85.1% [57/67]). Similar results to AO data were observed per NRI data (Table).

Endpoint, n/N (%) [95% CI]a	AOb	NRIc
CDAI clinical remissiond Week 8 Week 24 Week 52e Week 76 Week 100 Week 100 among pts who achieved at Week 8 Week 100 among pts who achieved at Week 52 SF/APS clinical remissionf Week 8 Week 24 Week 52e Week 76 Week 100 Week 100 among pts who achieved at Week 8 Week 100 among pts who achieved at Week 52 IBDQ remissiong Week 8 Week 24 Week 52e Week 76 Week 100 Week 100 among pts who achieved at Week 8 Week 100 among pts who achieved at Week 52 Normalisation of hs-CRPh Week 8 Week 24 Week 52e Week 76 Week 100 Week 100 among pts who achieved at Week 8 Week 100 among pts who achieved at Week 52 Normalisation of FCPi Week 8 Week 24 Week 52e Week 76 Week 100 Week 100 among pts who achieved at Week 8 Week 100 among pts who achieved at Week 52	96/200 (48.0) [41.1, 54.9] 148/199 (74.4) [68.3, 80.4] 168/223 (75.3) [69.7, 81.0] 140/168 (83.3) [77.7, 89.0] 141/167 (84.4) [78.9, 89.9] 73/76 (96.1) [91.7, 100.0] 123/135 (91.1) [86.3, 95.9] 88/200 (44.0) [37.1, 50.9] 135/198 (68.2) [61.7, 74.7] 158/222 (71.2) [65.2, 77.1] 125/167 (74.9) [68.3, 81.4] 124/166 (74.7) [68.1, 81.3] 64/71 (90.1) [83.2, 97.1] 112/129 (86.8) [81.0, 92.7] 88/212 (41.5) [34.9, 48.1] 129/212 (60.8) [54.3, 67.4] 139/224 (62.1) [55.7, 68.4] 135/201 (67.2) [60.7, 73.7] 126/193 (65.3) [58.6, 72.0] 65/71 (91.5) [85.1, 98.0] 102/119 (85.7) [79.4, 92.0] 54/139 (38.8) [30.7, 47.0] 68/139 (48.9) [40.6, 57.2] 76/143 (53.1) [45.0, 61.3] 82/139 (59.0) [50.8, 67.2] 80/129 (62.0) [53.6, 70.4] 40/50 (80.0) [68.9, 91.1] 56/69 (81.2) [71.9, 90.4] 46/133 (34.6) [26.5, 42.7] 64/129 (49.6) [41.0, 58.2] 87/153 (56.9) [49.0, 64.7] 71/130 (54.6) [46.1, 63.2] 75/125 (60.0) [51.4, 68.6] 30/37 (81.1) [68.5, 93.7] 57/67 (85.1) [76.5, 93.6]	94/224 (42.0) [35.5, 48.4] 145/224 (64.7) [58.5, 71.0] 168/224 (75.0) [69.3, 80.7] 136/224 (60.7) [54.3, 67.1] 134/224 (59.8) [53.4, 66.2] 70/94 (74.5) [65.7, 83.3] 117/168 (69.6) [62.7, 76.6] 88/224 (39.3) [32.9, 45.7] 133/224 (59.4) [52.9, 65.8] 158/224 (70.5) [64.6, 76.5] 121/224 (54.0) [47.5, 60.5] 117/224 (52.2) [45.7, 58.8] 61/88 (69.3) [59.7, 79.0] 107/158 (67.7) [60.4, 75.0] 86/224 (38.4) [32.0, 44.8] 126/224 (56.3) [49.8, 62.7] 139/224 (62.1) [55.7, 68.4] 133/224 (59.4) [52.9, 65.8] 122/224 (54.5) [47.9, 61.0] 62/86 (72.1) [62.6, 81.6] 99/139 (71.2) [63.7, 78.7] 54/143 (37.8) [29.8, 45.7] 67/143 (46.9) [38.7, 55.0] 76/143 (53.1) [45.0, 61.3] 80/143 (55.9) [47.8, 64.1] 77/143 (53.8) [45.7, 62.0] 40/54 (74.1) [62.4, 85.8] 53/76 (69.7) [59.4, 80.1] 46/153 (30.1) [22.8, 37.3] 64/153 (41.8) [34.0, 49.6] 87/153 (56.9) [49.0, 64.7] 71/153 (46.4) [38.5, 54.3] 73/153 (47.7) [39.8, 55.6] 29/46 (63.0) [49.1, 77.0] 56/87 (64.4) [54.3, 74.4]
Table. Achievement of Endpoints Over Time and at Week 100 in Patients Who Achieved Endpoints at Weeks 8 and 52. Abbreviations: AO, as observed, CDAI, Crohn’s Disease Activity Index; FCP, faecal calprotectin; hs-CRP; high-sensitivity C-reactive protein; IBDQ; Inflammatory Bowel Disease Questionnaire; NRI, nonresponder imputation; OLE, open-label extension; pt, patient; SF/APS, stool frequency/abdominal pain score. The study population includes all intent-to-treat patients who received at least one dose of study drug in the SEQUENCE OLE. aConstruction of CIs for response rate is based on the normal approximation to the binomial distribution. bFor the AO analysis, data were used as is; 16 patients received at least one dose of rescue therapy during Part 2. cOnly patients with 2-year matured data or those who discontinued the study early are included in the NRI analysis. Pts were categorised as non-responders for visits with missing assessments, visits after premature discontinuation of study, and visits after initiation of rescue therapy (if applicable). dCDAI clinical remission: CDAI < 150. eValues for wk52 represent the most recent non-missing assessment prior to the start of Part 2. fSF/APS clinical remission: Average daily SF ≤ 2.8 and not worse than baseline value and average daily APS ≤ 1 and not worse than baseline value. gIBDQ remission is defined as IBDQ total score ≥ 170 points. hC-reactive protein (hs-CRP) ≤ 5 mg/L. iFCP ≤ 250 µg/g.

Conclusion

Pts with moderately to severely active CD receiving RZB demonstrated durable clinical remission, IBDQ remission, and inflammatory biomarker reductions through wk100 in the SEQUENCE OLE. Notably, most pts who achieved efficacy endpoints early maintained effectiveness during continued RZB treatment.

References

1. Colombel JF, et al. Gastroenterology. 2007;132:52–65.
2. Hanauer SB, et al. Lancet. 2002;359:1541–9.
3. Turner D, et al. Gastroenterology. 2021;160:1570–83.
4. Peyrin-Biroulet L, et al. N Engl J Med. 2024;391:213–23.

Disclosure

Raja Atreya has served as a speaker, or consultant, or received research grants from AbbVie, Abivax, AlfaSigma, AstraZeneca, Bristol Myers Squibb, CED Service, Celltrion Healthcare, Dr Falk, Galapagos, Johnson & Johnson, Eli Lilly, MSD Sharp & Dohme, Pfizer, Takeda Pharma.
James O. Lindsay has served as a consultant and an advisory board participant for AbbVie, Astra Zeneca, Bristol Myers Squibb, , Celltrion, Eli Lilly, Engytix, Ferring Pharmaceuticals, Galapagos, Gilead, GSK, Janssen, MSD, Pfizer, Takeda, and Vifor Pharma; has received speaker fees and sponsorship for academic meetings from AbbVie, Ferring Pharmaceuticals, Janssen, MSD, Pfizer, Tillotts Pharma, and Takeda; and has received investigator-led research grants from AbbVie, Gilead, Pfizer, and Takeda.
Marc Ferrante has received research grants from AbbVie, EG Pharma, Janssen, Pfizer, Takeda, and Viatris; consultancy fees from AbbVie, AgomAb Therapeutics, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Janssen-Cilag, Merck Sharp and Dohme, MRM Health, Pfizer, Takeda, and ThermoFisher; and speakers’ fees from AbbVie, Biogen, Boehringer Ingelheim, Dr Falk Pharma, Ferring, Janssen-Cilag, Merck Sharp and Dohme, Pfizer, Takeda, Truvion Healthcare, and Viatris.
Britta Siegmund has received consulting fees from AbbVie, Abivax, Boehringer Ingelheim, BMS, Dr Falk, Endpoint Health, Galapagos, Gilead, Janssen, Landos, Lilly, Pfizer, and Takeda, and speaker’s fees from AbbVie, AlfaSigma, BMS, CED Service, Dr Falk, Ferring, Galapagos, Janssen, Lilly, MSD, Pfizer, and Takeda.
Qian Cao has served as a steering committee adviser for Bristol Myers Squibb Company, and Janssen Research Development, LLC; and has received research grants from Takeda and Johnson & Johnson.
Stijn van Haaren, Jameson Crowley, Toni Anschutz, and Andrew Garrison are full-time employees of AbbVie and may own AbbVie stock or stock options.
Marla Dubinsky has received consulting and advisory fees from AbbVie, Abivax, Astra Zeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Eli Lilly, Genentech, Gilead, GSK, Janssen, Johnson and Johnson, Merck, Pfizer, Prometheus Labs, Prometheus Biosciences, Sanofi, Spyre and Takeda
Funding: AbbVie funded this trial and participated in the trial design, research, analysis, data collection, interpretation of data, and the review and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. AbbVie and the authors thank the patients, study sites, and investigators who participated in this clinical trial. Medical writing support was provided by Mahesh Chemudupati, PhD of AbbVie. Editorial support was provided by Amy Kuang, PhD of AbbVie.