Introduction

The Phase 2 GALAXI 1 study evaluated the efficacy and safety of guselkumab (GUS), a human selective IL-23p19 subunit antagonist, in patients (pts) with moderate to severe Crohn’s disease (CD). Pts were randomized to GUS, ustekinumab (UST), or placebo (PBO) through Week (Wk) 48 without rerandomization after IV induction. Previously, we reported that pts who were in clinical response after IV induction had higher rates of clinical and endoscopic outcomes at Wk48 than the overall study population.¹ In this post hoc analysis, we report outcomes for pts who did not achieve Wk12 clinical response based on CD activity index (CDAI) after IV induction.

Aims & Methods

Pts were randomized 1:1:1:1:1 to induction with GUS 200, 600, or 1200mg IV, UST ~6mg/kg IV, or PBO IV. At Wk12 (Wk8 for UST), pts were transitioned to maintenance dosing: GUS 200mg IV→100mg subcutaneous (SC) q8w, GUS 600mg IV→200mg SC q4w, GUS 1200mg IV→200mg SC q4w, UST ~6mg/kg IV→90mg SC q8w, PBO nonresponders→UST ~6mg/kg IV→90mg SC q8w, and PBO responders→PBO SC q4w. Clinical response (all time points) was defined as ≥100-point reduction from baseline in CDAI or CDAI <150. Other endpoints included clinical remission (CDAI <150), pt-reported outcome (PRO)-2 remission (unweighted CDAI components of average daily abdominal pain score ≤1 and average daily stool frequency ≤3, and no worsening from baseline), and endoscopic response (≥50% improvement from baseline in simple endoscopic score [SES]-CD or SES-CD ≤2). The study was not powered to evaluate between-group efficacy differences at Wk48; UST was used for reference.

Results

Table. Efficacy Outcomes Among Patients Not in Clinical Responsea at Week 12
Outcome, %b, c	Week	Combined Guselkumab (N=63)	Ustekinumab (N=21)
Clinical responsea	16 / 20 / 24	36.5 / 47.6 / 46.0	42.9 / 52.4 / 52.4
	28 / 32 / 36	47.6 / 54.0 / 50.8	42.9 / 47.6 / 57.1
	40 / 44	54.0 / 52.4	52.4 / 47.6
	48	58.7	47.6
Clinical remissiond	48	41.3	33.3
PRO-2 remissione	48	42.9	23.8
Endoscopic responsef	48	31.7	23.8
AP=abdominal pain; CD=Crohn’s disease; CDAI=Crohn’s disease activity index; PRO-2=Patient-reported CDAI components of abdominal pain and stool frequency; SES-CD=Simple Endoscopic Score for Crohn’s Disease; SF=stool frequency. a Clinical response was defined as ≥100-point reduction from baseline in CDAI or CDAI <150. b Patients who had a prohibited change in concomitant CD medication, a CD-related surgery, or discontinued study agent due to lack of efficacy, or an adverse event of worsening CD prior to the designated analysis timepoint, were considered not to have achieved the endpoint. c Patients who had insufficient data to calculate the outcome measure at the designated analysis timepoint were considered not to have achieved the endpoint. d Clinical remission was defined as a CDAI <150. e PRO-2 remission was defined as unweighted CDAI component of average daily AP pain score ≤1 and the unweighted CDAI component of average daily SF ≤3, and no worsening of AP or SF from baseline. f Endoscopic response was defined as ≥50% improvement from baseline in SES-CD or SES-CD ≤2.

At Wk12, 63/185 (34.1%) GUS pts and 21/63 (33.3%) UST did not achieve CDAI clinical response. Among GUS Wk12 nonresponders, 46.0% were in clinical response by Wk24 (Table). Percentages of Wk12 nonresponders who went on to achieve outcomes at Wk48 in the GUS and UST groups, respectively, were as follows: clinical response, 58.7% and 47.6%; clinical remission, 41.3% and 33.3%; PRO-2 remission, 42.9% and 23.8%; and endoscopic response, 31.7% and 23.8% (Table).

Conclusion

Pts not responding to IV induction with GUS may benefit from continued SC dosing. Among pts who did not achieve clinical response at Wk12, continued treatment with GUS SC resulted in nearly half achieving clinical response at Wk24. At Wk48, a majority achieved clinical response, >40% achieved either clinical remission or PRO-2 remission, and >30% achieved endoscopic response.

References

1. Panés J, et al. UEG Journal 2022; 10 (Suppl 8).

Disclosure

RP reports consulting fees, speaker fees, or research support from Abbott, AbbVie, Abbivax, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Fresenius Kabi, 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, and UCB.
AA reports consulting fees from AbbVie, Takeda, Janssen, Bristol Myers Squibb/Celgene, Pfizer, Eli Lilly, Gilead, DiaSorin, and TLL Pharmaceuticals; reports speaker fees from Abbvie, Takeda, Janssen, Bristol Myers Squibb, and Pfizer; has served on advisory boards for Abbvie, Takeda, Janssen, Bristol Myers Squibb, Pfizer, Eli Lilly, and Gilead; has received research/education support from AbbVie, Janssen, Pfizer, Bristol Myers Squibb, and Takeda; and is the co-founder of IBD Horizons.
GRDH served as advisor for Abbvie, Ablynx, Amakem, Amgen, AM Pharma, Avaxia, Biogen, Bristol Myers Squibb, Boehringer Ingelheim, Celgene/Receptos, Celltrion, Cosmo, Covidien/Medtronics, Ferring, DrFALK Pharma, Eli Lilly, Engene, Galapagos, Genentech/Roche, Gilead, Glaxo-Smith Kline, Immunic, Johnson and Johnson, Lycera, Medimetrics, Millenium/Takeda, Mitsubishi Pharma, Merck Sharp Dome, Mundipharma, Nextbiotics, Novonordisk, Otsuka, Pfizer/Hospira, Prometheus laboratories/Nestle, Protagonist, Robarts Clinical Trials, Salix, Samsung Bioepis, Sandoz, Setpoint, Shire, Teva, Tigenix, Tillotts, Topivert, Versant, and Vifor; and has received speaker fees from Abbvie, Biogen, Ferring, Johnson and Johnson, Merck Sharp Dome, Mundipharma, Norgine, Pfizer, Samsung Bioepis, Shire, Millenium/Takeda, Tillotts, and Vifor.
LS, NAT, AS, MEF, and ZY are employees of Janssen Research & Development, LLC and own stock/stock options.
EZ reports receiving research support and consulting fees from Janssen, AbbVie, Takeda, Neopharm, Celgene, and Pfizer.
SD reports receiving consulting fees from Allergan, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Celgene, Celltrion Healthcare, Ferring, Gilead Sciences, Hospira, Inc., Janssen Research & Development, LLC, Johnson & Johnson Health Care Systems, Inc., Pfizer, Sandoz, UCB, and Vifor International Inc.
TH has performed joint research with Alfresa Pharma Co. Ltd., and EA Pharma Co. Ltd.; has received grant support from Mitsubishi Tanabe Pharma Corporation, EA Pharma Co. Ltd., AbbVie GK, JIMRO Co. Ltd., Zeria Pharmaceutical Co. Ltd., Daiichi-Sankyo, Kyorin Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd., Takeda Pharmaceutical Co. Ltd., Pfizer Inc., Mochida Pharmaceutical Co. Ltd., and JIMRO Co. Ltd; has received consulting fees from EA Pharma Co. Ltd., AbbVie GK, Celgene K.K., Janssen Pharmaceutical K.K., Pfizer Inc., and Nichi-Iko Pharmaceutical Co., Ltd; and has received lecture fees 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., and Pfizer Inc.

Introduction

The concept of disease clearance (DC), which includes symptomatic, endoscopic and histologic remission, has been proposed as the ultimate goal in ulcerative colitis (UC) treatment. However, the prognostic value of this endpoint remains uncertain.¹ Etrasimod is an investigational, oral, once-daily, selective sphingosine 1‑phosphate (S1P)_1,4,5 receptor modulator in development for the treatment of moderately to severely active UC.

Aims & Methods

We report a post hoc analysis from the ELEVATE UC trials to assess relationships between histological/composite endpoints, biomarkers and efficacy outcomes in etrasimod-treated patients (pts). In ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369), pts with moderately to severely active UC were randomised 2:1 to once‑daily etrasimod 2 mg or placebo (PBO). DC was defined as Nancy Histological Index=0, Mayo endoscopic subscore [ES]=0, rectal bleeding subscore=0, stool frequency subscore=0 or 1 (if 1, must have ≥ 1 point decrease from baseline). Other endpoints are defined in the Table. Kappa correlation coefficients² were estimated between histological endpoints at Wk 12 and efficacy outcomes at Wk 52, and between histological endpoints and biomarkers at Wks 12 and 52.

Results

At Wk 12 in both trials, DC was achieved by more etrasimod- than PBO-treated pts (8.4% [23/274] vs 1.5% [2/135] and 9.9% [22/222] vs 4.5% [5/112], p<0.001 and p=0.042, respectively). The proportion of pts with clinical remission at Wk 52 was higher among pts who achieved DC at Wk 12 (17/23; 74%) vs pts who did not (71/251; 28%). Histologic-endoscopic mucosal improvement at Wk 12 had the highest correlation with efficacy outcomes at Wk 52 (κ 0.357–0.438; Table). Faecal calprotectin and C‑reactive protein normalisation showed slight/fair to substantial agreement with histologic endpoints (κ 0.223–0.630; 0.075–0.6, respectively; Table). Absolute lymphocyte count < 0.5x10⁹/L showed no agreement (κ -0.100–0.216; Table).

Table. Correlations between histological and efficacy endpoints in ELEVATE UC 52, and histological endpoints and biomarker status in ELEVATE UC 52 and 12 among patients (with baseline modified Mayo score of 5 to 9) receiving etrasimod 2 mg QD
Correlations with Wk 12 histological endpoints and efficacy endpoints at Wk 52 of ELEVATE UC 52
ELEVATE UC 52: Wk 12 endpoint (N=274)	Definition	Clinical remissiond at Wk 52		CS-free clinical remissione at Wk 52		Symptomatic remissionf at Wk 52	Endoscopic improvementg at Wk 52	Endoscopic improvement- histologic remissionh at Wk 52
Histologic remissiona Histologic-endoscopic mucosal improvementa Endoscopic improvement-histologic remissionb Endoscopic normalisation-histologic remissionc Disease clearancec	Geboes < 2.0 Geboes ≤ 3.1 + ES 0–1 Geboes < 2.0 + ES 0–1 Geboes < 2.0 + ES 0 NHI=0, ES=0, RBS=0, SFS=0 or 1 (if 1, must have ≥ 1-point decrease from baseline)	0.266 0.392 0.338 0.217 0.200		0.266 0.392 0.338 0.217 0.200		0.299 0.357 0.297 0.169 0.164	0.292 0.423 0.367 0.223 0.194	0.365 0.438 0.431 0.307 0.260
Correlations with biomarker status at the same visit (Wk 12 and Wk 52)
ELEVATE UC 12: Wk 12 endpoint (N=222) ELEVATE UC 52: Wk 12 or Wk 52 endpoints (N=274)	Absolute lymphocyte count (< 0.5 x 109/L)			Faecal calprotectin normalisation (< 150 mg/kg)			hsCRP normalisation (< 5 mg/L)
Histologic remissiona Histologic-endoscopic mucosal improvementa Endoscopic improvement-histologic remissionb Endoscopic normalisation-histologic remissionc Disease clearancec	ELEVATE UC 12 (Wk 12) 0.060 0.124 0.041 0.004 -0.022	ELEVATE UC 52 (Wk 12) -0.006 -0.100 -0.055 0.036 0.014	ELEVATE UC 52 (Wk 52) 0.216 0.132 0.160 0.098 0.067	ELEVATE UC 12 (Wk 12) 0.370 0.535 0.290 0.227 0.236	ELEVATE UC 52 (Wk 12) 0.268 0.497 0.298 0.257 0.223	ELEVATE UC 52 (Wk 52) 0.571 0.630 0.538 0.458 0.431	ELEVATE UC 12 (Wk 12) 0.199 0.180 0.386 0.075 0.084	ELEVATE UC 52 (W12) 0.193 0.267 0.287 0.089 0.094	ELEVATE UC 52 (Wk 52) 0.497 0.533 0.600 0.373 0.365
Kappa correlation coefficients are shown, ≤ 0 indicate no agreement, 0.01–0.20 indicate none to slight agreement, 0.21–0.40 indicate in fair agreement, 0.41–0.60 indicate in moderate agreement, 0.61–0.80 indicate substantial agreement, and coefficients 0.81–1.00 indicate an almost perfect agreement aPre-specified exploratory endpoint; bPre-specified key secondary endpoint subject to type I error control; cPost hoc endpoint; dClinical remission was defined as SFS=0 (or =1 with a ≥ 1-point decrease from baseline), RBS=0, and ES ≤ 1 (excluding friability); eCS-free clinical remission was defined as the proportion of patients in clinical remission at Wk 52 and who had not been receiving CS for ≥ 12 wks prior to Wk 52; fSymptomatic remission was defined as SFS=0 (or =1 with a ≥ 1-point decrease from baseline) and RBS=0; gEndoscopic improvement was defined as an ES ≤ 1 (excluding friability); hEndoscopic improvement-histologic remission was defined as ES ≤ 1 (excluding friability) with histologic remission measured by a Geboes Index score < 2.0 CS, corticosteroid; ES, endoscopic subscore; hsCRP, high-sensitivity C-reactive protein; NHI, Nancy Histological Index; RBS, rectal bleeding subscore; SFS, stool frequency subscore; QD, once daily; Wk, week

Conclusion

Early achievement of DC showed only fair correlation with Wk 52 efficacy outcomes. Correlation of faecal calprotectin < 150 mg/kg with histological endpoints was most often moderate and improved from Wks 12 to 52. A different approach is needed for development of robust predictive models.

References

1. D’Amico F et al. United Eur Gastroenterol J 2022;10:777–784
2. Cohen JA et al. Educ Psychol Meas 1960;20:37–46

Disclosure

FM: grant support: GEDII and National Science Foundation; personal fees: AbbVie, Amgen, Biogen, Celgene, Celltrion, Dr. Falk Pharma, Ferring Pharmaceuticals, Hospira, Janssen, Laboratórios Vitória, MSD, Pfizer, Sandoz, Takeda, UCB, Vifor.
LPB: grant/research support: Takeda, Fresenius Kabi and Celltrion; consultancy fees: AbbVie, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena Pharmaceuticals, Biogen, Bristol-Myers Squibb, Celltrion, CONNECT Biopharm, Cytoki Pharma, Enthera, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos, Genentech, Gilead Sciences, Gossamer Bio, GSK, HAC-Pharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Eli Lilly, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par'Immune, Pfizer Inc, Prometheus, Protagonist, Roche, Sandoz, Takeda, Theravance, Thermo Fisher, TiGenix, Tillotts, Viatris, Vifor, Ysopia and Abivax; lecture/speaker fees: Galapagos, AbbVie, Janssen, Genentech, Ferring Pharmaceuticals, Tillotts, Celltrion, Takeda, Pfizer, Sandoz, Biogen, MSD, Amgen, Vifor, Arena Pharmaceuticals, Eli Lilly, Gilead Sciences, Viatris, Medac, Sanofi; holds stock in CTMA.
BES: research grants: Arena, Janssen. Lecture fees/Speakers Bureau: Bristol-Myers Squibb, Janssen, Lilly, Pfizer, Takeda. Consultancy, Advisory Committee/Board Member: AbbVie, Alimentiv, Amgen, Arena, AstraZeneca, Boehringer-Ingelheim, Bristol Myers Squibb, Celltrion, Fresenius Kabi, Genentech, Glaxo SmithKline, Janssen, Lilly, Merck, Pfizer, Prometheus Biosciences, Sun Pharma Global, Takeda Pharmaceuticals International, Teva Branded Pharmaceutical Products R&D. Shareholder/Stock Options: Ventyx Biosciences. Other non-financial support: Janssen, Lilly, Pfizer, Takeda.
SD: consultancy/advisory fees: AbbVie, Allergan, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Ferring Pharmaceuticals, Gilead Sciences, Hospira, Janssen, Johnson & Johnson, MSD, Mundipharma, Pfizer Inc, Roche, Sandoz, Takeda, TiGenix, UCB and Vifor; lecture/speaker fees: AbbVie, Amgen, Ferring Pharmaceuticals, Gilead Sciences, Janssen, Mylan, Pfizer Inc, Takeda; has directorship/ownership interests in Gastroenterology and Endoscopy.
VJ: financial support: Celgene/Bristol-Myers Squibb, Pfizer, AbbVie, Boehringer Ingelheim, Eli Lilly, Janssen, Takeda, Gilead and TiGenix; consultancy: AbbVie, Alimentiv, Amgen, Anokion, Applied Strategic, Arena, Asahi Kasei, Asieris, AstraZeneca, BIOJAMP, Celgene/Bristol-Myers Squibb, Celltrion, Eli Lilly, Ferring, F Hoffmann La Roche, Flagship Pioneering, Fresenius Kabi, Fusion MD, Galapagos, Genentech, Gilead, GSK, Janssen, Knightslab, Organon, Landos, McKesson, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Prometheus, Protagonist, Reistone, Roche, Sandoz, Second Genome, Sorriso, Takeda, Teva, Topivert, Ventyx, Viatris, Vividion; lecture: AbbVie, Ferring, Galapagos, Janssen, Pfizer, Takeda, Bristol-Myers Squibb.
MG: employee & shareholder of Pfizer AG.
AB: employee of Pfizer Healthcare India & shareholder of Pfizer.
JW, DB & IM: employees & shareholders of Pfizer.
BGF: consultant/on advisory board: AbbVie, AbolerIS, AgomAB, AllianThera, Amgen, AnaptysBio, Applied Molecular Transport, Arena, Avoro Capital, Atomwise, BIOJAMP, Biora, Boehringer Ingelheim, Boxer, Celsius, Celgene/Bristol-Myers Squibb, Connect, Cytoki, Disc Medicine, Duality, EcoR1, Eli Lilly, Equillium, Ermium, First Wave, FirstWord, Galapagos, Galen Atlantica, Genentech/Roche, Gilead, Gossamer, GSK, Hinge, HotSpot, InDex, Imhotex, Immunic, JAK, Janssen, Japan Tobacco, Kaleido, Landos, Leadiant, L.E.K., Lenczner Slaght, LifeSci, Lument AB, Millennium, MiroBio, Morgan Lewis, Morphic, Mylan, OM, Origo, Orphagen, Pandion, Pendopharm, Pfizer, Prometheus Therapeutics and Diagnostics, Play to Know AG, Progenity, Protagonist, PTM, Q32, Rebiotix, REDX, Roche, Sandoz, Sanofi, Seres, Silverback, Surrozen, Takeda, Teva, Thelium, TiGenix, Tillotts, Ventyx, VHSquared Ltd., Viatris, Ysios, YSOPIA, Zealand; speaker: AbbVie, Janssen, Takeda; Alimentiv Senior Scientific Director, provides central reading services; not a company employee, no equity stake; shareholder: Gossamer.

Introduction

Up to 50% of patients (pts) with inflammatory bowel disease have one or more extraintestinal manifestations (EIMs), which are independent risk factors for poor quality of life and greater disability.¹ Here, we evaluated EIM resolution in patients (pts) with moderate to severe Crohn’s disease (CD) who received risankizumab (RZB), an anti-IL-23p19 monoclonal antibody, versus (vs) placebo (PBO) during the ADVANCE and MOTIVATE induction and FORTIFY maintenance studies.^2,3

Aims & Methods

In this post-hoc analysis of pooled data from ADVANCE and MOTIVATE, data collected from an EIM form, used by investigators to record the presence of 16 pre-specified EIMs (yes/no), were examined. EIM presence at induction baseline (BL), resolution (see Table footnote for definition) at wk 12 with intravenous (IV) RZB 600 mg vs PBO in ADVANCE+MOTIVATE, and maintained resolution at FORTIFY wk 52 among pts treated with subcutaneous (SC) RZB 180 mg or 360 mg vs PBO (withdrew RZB) were assessed.³ Statistical analysis methods are provided in Table footnotes. Nominal P-values for pairwise treatment comparisons are shown.

Results

Previously, EIM resolution at wk 12 in pts with EIMs at BL was evaluated as a ranked secondary endpoint in ADVANCE and MOTIVATE.² A greater proportion of pts achieved EIM resolution at wk 12 with IV RZB 600 mg vs PBO in ADVANCE (38.1% vs 20.5%, nominal P-value = 0.02), but not MOTIVATE (29.5% vs 23.7%, nominal P-value = 0.38). In this pooled analysis, at BL, 323 EIMs were reported for 240 pts in the IV RZB 600 mg arm, and 221 EIMs were reported for 161 pts in the PBO arm; approximately 45% of pts in each arm had ≥1 EIM at BL. The most frequently reported EIMs at BL were peripheral arthropathy (IV RZB 600 mg, 64% [103/161]; PBO, 70.4% [169/240]), anaemia (IV RZB 600 mg, 36% [58/161]; PBO, 28.8% [69/240]), and axial arthropathy (IV RZB 600 mg, 16.1% [26/161]; PBO, 19.2% [46/240]). Together, these EIMs accounted for most reported EIMs across the IV RZB 600 mg (87.9% [284/323]) and PBO (84.6% [187/221]) arms; the incidence of other EIMs were too low for clinically meaningful interpretation (see Table footnotes). A greater proportion of pts achieved resolution of any EIM at wk 12 vs PBO (P = 0.031) with IV RZB 600 mg (Table). A significantly greater proportion of pts with anaemia or axial arthropathy, but not peripheral arthropathy, at BL achieved resolution of the respective EIM at wk 12 with IV RZB 600 mg vs PBO (anaemia: RZB 600 mg, 26/69 [37.4%]; PBO, 13/58 [22.4%]; adjusted (adj) difference 14.4%, P = 0.049; axial arthropathy: RZB 600 mg, 23/46 [50%]; PBO, 8/26 [30.8%]; adj difference 22.6%, P = 0.042; peripheral arthropathy: RZB 600 mg, 67/169 [39.8%]; PBO, 32/103 [31.2%]; adj difference 6.8%, P = 0.236). With SC RZB 360 mg compared to PBO, a greater proportion of pts with EIMs at BL achieved resolution of EIMs at wk 52 (P = 0.005), and a greater proportion of pts who achieved resolution of any EIM at wk 12 maintained resolution at wk 52 (P=0.014) (Table).

Conclusion

Endpoint	Induction, week 12			Maintenance, week 52
	PBO IV	RZB 600 mg IV	Adjusted difference (%) RZB 600 mg IV vs PBO IV, P-value	Withdrawal (PBO SC)	RZB 180 mg SC	Adjusted difference (%) RZB 180 mg SC vs withdrawal (PBO SC), P-value	RZB 360 mg SC	Adjusted difference (%) RZB 360 mg SC vs withdrawal (PBO SC), P-value
Proportion of patients with any EIMs at induction BL, % (n/N)	44.5% (161/362)	45.5% (240/527)		48.7% (80/164)	45.9% (72/157)		48.9% (69/141)
Proportion of patients with resolution of EIMs at week 12 or week 52 in patients with any EIMs at induction BL, % (n/N)	22.5% (36/161)	34.5% (83/240)	9.6%, P=0.031	36.3% (29/80)	41.7% (30/72)	7.5% P=0.283	52.2% (36/69)	20.7%, P=0.005
Proportion of patients with maintenance of resolution of EIMs at FORTIFY week 52 in patients with EIMs at induction BL and who met resolution of EIMs at week 0 of the maintenance period, % (n/N)				45% (18/40)	45.9% (17/37)	3.1%, P=0.764	71.9% (23/32)	25.4%, P=0.014
BL, baseline; EIM, extraintestinal manifestation; PBO, placebo; RZB, risankizumab. EIM resolution was derived by summarizing the binary Yes/No responses from the 16 component questions in the EIM form. Additional EIMs captured on EIM form, along with their prevalence in the population at induction BL (600 mg RZB IV, N=240; PBO IV, N=161), are as follows (n [%]): oral aphthous ulcers, 600 mg RZB IV; 20 (8.3); PBO IV, 17 (10.6), erythema nodosum, 600 mg RZB IV, 7 (2.9); PBO IV, 7 (4.3), nephrolithiasis, 600 mg RZB IV, 7 (2.9); PBO IV, 0, uveitis 600 mg RZB IV, 1 (0.4); PBO IV, 2 (1.2), primary sclerosing cholangitis, 600 mg RZB IV, 1 (0.4); PBO IV, 2 (1.2), chronic obstructive pulmonary disease, 600 mg RZB IV, 0; PBO IV, 1 (0.6), venous thromboembolism 600 mg RZB IV, 1 ( 0.4); PBO IV, 1 ( 0.6), pyoderma gangrenosum, 600 mg RZB IV, 1 (0.4); PBO IV, 1 (0.6), iritis, 600 mg RZB IV, 0; PBO IV, 1 (0.6), Sweet's syndrome, 600 mg RZB IV, 1 (0.4); PBO IV, 1 (0.6), autoimmune hepatitis, 600 mg RZB IV, 0; PBO IV, 0, bronchiectasis, 600 mg RZB IV, 0; PBO IV, 1 (0.6), episcleritis, 600 mg RZB IV, 0; PBO IV, 0. Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used for efficacy analyses. Treatment differences between each RZB dose and PBO were calculated using a normal approximation to the binomial distribution. P-values for pairwise treatment comparisons were provided within each subgroup category based on the Cochran-Mantel-Haenszel test adjusted for study (ADVANCE, MOTIVATE) and strata (number of prior biologics failed (0, 1, >1) and baseline steroid use [Yes, No]).

Among CD pts with EIMs at BL, induction treatment with IV RZB 600 mg led to resolution of EIMs, in particular anaemia and axial arthropathy, while maintenance treatment with SC RZB 360 mg was effective in sustaining EIM resolution through wk 52

References

1. Marinelli C, et al. Gastroenterology Research and Practice. 2019 Aug 21;2019:1–10.
2. D’Haens G, et al. The Lancet. 2022 May;399(10340):2015–30.
3. Ferrante M, et al. The Lancet. 2022 May;399(10340):2031–46.

Disclosure

Subrata Ghosh: SG has received consulting fees from AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Gilead, Galapagos, Janssen, Pfizer, and Receptos; speaker fees from AbbVie, Falk Pharma, Pfizer, Ferring, Janssen, Shield, and Takeda
Marc Ferrante: Research grants from: AbbVie, Amgen, Biogen, EG, Janssen, Pfizer, Takeda and Viatris; Consultancy fees from: AbbVie, Agomab Therapeutics, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Janssen-Cilag, Medtronic, MSD, Pfizer, Regeneron, Samsung Bioepis, Sandoz, Takeda and ThermoFisher; Speakers’ fees from: AbbVie, Amgen, Biogen, Boehringer Ingelheim, Falk, Ferring, Janssen-Cilag, Lamepro, MSD, Pfizer, Sandoz, Takeda, Truvion Healthcare and Viatris
Britta Siegmund: Consultant for AbbVie, Arena, BI, BMS, Celgene, Falk, Galapagos, Janssen, Lilly, Pfizer, Prometheus, and Takeda; and received speaker’s fees from AbbVie, CED Service GmbH, Falk, Ferring, Janssen, Novartis, Pfizer, and Takeda
Takehiro Arai: Nothing to disclose
Walter Reinisch WR has served as a speaker for AbbVie, Celltrion, Falk Pharma GmbH, Ferring, Janssen, Galapagos Medice, MSD, Roche, Pfizer, Pharmacosmos, Shire, Takeda, Therakos, as a consultant for AbbVie, Amgen, AOP Orphan, Arena Pharmaceuticals, Astellas, Astra Zeneca, Bioclinica, Boehringer Ingelheim, Bristol Myers Squibb, Calyx, Celgene, Celltrion, Eli Lilly, Falk Pharma GmbH, Ferring, Galapagos, Gatehouse Bio Inc., Genentech, Gilead, Grünenthal, ICON, Index Pharma, Inova, Janssen, Landos Biopharma, Medahead, MedImmune, Microbiotica, Mitsubishi Tanabe Pharma Corporation, MSD, Novartis, OMass, Otsuka, Parexel, Periconsulting, Pharmacosmos, Pfizer, Protagonist, Provention, Quell Therapeutics, Sandoz, Seres Therapeutics, Setpointmedical, Sigmoid, Sublimity, Takeda, Teva Pharma, Therakos, Theravance, Zealand, as an advisory board member for AbbVie, Amgen, Astra Zeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Galapagos, Janssen, Mitsubishi Tanabe Pharma Corporation, MSD, Pharmacosmos, Pfizer, Sandoz, Takeda, and has received research funding from AbbVie, Janssen, MSD, Sandoz, Sanofi, Takeda.
David Hudesman Consultant: AbbVie, BMS, Fresenius Kabi, Janssen, Pfizer, Prometheus, Takeda, UCB
Research Support: Janssen and Pfizer
Edouard Louis: Research grant: Janssen, Pfizer, Ferring, Falk, AbbVie and Takeda; educational grant: AbbVie, Janssen, Fresenius-Kabi and Takeda; speaker fees: AbbVie, Falk, Ferring, Janssen, Pfizer, Galapagos, BMS and Takeda; advisory board: Abbvie, Celgene, Ferring, Janssen, BMS, Pfizer, and Takeda, Galapagos, Gilead, Arena, Eli Lilly; consultant: Abbvie
Naomi Martin, Joanne Rizzo,Kristina Kligys, Yafei Zhang, Javier Zambrano, and Jasmina Kalabic are AbbVie employees and may own AbbVie stock and/or options.