Introduction

Tumor necrosis factor–like cytokine 1A (TL1A) is a mediator of inflammation and fibrosis in CD. Tulisokibart, an anti-TL1A monoclonal antibody, demonstrated robust efficacy without adverse safety signals during the 12-week induction period in adults with moderately to severely active CD in the multicenter, open-label, phase 2a APOLLO-CD study.¹ We report long-term efficacy and safety data for tulisokibart from the APOLLO-CD open-label extension (OLE).

Aims & Methods

Responders to tulisokibart induction at 12-weeks (defined as a decrease from baseline in CD activity index [CDAI] of ≥100 points or CDAI <150 at week 12) were given the opportunity to enter the OLE study, whereas 12-week non-responders discontinued the study. At week 14, responders were randomized to receive intravenous tulisokibart 100 mg or 250 mg every 4 weeks until week 170. Reported here are the endoscopic, clinical, and biomarker endpoints through week 50 in the intention-to-treat population. Safety was evaluated in all patients who received ≥1 dose of tulisokibart. Descriptive statistics were used to summarize observed data.

Results

53 of 55 patients completed the 12-week induction period, 37 were considered induction responders and were randomized to receive tulisokibart 100 mg (n=19) or 250 mg (n=18). A greater proportion of patients who were biologic-naive entered the OLE in the tulisokibart 250 mg vs 100 mg group (44% vs 21%). Improvements in clinical, endoscopic, and biomarker outcomes observed were generally maintained through week 50 in both dose groups. At week 50, a greater proportion of patients achieved clinical and endoscopic outcomes with tulisokibart 250 mg vs 100 mg (Table). In addition, normalization of high-sensitivity C-reactive protein (hsCRP) favored the 250 mg dose vs the 100 mg dose. During the 12-week induction period, 78% of patients reported AEs. At week 50, AEs were reported in 83% and 84% of patients receiving tulisokibart 250 mg and 100 mg, respectively, and were mostly mild-to-moderate in severity. Serious AEs occurred in 6% of patients receiving tulisokibart 250 mg and 11% of patients receiving tulisokibart 100 mg. The most frequently occurring AEs of special interest (>10% of patients in either dose group) were urinary tract infection (11% vs 16%), COVID-19 (11% vs 11%), upper respiratory tract infection (6% vs 16%), bronchitis (11% vs 0%), clostridium difficile infection (11% vs 0%), and influenza (0% vs 11%).

Conclusion

At week 50, maintenance of treatment efficacy was generally observed in 12-week induction responders. A trend for higher maintenance efficacy with tulisokibart 250 mg vs 100 mg maintenance treatment was observed at week 50. Tulisokibart was well tolerated with no safety signals identified through 50 weeks of treatment. Larger trials are needed to confirm these findings.

Table. Clinical, endoscopic and biomarker outcomes at week 12 and among 12-week induction responders at week 50
	Week 12 Tulisokibarta (n = 55)	Week 50 Tulisokibart 100 mg (n = 19)	Week 50 Tulisokibart 250 mg (n = 18)
Endoscopic responseb	13 (24)	3 (16)	5 (28)
Clinical remissionc	27 (49)	8 (42)	10 (56)
Clinical responsed	37 (67)	11 (58)	12 (67)
Composite endoscopic and clinical responsee	9 (16)	3 (16)	4 (22)
Composite biomarker and clinical responsef	n = 49 17 (35)	n = 16 4 (25)	n = 17 6 (35)
Normalization of hsCRPg	n = 36 5 (14)	n = 9 0	n = 16 5 (31)
Normalization of fecal calprotectinh	n = 44 6 (14)	n = 14 2 (14)	n = 16 2 (13)
All data are n (%). aDuring the 12-week induction period, patients received intravenous tulisokibart 100 mg on day 1 and 500 mg at weeks 2, 6, and 10. All patients treated with tulisokibart with baseline CDAI and SES-CD scores were included in the full analysis set population. bEndoscopic response was defined as a decrease in SES-CD total score ≥50% from baseline. cClinical remission was defined as CDAI score <150. dClinical response was defined as either a decrease of ≥100 points in CDAI from baseline or CDAI score <150. eComposite endoscopic and clinical response was defined as a decrease in SES-CD score ≥50% from baseline and either a decrease of ≥100 points in CDAI from baseline or CDAI score <150. fComposite biomarker and clinical response was defined as a decrease in hsCRP or fecal calprotectin ≥50% from baseline and either a decrease of ≥100 points in CDAI from baseline or CDAI score <150 (evaluated in patients with ≥1 elevated biomarker at baseline). gNormalization of hsCRP was defined as a concentration of <5 mg/L among patients with elevated levels at baseline. hNormalization of fecal calprotectin was defined as a concentration of <250 µg/g among patients with elevated levels at baseline.

References

1. Feagan BG, et al. J Crohns Colitis. 2023;17(Supplement_1):i162-i164.

Disclosure

CAS is a consultant/advisory board for AbbVie, BMS, Boomerang, Buhlmann, Janssen, Lilly, Napo Pharmaceuticals, Pfizer, Prometheus Biosciences, Prometheus Labs, Roivant, Takeda, Trellus Health; speaker for CME activities for AbbVie, Janssen, Pfizer, Takeda; grant support from AbbVie, Janssen, Pfizer, Takeda.
RWL reports advisory board membership for AbbVie, Aspen, BMS, Celgene, Celltrion, Chiesi, Ferring, Glutagen, Hospira, Janssen, Lilly, MSD, Novartis, Pfizer, Prometheus Biosciences, Takeda; research grant recipient: Celltrion, Shire, Janssen, Takeda, Gastroenterological Society of Australia, NHMRC, Gutsy Group, Pfizer, Joanna Tiddy grant, McKusker Charitable Foundation.
JKA, BD, and MY are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
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, Envied Biosciences, Evommune, Ferring, Fresenius Kabi, Fiat, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Imhotex, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Kaleido, Kallyope, Merck & Co., Inc., Rahway, NJ, USA, 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.
SD has received consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, Applied Molecular Transport, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion Healthcare, Dr. Falk Pharma, Eli Lilly and Company, Enthera, Ferring, Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB Inc., Vial, and Vifor and lecture fees from AbbVie, Amgen, Ferring, Gilead, Janssen, Mylan, Pfizer, and Takeda.
BGF is a consultant for AbbVie, AbolerIS, AgomAB Therapeutics, Allianthera, Amgen, AnaptysBio, Applied Molecular Transport Inc., Arena Pharma, Atomwise, Avoro Capital Advisors, BioJamp, Biora Therapeutics, Boehringer Ingelheim, Boxer, Bristol Myers Squibb/Celgene, Celsius Therapeutics, Connect BioPharma, Cytoki, Disc Medicine, Duality, EcoR1 Capital, Equillium, Ermium, First Wave, First Word Group, Galapagos, Galen Atlantica, Genentech/Roche, Gilead, GlaxoSmithKline, Gossamer Pharma, Hinge Bio, Hot Spot Therapeutics, Imhotex, Immunic Therapeutics, InDex Pharmaceuticals, JAKAcademy, Janssen, Japan Tobacco Inc., Kaleido Biosciences, Landos Biopharma, Leadiant, L.E.K. Consulting, Lenczner Slaght, LifeSci Capital, Lilly, Lument AB, Millennium, MiroBio, Morgan Lewis, Morphic Therapeutics, Mylan, OM Pharma, Origo BioPharma, Orphagen, Pandion Therapeutics, Pendopharm, Pfizer, Play to Know AG, Prometheus Therapeutics and Diagnostics, Progenity, Protagonist, PTM Therapeutics, Q32 Bio, Rebiotix, REDX, Roche, Sandoz, Sanofi, Seres Therapeutics, Silverback Therapeutics, Surrozen Inc., Takeda, Teva, Thelium, Tigenix, Tillotts, Ventyx Biosciences, VHSquared Ltd., Viatris, Ysios, Ysopia, and Zealand Pharma; on the Speakers’ Bureau for AbbVie, Janssen, and Takeda; and on advisory boards for AbbVie, Amgen, AMT, AnaptysBio, Axio Research, Boehringer Ingelheim, Bristol Myers Squibb/Celgene, EcoR1 Capital, Genentech/Roche, GlaxoSmithKline, InDex Pharmaceuticals, Janssen, Lilly, MiroBio, Morphic, Origo BioPharma, Pfizer, Progenity, Prometheus, REDX Pharma, Sanofi, Takeda, Teva, and Tillotts Pharma.

Introduction

The Epi-IBD cohort is a prospective European population-based cohort of 1,390 patients diagnosed in 2010 and 2011 with inflammatory bowel disease (IBD) according to Copenhagen criteria in centres from Eastern and Western European countries.

Aims & Methods

The study aims at describing differences in incidence, treatment strategies, disease course and prognosis of Crohn’s disease (CD) across Eastern and Western Europe. CD patients were followed prospectively from the time of diagnosis until December 31^st, 2020, death, emigration or loss of follow-up. Clinical data on surgery, hospitalizations, and medical treatment, were captured throughout the follow-up period and entered into a validated web-database, www.epi-ibd.org. Associations between surgery and covariates were analysed by multivariate Cox regression analyses.

Results

In total, 482 CD patients aged ≥15 years from 21 centres in 5 Eastern and 11 Western European countries were included. At 10-years follow-up, 101 (21%) patients underwent first intestinal resection and 11 out of these 101 patients (11%) underwent additional resections. Furthermore, 176 (37%) patients had at least one CD related hospitalization. Cancer was diagnosed in 21 (4%) patients, including 4 gastrointestinal cancers. The use of IBD medication was comparable between Eastern and Western European centres apart from 5-aminosalicylic acid agents (Table 1).
During follow-up, 60 out of 360 patients (17%) progressed from non-stricturing-non-penetrating disease (B1) at diagnosis to stricturing or penetrating disease (B2 or B3) while 13 out of 83 patients (16%) with stricturing disease (B2) progressed to penetrating disease (B3). The median time to progression was 28 (IQR: 9-64) months from diagnosis. No patients from Eastern Europe were exposed to biological therapy prior to change in behaviour, compared to 23 out of 66 patients (35%) from Western Europe.
Multivariate Cox regression analysis showed no difference in risk of surgery according to European region (Eastern vs. Western Europe, HR: 0.54, 95%CI: 0.24-1.21). Early intervention with biological therapy (within 6 months) did not influence the risk of surgery (HR:0.75, 95%CI: 0.31-1.83), however early introduction of immunomodulators reduced the risk significantly (HR:0.54, 95%CI: 0.30-0.98). Progression in behaviour from B1 was associated with higher risk of surgery (HR:7.62, 95%CI: 3.91-14.87).

Conclusion

After 10 years of follow-up, 21% underwent intestinal resection and 10% required additional resections. Despite the widespread use of immunomodulators and biological therapy, 16% of the patients had disease behavioural progression, which was associated with higher risk of surgery. Early introduction of immunomodulators was found to be beneficial.

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

Mirikizumab (miri), an anti-IL-23p19 antibody, has shown efficacy in patients with moderately-to-severely active Crohn’s disease (CD) to Week (W)52. We explored the potential relationship between early histologic and endoscopic responses on long term clinical outcomes after 2 years of miri treatment in a double-blind, placebo (PBO)-controlled Phase 2 trial (NCT02891226) in patients with CD.

Aims & Methods

Patients were randomized 2:1:1:2 to 4 treatment arms: miri 1000mg, 600mg, 200mg, and PBO administered intravenously (IV) at W0, W4, and W8. Patients who received miri and achieved ≥1 point improvement at W12 in Simple Endoscopic Score for Crohn’s disease score were re-randomized to either continue their induction IV dose or receive miri 300mg subcutaneously (SC) every 4 weeks up to W52. Subjects reported to experience clinical benefit received 300mg SC from W52 to W104. Biopsies were obtained during endoscopy at W0, W12 and W52 from the edges of any ulcers or from the most inflamed mucosa in the terminal ileum and 4 colonic segments and were scored by blinded central readers. Endpoints were defined post-hoc and prior to analyses (see Table 1). Among patients receiving miri with active histological disease at baseline, we determined the relationship between histologic and/or endoscopic response or remission at W12 and W52 and with clinical remission based on the Crohn’s Disease Activity Index (CDAI), patient-reported outcomes (PRO), and hospitalization rates at W104. Non-responder imputation for CDAI or PRO at W104 was used for patients who have observed histologic and endoscopic outcome value at W52 or W12. Hospitalizations were summarized by observed value. P-values for categorical values were determined with Fisher’s exact test.

Results

At W104, 56.9% patients (N=137) achieved CDAI remission compared to 41.5% of 176 patients at W52. We observed no association between early (W12) histologic, endoscopic, or combined (histo-endo) response and clinical remission (CDAI & PRO) at 2 years. After 2 years, the percentage of patients achieving remission based on CDAI varied according to their response at W52 by histology (60%), endoscopy (25.9%), both histo-endo (56.3%), or neither (10.5%, p=0.006; Table 1). Similarly, the proportion of patients who achieved 2-year clinical remission (by CDAI) varied according to W52 remission by histology (72.7%), endoscopy (40%), both histo-endo (40%) or neither (19.5%, p=0.007). Hospitalization rates during this period were low and varied according to W52 response by histology (16.7%), endoscopy (0%), both (0%) or neither (3.9%, p=0.021).

Table 1. Week 104 clinical remission and hospitalization rates by histologic and endoscopic response at Week 12 and Week 52, and by histologic and endoscopic remission at Week 52

Week 104	Without Histologic or Endoscopic Response	Histologic and Without Endoscopic Response	Endoscopic response Without Histologic	Histologic and Endoscopic Response	P‑value	Without Histologic or Endoscopic Remission	Histologic Without Endoscopic Remission	Endoscopic Without Histologic Remission	Histologic and Endoscopic Remission	P‑value
	Week 12a					Week 12
CDAI remission	60 (12/20)	57.9 (11/19)	50 (2/4)	61.3 (19/31)	>0.999	Due to the low number of patients with endoscopic or histologic remission at Week 12, no data are shown in this quadrant
PRO remission	55 (11/20)	31.6 (6/19)	50 (2/4)	61.3 (19/31)	0.237
Hospitalizations due to CDb	0 (0/42)	3.9 (1/26)	0 (0/8)	3.2 (1/31)	0.426
	Week 52c					Week 52c
CDAI remission	10.5 (2/19)	60 (6/10)	25.9 (7/27)	56.3 (9/16)	0.006	19.5 (8/41)	72.7 (8/11)	40 (6/15)	40 (2/5)	0.007
PRO remission	10.5 (2/19)	30 (3/10)	11.1 (3/27)	68.8 (11/16)	<0.001	12.2 (5/41)	63.6 (7/11)	33.3 (5/15)	40 (2/5)	0.003
Hospitalizations due to CDb	3.9 (1/26)	16.7 (2/12)	0 (0/39)	0 (0/24)	0.021	3.9 (2/52)	5 (1/20)	0 (0/24)	0 (0/5)	0.809
Note: Data displayed as % (n/N). For categorical outcomes, p-values are based on Fisher’s exact test. Histologic response was defined as: a) absence of neutrophils in epithelium, and absence of epithelial damage, erosions and ulceration or b) decrease of either RHI or modified GHAS ≥50% from baseline. Endoscopic response is defined as a 50% reduction from baseline in SES-CD. Histologic remission was defined as absence of mucosal neutrophils, epithelial damage, erosions, and ulceration. Endoscopic remission is defined as SES-CD of <4 ileal-colonic or <2 for isolated ileal disease, and no subscore of >1. CDAI remission is defined as CDAI Total Score <150; PRO remission is defined as (7-day average of SF ≤2.5 and no worse than baseline) + (7-day average of AP≤1 and no worse than baseline). SF captures number of liquid or very soft stools; AP score is classified as 0=none, 1=mild, 2=moderate, 3=severe. Abbreviations: AP= abdominal pain; CDAI= Crohn’s Disease Activity Index; GHAS= Global Histologic Disease Activity Score; PRO= patient-reported outcomes; N=number of patients in the histologic/endoscopic response group; n = number of patients in the specified category; RHI= Robarts Histologic Index; SES-CD=Simple Endoscopic Score for Crohn’s Disease; SF= stool frequency. a Patients with Active histologic disease at Baseline and with both Endoscopic and Histologic measures at Week 12. b Defined as serious adverse event due to hospitalization. Week 12 columns depict hospitalizations from Weeks 12-52. Week 52 columns depict hospitalizations from Weeks 52-104. c Patients with Active histologic disease at Baseline and with both Endoscopic and Histologic measures at Week 52.

Conclusion

In CD patients treated with miri for 2 years, long term clinical remission (CDAI, PRO) was significantly correlated with histologic response alone as well as combined histologic-endoscopic response at Week 52, but not at Week 12. The small sample size was likely a limitation. This data will be further studied in Phase 3 trials.

Disclosure

VJ reports consulting/advisory board fees from AbbVie, Alimentiv Inc (formerly Robarts Clinical Trials), Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Reistone Biopharma, Roche, Sandoz, Second Genome, Takeda, Teva, Topivert, Vividion; speaker’s fees from, Abbvie, Ferring, Galapagos, Janssen, Pfizer, Shire, Takeda, Fresenius Kabi. 
WR reports lecture fees from AbbVie, Actelion, Alpha Wasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring, Genentech, Grunenthal, Johnson & Johnson, Millennium, Merck, NovoNordisk, Nycomed, Pfizer, Pharmacosmos, Schering-Plough, Salix, Takeda, UCB Pharma, and Vifor; consultant fees from AbbVie, Actelion, Alpha Wasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring, Genentech, Grunenthal, Johnson & Johnson, Millennium, Merck, NovoNordisk, Nycomed, Pfizer, Pharmacosmos, Schering-Plough, Salix, Takeda, UCB Pharma, and Vifor; and serves as an advisory board member for AbbVie, Actelion, Alpha Wasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring, Genentech, Grunenthal, Johnson & Johnson, Millennium, Merck, NovoNordisk, Nycomed, Pfizer, Pharmacosmos, Schering-Plough, Salix, Takeda, UCB Pharma, and Vifor.
GDH reports that his institution has received fees for his clinical trial activities with Centocor J&J.
NH has served as an advisory board member or consultant for Eli Lilly and Company, Abbvie Inc., Bristol Meyer Squibb, Inc., and PathAI, Inc.
RP reports consulting fees from Seres Therapeutics, Eli Lilly, Protagonist, Genentech, and Robarts Clinical Trials.
MP, ZL, RH, HC are employees and minor shareholders of Eli Lilly and company. 
FM served as speaker for Abbvie, Arena, Biogen, Bristol-Myers Squibb, Falk, Ferring, Hospira, Janssen, Laboratórios Vitoria, Pfizer, Lilly, Merck Sharp & Dohme, Sandoz, Takeda, UCB, Vifor.

Introduction

Objective: Tumor necrosis factor–like cytokine 1A (TL1A) regulates pro-inflammatory cytokines and fibrosis. PRA023 is an anti-TL1A monoclonal antibody in development for multiple inflammatory/fibrotic diseases incorporating a precision approach with a predictive genetic-based diagnostic (Dx) tool. This placebo-controlled, double-blind phase 2 study assessed efficacy and safety of PRA023 induction treatment in adults with moderately to severely active ulcerative colitis (UC).

Aims & Methods

Patients with a modified Mayo score (mMS) of 4 to 9, centrally read endoscopy subscore of ≥2, rectal bleeding subscore of ≥1, and history of insufficient response, loss of response, and/or intolerance to conventional and/or advanced therapies (≤4 advanced agents from ≤3 classes allowed) were eligible. Patients were stratified by prior biologic exposure and Dx status and randomized 1:1 to placebo or intravenous PRA023 (1000 mg on day 1, 500 mg at weeks 2, 6, and 10). The primary endpoint was clinical remission per mMS at week 12. Analyses of ranked secondary endpoints were multiplicity-controlled.

Results

Of the 135 patients, 60/67 (89.6%) in the placebo arm and 68/68 (100%) in the PRA023 arm completed the 12-week induction period. Baseline characteristics were similar. A significantly greater proportion of patients who received PRA023 achieved the primary endpoint of clinical remission (26.5% PRA023 vs 1.5% placebo, ∆25.0%, p<0.0001) at week 12 (Table 1). All ranked secondary endpoints for cohort 1 significantly favored drug relative to placebo, including symptomatic remission (19.1% PRA023 vs 6.0% placebo, ∆13.1%, p=0.02), mucosal healing (30.8% PRA023 vs 3.5% placebo, ∆27.3%, p<0.0001), and IBDQ response (82.4% PRA023 vs 49.3% placebo, ∆33.1%, p<0.0001; Table 1). Exposure to prior advanced therapy, antidrug antibody status, and concomitant therapy did not have a major effect on efficacy. Statistically significant reductions in symptom scores (partial Mayo score) were observed in patients receiving PRA023 as early as week 2. C-reactive protein and fecal calprotectin levels were significantly reduced throughout the treatment period with PRA023 compared to placebo. An enhanced treatment effect was observed for the prespecified Dx+ subgroup, with 37.5% for both placebo-adjusted clinical remission and endoscopic improvement. The rates of treatment-emergent adverse events (AEs) were similar between the 2 arms with no serious AEs or AEs leading to study drug discontinuation in the PRA023 arm. There were no safety signals identified from the study.

Table 1: Primary and Secondary Efficacy Endpoints

	Placebo (N=67) N (%)	PRA023 (N=68) N (%)	Placebo-adjusted treatment effect % (95% CI)	P-value
Clinical remission	1 (1.5)	18 (26.5)	25.0 (13.9–36.6)	<0.0001
Endoscopic improvement	4 (6.0)	25 (36.8)	30.8 (17.4–43.2)	<0.0001
Clinical response	15 (22.4)	45 (66.2)	43.8 (27.4–56.9)	<0.0001
Symptomatic remission	4 (6.0)	13 (19.1)	13.1 (1.8–24.6)	0.0223
Mucosal healing	2 (3.5)*	20 (30.8)†	27.3 (14.3–39.6)	<0.0001
Histologic improvement	10 (17.5)*	30 (46.2)†	28.6 (12.1–42.9)	0.0009
Histologic-endoscopic mucosal improvement	2 (3.5)*	20 (30.8)†	27.3 (14.3–39.6)	<0.0001
Inflammatory Bowel Disease Questionnaire response	33 (49.3)	56 (82.4)	33.1 (17.2–46.8)	<0.0001

P values for testing the treatment difference are based on Cochran–Mantel–Haenszel test adjusted for prior biologic exposure status and Dx status. *n=56; †n=56.

Conclusion

PRA023 was effective with favorable tolerability for the induction of clinical remission and endoscopic improvement in moderately to severely active UC. A phase 3 study will be conducted to confirm these findings. The enhanced treatment effect in the Dx+ subgroup from cohort 1 is being further evaluated in the Dx+ expansion cohort 2.

Disclosure

BES has served as a consultant for or received speaker’s fees from AbbVie, Abivax, Adiso Therapeutics, Alimentiv, Amgen, Arena Pharmaceuticals, Artizan Biosciences, Artugen Therapeutics, AstraZeneca, Bacainn Therapeutics, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Calibr, Celltrion Healthcare, ClostraBio, Connect Biopharma, Cytoki Pharma, Eli Lilly and Company, Entera, Evommune, Ferring, Fresenius Kabi, Galapagos, Gilead, Genentech, GSK, Gossamer Bio, HMP Acquisition, Imhotex, Immunic, InDex Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Ironwood Pharmaceuticals, Janssen, Johnson & Johnson, Kaleido, Kallyope, Merck, MiroBio, Morphic Therapeutic, MRM Health, OSE Immunotherapeutics, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, RedHill Biopharma, Sun Pharma Global, Surrozen, Synlogic, Takeda, Target RWE, Theravance Biopharma R&D, TLL Pharmaceutical, USWM Enterprises, Ventyx Biosciences, and Viela Bio and has received stock options from Ventyx Biosciences.
LPB has served as a consultant for or has received fees from AbbVie, Allergan, Alma, Amgen, Applied Molecular Transport, Arena, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion Healthcare, Eli Lilly and Company, Enterome, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, Hikma, Index Pharmaceuticals, Inotrem, Janssen, MSD, Mylan, Oppilan Pharma, OSE Immunotherapeutics, Nestlé, Norgine, Roche, Pandion Therapeutics, Pfizer, Pharmacosmos, Samsung Bioepis, Sandoz, sterna biologicals, Sublimity Therapeutics, Takeda, Theravance Biopharma, Tillotts Pharma, and Vifor; has received grants from AbbVie, Fresenius Kabi, MSD, and Takeda; and has stock options from CTMA.
SD has received consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, Applied Molecular Transport, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion Healthcare, Dr. Falk Pharma, Eli Lilly and Company, Enthera, Ferring, Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB Inc., Vial, and Vifor and lecture fees from AbbVie, Amgen, Ferring, Gilead, Janssen, Mylan, Pfizer, and Takeda.
DTR has served as a consultant for AbbVie, AltruBio, Aslan Pharmaceuticals, Athos Therapeutics, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Celgene Chronicles, Corp/Syneos, ClostraBio, Connect Biopharma, Eco R1, Eli Lilly and Company, Genentech/Roche, Gilead Sciences, Iterative Health, Janssen Pharmaceuticals, Kaleido, Pfizer, Prometheus Biosciences, Reistone Biopharma, Seres Therapeutics, Takeda, Target RWE, and Trellus Health and has received grant support from Takeda, Helmsley Charitable Trust, and the Gastro-Intestinal Research Foundation.
SV has received grants from AbbVie, Galapagos, Johnson & Johnson, Pfizer, and Takeda and consulting and/or speaking fees from AbbVie, Abivax, AbolerIS Pharma, AgomAb, Alimentiv, Arena, AstraZeneca, Avaxia, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, CVasThera, Cytoki Pharma, Dr. Falk Pharma, Ferring, Galapagos, Genentech/Roche, Gilead, GSK, Hospira, IMIDomics, Janssen, Johnson & Johnson, Eli Lilly and Company, Materia Prima, MiroBio, Morphic, MrMHealth, Mundipharma, MSD, Pfizer, ProDigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance, Tillotts Pharma, and Zealand Pharma.
OL, AL, DDN, and JDL are employees and shareholders of Prometheus Biosciences.
AWK has nothing to disclose.
JL has received speaker fees from AstraZeneca, MSD, Janssen, and Gilead and research grants from Johnson & Johnson.
RK has received grants from Janssen and Takeda.
JK has received consultation fees, research grants, or honoraria from AbbVie, Egis, Janssen, Nestlé, Nutricia, and Takeda.
CM has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma, BIOJAMP, Bristol Myers Squibb, Celltrion Healthcare, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Takeda, Pendopharm, Pfizer, Prometheus Biosciences, Roche, and Sanofi; speaker's fees from AbbVie, Amgen, AVIR Pharma, Alimentiv, Bristol Myers Squibb, Ferring, Fresenius Kabi, Janssen, Takeda, Pendopharm, and Pfizer; royalties from Springer Publishing; and research support from Ferring and Pfizer.
TER has been a speaker for Takeda Pharmaceuticals, Janssen, Pfizer, Bristol Myers Squibb, and Abbvie; has served on advisory boards for AbbVie, Ardelyx, Arena, Boehringer Ingelheim, Bristol Myers Squibb/Celgene, Eli Lilly and Company, Ferring, Genentech/Roche, Gilead, Intercept, Iterative Scopes, Janssen, Pfizer, Prometheus Biosciences, Sanofi, and Takeda; and has been a shareholder for Iterative Scopes.
RP has been a consultant for Abbott, AbbVie, Abivax, Alimentiv (formerly Robarts), Amgen, Arena, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion Healthcare, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly and Company, Ferring, Galapagos, Fresenius Kabi, Genentech, Gilead Sciences, GSK, BIOJAMP, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Takeda, Theravance Biopharma, Trellus, Viatris, Ventyx, and UCB; has received speakers fees from AbbVie, Amgen, Arena, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Ferring, Fresenius Kabi, Gilead Sciences, Janssen, Merck, Organon, Pfizer, Roche, Sandoz, Shire, and Takeda; and has served on advisory boards for AbbVie, Alimentiv (formerly Robarts), Amgen, Arena, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Ferring, Fresenius Kabi, Genentech, Gilead Sciences, GSK, BIOJAMP, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Shire, Sublimity Therapeutics, Takeda, and Ventyx.
BGF has served as a consultant for AbbVie, AbolerIS Pharma, AgomAb, AllianThera, Amgen, AnaptysBio, Applied Molecular Transport, Arena, Avoro Capital Advisors, Atomwise, BIOJAMP, Biora Therapeutics, Boehringer Ingelheim, Boxer, Celsius Therapeutics, Bristol Myers Squibb/Celgene, Connect Biopharma, Cytoki, Disc Medicine, Duality, EcoR1 Capital, Eli Lilly and Company, Equillium, Ermium, First Wave, First Word Group, Galapagos, Galen Atlantica, Genentech/Roche, Gilead, Gossamer Bio, GSK, Hinge Bio, HotSpot Therapeutics, Index Pharma, Imhotex, Immunic Therapeutics, JAK Academy, Janssen, Japan Tobacco, Kaleido, Landos Biopharma, Leadiant, L.E.K. Consulting, Lenczner Slaght, LifeSci Capital, Lument AB, Millennium, MiroBio, Morgan Lewis, Morphic Therapeutics, Mylan, OM Pharma, Origo Biopharma, Orphagen, Pandion Pharma, Pendopharm, Pfizer, Prometheus Therapeutics, PlayToKnow AG, Progenity, Protagonist Therapeutics, PTM Therapeutics, Q32 Bio, Rebiotix, REDX, Roche, Sandoz, Sanofi, Seres Therapeutics, Silverback Therapeutics, Surrozen, Takeda, Teva, Thelium, TiGenix, Tillotts Pharma, Ventyx Biosciences, VHsquared, Viatris, Ysios, Ysopia, Zealand Pharma; on the speaker’s bureau for AbbVie, Janssen, and Takeda; and on advisory boards for AbbVie, Amgen, AMT, AnaptysBio, Boehringer Ingelheim, Bristol Myers Squibb/Celgene, Eli Lilly and Company, Genentech/Roche, Janssen, MiroBio, Origo BioPharma, Pfizer, Prometheus, REDX, Sanofi, Takeda, Tillotts Pharma, Teva, Progenity, Index, EcoR1 Capital, Morphic, GSK, and Axio Research.
ST has received consulting fees from Robarts Clinical Trials and Prometheus Biosciences and owns stock in Prometheus Biosciences; is a member of steering committees of Janssen, AbbVie, Boehringer Ingelheim, Gilead, Celgene, and Bristol Meyers Squibb; has received speaker honoraria from AbbVie, Takeda, Janssen, Ferring, Pfizer, and Celltrion; and has served on advisory committees of Janssen, Takeda, AbbVie, Eli Lilly, Pfizer, Gilead, Galapagos, and Roche.
DPBM has received consulting fees from Prometheus Biosciences, Prometheus Laboratories, Gilead Sciences, Boehringer-Ingelheim, Pfizer, Prometheus Laboratories, Takeda, Palatin Technologies, and owns stock in Prometheus Biosciences.

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.