Introduction

Risankizumab is an interleukin-23 inhibitor approved for the treatment of Crohn’s disease (CD). Its efficacy and safety have recently been demonstrated in trial-setting but there is yet limited evidence of its real-world effectiveness, especially on the middle- and long-term.

Aims & Methods

Using prospective data from the Dutch Initiative on Crohn and Colitis (ICC) Registry, we aimed to evaluate the effectiveness and adverse events of risankizumab in patients with difficult-to-treat CD, defined as the failure of advanced therapies with at least two different mechanisms of action¹. The primary endpoint was corticosteroid-free (CSF) clinical remission at week (W) 24. CSF clinical remission was defined as Harvey Bradshaw Index (HBI) ≤ 4 and no use of systemic corticosteroids at the time of the visit. As secondary outcomes, we examined clinical remission, biochemical remission (faecal calprotectin (FC) level ≤ 250μg/g) and combined clinical and biochemical remission at W24. Furthermore, remission rates between patients without history of bowel resection (i.e. surgery-naïve) and with bowel resection (i.e. surgery-experienced) at W24, drug survival and adverse events were assessed. Patients were included in the analysis if they received at least one intravenous dose of risankizumab before the 28^th of February 2025. Patients without available remission data at W24 and who remained on treatment were excluded from the W24 analysis population. Patients who discontinued treatment before W24 due to non-response, adverse events or loss to follow-up were considered non-responders.

Results

Eighty-five patients were included in the current analysis; 56 (65.9%) were female. Patients had a median disease duration of 16.0 years (IQR 14.0). Surgery history was available for 83 patients; 33 (39.8%) patients did not undergo surgery, while 50 (60.2%) were considered as surgery-experienced. At baseline, HBI was available for 72 patients; the median HBI was 6 (IQR 5); 24 (33.3%) patients had an HBI ≤ 4. Biochemical data were available for 19 (79.2%) patients in clinical remission: only one (5.3%) was in biochemical remission. At W24, HBI was available for 62 patients; 34 (54.8%) patients were in CSF clinical remission. Independent of CSF status, 62.9% (39/62) of the patients were in clinical remission. FC levels at W24 were available for 55 patients; 17 (30.9%) patients were in biochemical remission. Remission rates were not influenced by surgery history (Table 1). Over time, 16.5% (14/85) patients stopped risankizumab, after a median treatment duration of 182 days (IQR 188). Three (21.4%) patients discontinued risankizumab before W12, three (21.4%) between W12 and W24, and eight (57.2%) between W24 and W52. Reasons for discontinuation were non-response (42.9%), loss of response (42.9%) and adverse events (14.2%). A total of 83 adverse events were reported in 51 patients. Most common adverse events included respiratory infections (13.2%), skin problems (10.8%) and herpes zoster infections (8.4%). No hospitalisation or death were reported.

Conclusion

This prospective real-world study demonstrates the clinical effectiveness and the favourable safety profile of risankizumab at W24 in a difficult-to-treat Crohn’s disease population, including a high proportion of patients with bowel resection.

References

1. Parigi TL, D'Amico F, Abreu MT, Dignass A, Dotan I, Magro F, Griffiths AM, Jairath V, Iacucci M, Mantzaris GJ, O'Morain C, Reinisch W, Sachar DB, Turner D, Yamamoto T, Rubin DT, Peyrin-Biroulet L, Ghosh S, Danese S. Difficult-to-treat inflammatory bowel disease: results from an international consensus meeting. Lancet Gastroenterol Hepatol. 2023 Sep;8(9):853-859. doi: 10.1016/S2468-1253(23)00154-1. Epub 2023 Jul 6. PMID: 37423233.

Disclosure

LMMV - none FDMvS - adviser and/or speaker for Takeda, Galapagos, Dr. Falk, Lilly, and Janssen-Cilag; received an unrestricted grant from Takeda MRN - none ACdV - advisory boards for Takeda, Janssen, Bristol Myers Squibb, Abbvie, Pfizer, and Galapagos; research grants from Takeda, Janssen, and Pfizer AEvdMDJ - speaker fee from AbbVie, Alfasigma, Ferring, Janssen Pharmaceuticals, Takeda, Tramedico, and Vedanta; grants from Norgine, Cablon, Alfasigma, and ZonMW MCV - speaker fees from Janssen-Cilag, Galapagos, and Ferring B.V. WAvD - none WSN - none TER - none RLW - speaker fee from Abbvie, Ferring, and Pfizer BJ - none AGLB - none PV - speaker fee from Takeda, Abbvie, Janssen, Alfa Sigma, Lilly, and BMS BO - advisory boards of Takeda, BMS, Galapagos, Janssen, AbbVie, BMS, and Ferring; grants from Takeda, Pfizer, Galapagos, Ferring, Celltrion, BMS, and AbbVie ML - consultancy/lecture fees from AbbVie, Bristol Myers Squibb, Eli Lilly, Galapagos, Janssen-Cilag, Johnson & Johnson, Medtronic, Pfizer, Takeda, and Tillotts Pharma; grants from Alfasigma, the Netherlands Federation of University Medical Centres, TKI, and ZonMW JELS - none LAAPD - served on advisory boards as a speaker for Abbvie, Alfasigma, Janssen, and Pfizer; independent research funding from Pfizer HHF - none MJP - speaker fee from BMS, Janssen Cilag, and Takeda; non-restricted research grants from Horizon 2020, ZONMW (Dutch national research fund), MLDS, Takeda, Johnson and Johnson, Abbvie, and Galapagos MD - speaking fee from Bristol Meyers Squibb, Takeda, Galapagos, Janssen, and Dr. Falk; advisory board fees from Abbvie, Bristol Meyers Squibb, Celltrion, Galapagos/Alfasigma, Janssen, Takeda; grant/research support from Pfizer, Bristol Meyers Squibb, Galapagos Alfasigma, and Janssen ZM - speaker fee from Friso – Friesland Campina, Galapagos, Eli Lilly, and Takeda (paid to host institution); ; advisory board fees from Johnson & Johnson, Eli Lilly, Pfizer (paid to host institution); grants from ZonMw, Niels Stensen Fellowship, MLDS, Top consortium for Knowledge and Innovation (TKI), and Galapagos

Introduction

For patients with Crohn’s disease (CD), endoscopic healing is an important long-term treatment goal per STRIDE-II consensus recommendations.¹ In this post hoc analysis, the relationships between endoscopic healing and long-term clinical outcomes were assessed in risankizumab (RZB)-treated patients with moderate to severe CD who previously failed tumor necrosis factor antagonist therapy from the phase 3 SEQUENCE trial.²

Aims & Methods

This analysis included RZB-treated patients who completed the week 48 visit in Part 1 of SEQUENCE (NCT04524611) and continued to receive RZB maintenance therapy during Part 2 of the trial. Part 2 is an ongoing open-label extension (OLE) wherein patients who received RZB induction and maintenance treatment during Part 1 could continue to receive RZB (subcutaneous 360mg every 8 weeks up to an additional 220 weeks). All patients in this post hoc analysis completed 100 weeks of RZB treatment (48 weeks in Part 1 and 52 weeks in Part 2). The proportion of patients who achieved week 100 (Part 2) clinical outcomes (including CD activity index [CDAI] response and remission, steroid-free CDAI clinical remission, and normalized fecal calprotectin [FCP] levels) were compared based on week 48 achievement of endoscopic response vs not, endoscopic remission vs not, and steroid-free endoscopic remission vs not (endpoint definitions in Table footnote), using chi-square testing. Patients with missing outcomes were imputed as nonresponders. Endoscopies were scored by a central reviewer. Long-term safety assessments for RZB have been reported elsewhere.³

Results

Of the 224 patients included in the analysis, 114 (50.9%), 80 (35.7%), and 80 (35.7%) patients achieved week 48 endoscopic response, endoscopic remission, and steroid-free endoscopic remission, respectively. A significantly greater proportion of patients who achieved week 48 endoscopic response also achieved week 100 CDAI remission and response, steroid-free CDAI clinical remission, and normalized FCP levels compared to patients who did not achieve week 48 endoscopic response (P≤.05 for all comparisons) (Table). Similar results were observed for patients who achieved week 48 endoscopic remission or steroid-free endoscopic remission (P≤.05 for all endpoints except for CDAI clinical response).

Conclusion

Results from this post hoc analysis of data from SEQUENCE demonstrated that achieving week 48 endoscopic outcomes was associated with sustained clinical improvements after 2 years of RZB treatment.

References

1. Turner D, et al. Gastroenterology. 2021 Apr;160(5):1570–83.
2. Peyrin-Biroulet L, et al. N Engl J Med. 2024 Jul 18;391(3):213–23.
3. Peyrin-Biroulet L, et al. J Crohns Colitis. 2025 Jan 22;19(Supplement_1):i1405–7.

Disclosure

Disclosures
Vipul Jairath has received has received consulting/advisory board fees from AbbVie, Alimentiv Inc, Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, 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, Ventyx, and Vividion; and speaker’s fees from, AbbVie, Ferring, Galapagos, Janssen Pfizer Shire, Takeda, and Fresenius Kabi.
Christopher Ma has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Pendopharm, Pfizer, Prometheus Biosciences Inc., Roche, Sanofi, Takeda, Tillotts Pharma; speaker's fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Eli Lilly, Ferring, Fresenius Kabi, Janssen, Organon, Pendopharm, Pfizer, Sanofi, Takeda, Tillotts Pharma; royalties from Springer Publishing; research support from AbbVie, Ferring, Pfizer.
Peter Bossuyt received financial support for research from AbbVie, Amgen, Celltrion, Mylan, Pfizer, and Takeda; lecture fees from AbbVie, Celltrion, Janssen, Lilly, and Takeda; and advisory board fees from AbbVie, Arena Pharmaceuticals, BMS, Celltrion, Dr Falk, Galapagos, Janssen, Lilly, Pentax, PSI-CRO, Roche, Takeda, and Tetrameros.
Brian G Feagan has served as a consultant or received speaker’s fees from Abbott/AbbVie, ActoGeniX, Akros, Albireo Pharma, Amgen, AstraZeneca, Avaxia Biologics, Avir Pharma, Axcan, Baxter Healthcare, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, enGene, Ferring Pharmaceuticals, gIcare Pharma, Gilead, Given Imaging, GSK, Ironwood Pharmaceuticals, Janssen Biotech (Centocor), Johnson & Johnson/Janssen, Kyowa Hakko Kirin Co, Lexicon, Lilly, Lycera, Merck, Mesoblast, Millennium, Nektar, Nestlé, Novartis, Novo Nordisk, Pfizer, Prometheus Therapeutics and Diagnostics, Protagonist Therapeutics, Receptos, Roche/Genentech, Salix Pharmaceuticals, Serono, Shire, Sigmoid Pharma, Synergy Pharmaceuticals, Takeda, Teva Pharmaceuticals, TiGenix, Tillotts, UCB, Vertex Pharmaceuticals, VHsquared, Warner Chilcott, Wyeth, Zealand Pharma, and Zyngenia, and has received research support from Abbott/AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Janssen Biotech (Centocor), Johnson & Johnson/Janssen, Millennium, Pfizer, Receptos, Roche/Genentech, Sanofi, Santarus, Tillotts, and UCB.
Namita Joshi, Nidhi Shukla, Kristina Kligys, Javier Zambrano, Toni Anschutz, and Brooke Kim are full-time employees/contractor of AbbVie and may own AbbVie stock or options.

Acknowledgments
AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the abstract. All authors had access to relevant data and participated in the drafting, review, and approval of this abstract. No honoraria or payments were made for authorship. AbbVie and authors thank all the trial investigators and the patients who participated in this clinical trial.
Medical writing support was provided by Stephanie Parsons, PhD, an employee of AbbVie. Editorial support was provided by Amy Kuang, an employee of AbbVie.

Introduction

Endoscopic healing is an important treatment goal for patients (pts) with Crohn’s disease (CD).¹ Herein, the relationships between endoscopic healing and achievement of long-term patient reported outcomes (PROs) and occurrence of CD-related hospitalization were assessed in pts with moderate to severe CD treated with risankizumab (RZB) maintenance therapy from the FORTIFY trial.

Aims & Methods

In FORTIFY, pts who had clinical response to RZB induction² received 52 weeks (wks) of maintenance therapy (subcutaneous 180mg or 360mg every 8wks) in substudy 1³ and continued receiving RZB as per their treatment assignment in the open-label extension (OLE) substudy 3. This analysis included pts who completed 2 years (y) of RZB in the OLE (cumulative RZB treatment of 3 years including 52wks in substudy 1) (cutoff date: 01MAR2024). Clinically meaningful improvements in PROs were assessed, including Inflammatory Bowel Disease Questionnaire (IBDQ) response (≥16-point increase in total score), IBDQ remission (total score ≥170-points), improvement in 36-Item Short Survey (SF-36) physical component score (PCS, ≥4.1-points) and mental component summary (MCS, ≥3.9-points), EuroQol-5D questionnaire visual analog scale (EQ-5D-5L VAS; ≥9.2-points), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) response (≥9-points). Exposure-adjusted occurrence of CD-related hospitalizations was also assessed as incidence rates (events/100 patient-y) from OLE wk52 to wk152. The proportion of pts who achieved each outcome at wk152 were compared based on their achievement of wk52 endoscopic response, endoscopic remission, or ulcer-free endoscopy vs not (endpoint definitions in Table footnote) using chi-square testing. Pts with missing outcomes were considered nonresponders. Endoscopies were scored by a central reviewer. Long-term safety of RZB has been reported.²

Results

Of the 257 pts included in the analysis, 134 (52.1%), 99 (38.5%), and 79 (30.7%) pts achieved wk52 endoscopic response, endoscopic remission, and ulcer-free endoscopy, respectively. Significantly more pts who achieved wk52 endoscopic response also achieved IBDQ response and remission, SF36 PCS and MCS response, and improvement in FACIT-F and EQ-5D-5L VAS scores at wk152 (P≤.0001 for all comparisons) vs pts who did not achieve wk52 endoscopic response (Table). Similar results were observed for pts who achieved wk52 endoscopic remission (P≤.01) and pts who achieved wk52 ulcer-free endoscopy (P≤.02, except for SF36 MCS response) at wk152. CD-related hospitalizations from wk56 to wk152 were significantly lower for pts who achieved wk52 endoscopic remission and endoscopic response and numerically lower for pts who achieved wk52 ulcer-free endoscopy, vs not.

Conclusion

A significantly greater proportion of pts achieved 3y sustained improvement in PROs when they achieved endoscopic outcomes at 52wks of RZB maintenance treatment. Achievement of endoscopic outcomes at 52wks also resulted in fewer CD-related hospitalizations through 152wks when continuing active therapy, pointing to favorable long-term outcomes of disease.

References

Turner D, et al. Gastroenterology. 2021;160:1570-83.
Ferrante M, et al. J Crohns Colitis. 2021; 15(12):2001-2010.

Disclosure

Christopher Ma has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Pendopharm, Pfizer, Prometheus Biosciences Inc., Roche, Sanofi, Takeda, Tillotts Pharma; speaker's fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Eli Lilly, Ferring, Fresenius Kabi, Janssen, Organon, Pendopharm, Pfizer, Sanofi, Takeda, Tillotts Pharma; royalties from Springer Publishing; research support from AbbVie, Ferring, Pfizer.
Brian G Feagan has served as a consultant or received speaker’s fees from Abbott/AbbVie, ActoGeniX, Akros, Albireo Pharma, Amgen, AstraZeneca, Avaxia Biologics, Avir Pharma, Axcan, Baxter Healthcare, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, enGene, Ferring Pharmaceuticals, gIcare Pharma, Gilead, Given Imaging, GSK, Ironwood Pharmaceuticals, Janssen Biotech (Centocor), Johnson & Johnson/Janssen, Kyowa Hakko Kirin Co, Lexicon, Lilly, Lycera, Merck, Mesoblast, Millennium, Nektar, Nestlé, Novartis, Novo Nordisk, Pfizer, Prometheus Therapeutics and Diagnostics, Protagonist Therapeutics, Receptos, Roche/Genentech, Salix Pharmaceuticals, Serono, Shire, Sigmoid Pharma, Synergy Pharmaceuticals, Takeda, Teva Pharmaceuticals, TiGenix, Tillotts, UCB, Vertex Pharmaceuticals, VHsquared, Warner Chilcott, Wyeth, Zealand Pharma, and Zyngenia, and has received research support from Abbott/AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Janssen Biotech (Centocor), Johnson & Johnson/Janssen, Millennium, Pfizer, Receptos, Roche/Genentech, Sanofi, Santarus, Tillotts, and UCB.
Peter Bossuyt received financial support for research from AbbVie, Amgen, Celltrion, Mylan, Pfizer, and Takeda; lecture fees from AbbVie, Celltrion, Janssen, Lilly, and Takeda; and advisory board fees from AbbVie, Arena Pharmaceuticals, BMS, Celltrion, Dr Falk, Galapagos, Janssen, Lilly, Pentax, PSI-CRO, Roche, Takeda, and Tetrameros.
Vipul Jairath has received has received consulting/advisory board fees from AbbVie, Alimentiv Inc, Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, 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, Ventyx, and Vividion; and speaker’s fees from, AbbVie, Ferring, Galapagos, Janssen Pfizer Shire, Takeda, and Fresenius Kabi.
Namita Joshi, Nidhi Shukla, Kristina Kligys, Ari Stromberg,andJameson Crowley are full-time employees/contractor of AbbVie and may own AbbVie stock or options.
Acknowledgments
AbbVie funded this study (NCT03105102) and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the abstract. All authors had access to relevant data and participated in the drafting, review, and approval of this abstract. No honoraria or payments were made for authorship. AbbVie and authors thank all the trial investigators and the patients who participated in this clinical trial.
Medical writing support was provided by Stephanie Parsons, PhD, an employee of AbbVie. Editorial support was provided by Amy Kuang, an employee of AbbVie.

Introduction

Superior Mesenteric Artery Syndrome (SMAS), also known as Wilkie’s syndrome, is a rare gastrointestinal condition characterized by compression of the distal duodenum between the abdominal aorta (AA) and the superior mesenteric artery (SMA). Evidence on Wilkie’s syndrome is limited, reviews are based on small cohorts and case studies^1-3. Patients with SMAS typically present with postprandial epigastric discomfort, nausea, vomiting, stomach distention, and reflux, leading to malnutrition and weight loss. As mesenteric fat decreases due to the weight loss, the duodenal obstruction worsens, increasing SMAS symptoms. SMAS mostly affects young females aged 20-30 years and is challenging to diagnose due its overlap with dyspepsia, anorexia nervosa and median arcuate ligament syndrome^1-3. SMAS can present acutely, after weight loss from bariatric surgery, malnutrition or (hyper)metabolic disorders. It also presents chronically, due to an anatomically high duodenal position or a low aortic SMA origin^1-3. Diagnostic imaging, including computed tomography (CT) typically reveals a reduced SMA-AA angle <25° and a characteristic vertical, abrupt duodenal obstruction on barium X-ray series^1,2. Conservative treatment focuses on improving gastrointestinal motility and increasing the SMA-AA angle by weight gain to regain mesenteric fat¹. If conservative treatment fails, surgical intervention is considered, with duodenojejunostomy being most commonly performed. Yet, this carries potential severe complications such as anastomotic leakage and non-physiological gastro-duodenal changes. Recent evidence suggests laparoscopic Treitz ligament release may offer a viable and low-risk alternative^3,4.

Aims & Methods

This study aims to introduce a standardized, low risk treatment protocol for SMAS. The protocol includes: 1) Jejunal tube feeding for six-eight weeks, 2) Laparoscopic release of the Treitz ligament, and 3) SMA reimplantation⁵. The protocol was implemented at three hospitals in the Netherlands, Medisch Spectrum Twente, Franciscus, and Erasmus MC.

Results

A total of 12 patients were treated according to this protocol from 2020 until 2024. The cohort consisted of 7 (58.3%) female patients, with a mean age of 29.2 years (SD 11.8). The average weight and body mass index were 60.33 kg (SD 6.5) and 20.01 (SD 3.4). The mean SMA-AA angle measured on CT scans was 22.55° (SD 13.1). All patients started treatment with jejunal feeding. Nine patients underwent laparoscopic Treitz ligament release, with 7 experiencing complete resolution of symptoms. One patient with co-existing Nutcracker syndrome received primary SMA infra-renal reimplantation, with complete symptom release after the surgery. In two patients, symptoms persisted following Treitz ligament release, resembling gastroparesis and irritable bowel syndrome. The 2 remaining patients are planned for laparoscopic Treitz ligament release.

Conclusion

The combination of jejunal feeding followed by laparoscopic Treitz ligament release, represents a safe and effective treatment approach for SMAS; 7/9 patients who underwent the Treitz ligament release experienced resolution of all symptoms, demonstrating the efficacy of protocol. This approach offers an alternative to traditional surgical procedures, such as duodenojejunostomy, and reduces the risks of substantial short- and long-term complications. Further research with larger sample sizes is required to confirm the long-term outcomes and advantages of this protocol compared to other treatment strategies for SMAS.

References

1. Oka A, Awoniyi M, Hasegawa N, Yoshida Y, Tobita H, Ishimura N, Ishihara S. Superior mesenteric artery syndrome: Diagnosis and management. World J Clin Cases. 2023 May 26;11(15):3369-3384. doi: 10.12998/wjcc.v11.i15.3369. PMID: 37383896;
2. Navandhar PS, Shinde RK, Gharde P, Nagtode T, Badwaik N. Understanding Superior Mesenteric Artery Syndrome: Etiology, Symptoms, Diagnosis, and Management. Cureus. 2024 Jun 2;16(6):e61532. doi: 10.7759/cureus.61532. PMID: 38957238; PMCID: PMC11218894
3. Beita AKV, Whayne TF. The Superior Mesenteric Artery: From Syndrome in the Young to Vascular Atherosclerosis in the Old. Cardiovasc Hematol Agents Med Chem. 2019;17(2):74-81. doi: 10.2174/1871525717666190920100518. PMID: 31538906.
4. Fang JF, Wei B, Zheng ZH, Lei PR, Chen TF, Wei HB. Laparoscopic lysis of the ligament of treitz for superior mesenteric artery syndrome. Dig Surg. 2014;31(4-5):291-6. doi: 10.1159/000367670. Epub 2014 Oct 17. PMID: 25342434.
5. Ali T, Tomka J, Bakirli I, Bakirov I. Surgical Treatment of Wilkie's Syndrome by Vascular Transposition. Cureus. 2022 Apr 18;14(4):e24251. doi: 10.7759/cureus.24251. PMID: 35475250; PMCID: PMC9018456.
6. Pourhassan S, Grotemeyer D, Fürst G, Rudolph J, Sandmann W. Infrarenal transposition of the superior mesenteric artery: a new approach in the surgical therapy for Wilkie syndrome. J Vasc Surg. 2008 Jan;47(1):201-4. doi: 10.1016/j.jvs.2007.07.037. Epub 2007 Oct 18. PMID: 17949939

Introduction

The STRIDE-II consensus on the management of Crohn’s disease (CD) highlights the importance of achieving multiple treatment targets, including clinical remission, normalisation of the inflammatory biomarkers high-sensitivity C-reactive protein (hs-CRP) and fecal calprotectin (FCP), and quality of life (QoL) improvements.¹ In this post hoc analysis of the SEQUENCE open-label extension (OLE), we assessed inflammatory biomarker reductions and improvements in clinical and QoL outcomes (alone or in combination) in patients (pts) with moderately to severely active CD treated with risankizumab (RZB), an interleukin-23 p19 inhibitor.

Aims & Methods

In Part 2 of SEQUENCE (NCT04524611), pts randomised to the RZB arm during Part 1 and who completed the week (wk) 48 visit were eligible to continue receiving open-label 360mg subcutaneous RZB maintenance dose every 8 wks.² This analysis included all patients who completed wk100 of RZB treatment or who discontinued treatment prior to wk100 in Part 2 (cutoff date: July 11, 2024). Pts with elevated hs-CRP (> 5 mg/L) or FCP (> 250 mg/kg) at induction baseline were assessed for achievement of normalised hs-CRP or FCP alone or in combination with clinical remission per CD activity index (CDAI) or per stool frequency/abdominal pain score (SF/APS), or with inflammatory bowel disease questionnaire (IBDQ) remission (endpoints defined in Table footnote) at wks 52 (OLE baseline), 76, and 100. Data were assessed for all intent-to-treat pts using as observed (AO) regardless of rescue therapy and nonresponder imputation (NRI). Safety was previously reported and not assessed in this post hoc analysis.³

Results

Of the 224 pts who entered SEQUENCE Part 2, 184 pts had elevated hs-CRP or FCP levels at induction baseline and were included in this analysis. The majority of these pts achieved normalisation of hs-CRP or FCP (per AO data) at wk52 (77.7%) and continued to show improvement at wks 76 and 100 (83.9% and 86.6%, respectively) (Table). Most of these pts also achieved both normalised hs-CRP or FCP and clinical remission simultaneously at wks 52, 76, and 100 per CDAI (AO data: 60.9%, 66.2%, and 71.0%, respectively) and per SF/APS (AO data: 55.2%, 60.2%, and 62.9%, respectively). The proportion of pts who achieved normalisation of hs-CRP or FCP and IBDQ remission increased from wk52 through wk100 (AO data; wk52: 50.0%, wk76: 54.9%, wk100: 57.1%). NRI data for all endpoints are summarized in the Table.

Conclusion

In this post hoc analysis, pts with moderately to severely active CD demonstrated inflammatory biomarker normalisation with RZB treatment and continued improvement of inflammation up to wk100 in the SEQUENCE OLE. Notably, most pts simultaneously achieved normalisation of inflammatory biomarkers plus clinical or QoL outcomes through wk100 of RZB treatment.

References

1. Turner D, et al. Gastroenterology. 2021;160:1570–83.
2. Peyrin-Biroulet L, et al. N Engl J Med. 2024;391:213–23.
3. L Peyrin-Biroulet, et al. Journal of Crohn's and Colitis. 2025;19(Supplement_1):i1405–07.

Disclosure

Benjamin L. Cohen has received advisory board and consultancy fees from AbbVie, ALPCO, Celgene-Bristol Myers Squibb, Johnson & Johnson Innovative Medicine, Lilly, Pfizer, Sublimity Therapeutics, Takeda, TARGET RWE; DSMB: Emmes Biopharma Services LLC; speakers’ fees from AbbVie and Takeda.
Corey Siegel has served as a consultant for AbbVie, BMS, Boomerang, Buhlmann, Celltrion, Johnson & Johnson, Lilly, Napo Pharmaceuticals, Path Healthcare, Pfizer, Prometheus Biosciences & Labs, Sanofi, Takeda, and Trellus Health; received grants from AbbVie, Johson & Johnson, Pfizer, and Takeda; and is co-founder of MiTest Health, LLC, technology “System and Method of Communicating Predicted Medical Outcomes” licensed to Takeda; equity interest in Path Healthcare and Trellus Health
Alessandro Armuzzi has received consulting/advisory board fees from AbbVie, Alfa Sigma, Amgen, Arena, Biogen, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Mylan, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sandoz, Takeda, and Teva Pharmaceuticals; speaker’s fees from AbbVie, Alfa Sigma, Amgen, Arena, Biogen, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, and Teva Pharmaceuticals; and research support from MSD, Takeda, Pfizer, and Biogen.
Fernando Aponte, Toni Anschutz, Andrew Garrison, Namita Joshi, and Javier Zambrano are full-time employees of AbbVie and may own AbbVie stock or stock options.
Laurent Peyrin-Biroulet has received personal fees from AbbVie, Adacyte, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena, Biogen, BMS, Celltrion, CONNECT Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, HAC-Pharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Nordic Pharma, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par’Immune, Pfizer, Prometheus, Protagonist, Roche, Sanofi, Sandoz, Takeda, Theravance, Thermo Fisher, Tigenix, Tillots, Viatris, Vifor, Ysopia, Abivax, Samsung, Ventyx, Roivant, and Vectivbio.

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.

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).

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.