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).
Clinical Outcomes at Week 100 (Week 52 of SEQUENCE OLE)
n/N (%)
| Week 48 Endoscopic responsea (Yes)
| Week 48 Endoscopic responsea
(No)
| P
value
| Week 48 Endoscopic remissionb (Yes)
| Week 48 Endoscopic remissionb (No)
| P
value
| Week 48
Steroid-Free Endoscopic remissionc
(Yes)
| Week 48
Steroid-Free Endoscopic remissionc
(No)
| P
value |
CDAI clinical responsed
CDAI clinical remissione
Steroid-free CDAI clinical remissionf
Normalized FCPg
| 80/114 (70.2)
77/114
(67.5)
77/114
(67.5)
67/114
(58.8)
| 61/110
(55.5)
57/110
(51.8)
57/110
(51.8)
49/110
(44.5)
| .0226
.0164
.0164
.0332
| 57/80
(71.3)
55/80
(68.8)
55/80
(68.8)
54/80
(67.5)
| 84/144
(58.3)
79/144
(54.9)
79/144
(54.9)
62/144
(43.1)
| .0551
.0422
.0422
.0005
| 57/80
(71.3)
55/80
(68.8)
55/80
(68.8)
54/80
(67.5)
| 84/144
(58.3)
79/144
(54.9)
79/144
(54.9)
62/144
(43.1)
| .0551
.0422
.0422
.0005
|
Abbreviations: BL, baseline; CD, Crohn’s disease; CDAI, CD activity index; FCP, fecal calprotectin; OLE, open-label extension.
aEndoscopic response: decrease in the SES-CD > 50% from induction BL (or for patients with isolated ileal disease and a BL SES-CD = 4, ≥ 2-point reduction from induction BL).
bEndoscopic remission: SES-CD ≤ 4, ≥ 2-point reduction from BL, and no subscore >1 in any individual variable.
cSteroid-free endoscopic remission: not receiving corticosteroids at the corresponding visit and in endoscopic remission.
dCDAI clinical response: reduction of CDAI ≥ 100 points from induction BL.
eCDAI clinical remission: CDAI < 150.
fSteroid-free CDAI clinical remission: not receiving corticosteroids at the corresponding visit and in clinical remission.
gNormalized FCP: ≤ 250 mcg/g.
Bold font denotes a P value ≤ .05. |
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.
