Introduction
Risankizumab (RZB) is an interleukin [IL]-23 p19 inhibitor approved for the treatment of Crohn’s disease (CD). In the SEQUENCE head-to-head trial in patients with moderately to severely active CD, RZB was more effective in achieving endoscopic outcomes over ustekinumab (UST; IL-12/IL-23 p40 inhibitor),1 with higher rates of endoscopic remission, regardless of CD location, observed in post hoc analyses.2-3 Here, we evaluate the changes from baseline in Simple Endoscopic Score for Crohn’s Disease (SES-CD) total score and SES‑CD components at weeks 24 and 48.
Aims & Methods
SEQUENCE was an open-label, multicenter, randomized, efficacy assessment–blinded study in adults with moderately to severely active CD who had experienced inadequate response to ≥ 1 anti-tumor necrosis factor (TNF) therapy. Patients in the primary efficacy analysis set were randomized 1:1 to receive RZB (intravenous [IV] 600 mg induction dose at weeks 0, 4, and 8, followed by a subcutaneous [SC] 360 mg maintenance dose every 8 weeks starting at week 12) or UST (single weight-based IV induction dose, followed by a SC 90 mg maintenance dose every 8 weeks starting at week 8) up to week 48. A mandatory corticosteroid taper started at week 2. In this post hoc analysis, the mean changes from baseline in total SES-CD score and individual SES-CD components (affected surface, ulcerated surface, size of ulcers, and presence of narrowing) at weeks 24 and 48 were evaluated. Data include patients with nonmissing values at both baseline and the corresponding visit; all P values are nominal.
Results
Of 520 enrolled patients (RZB, 255; UST, 265), evaluable endoscopy data were available at week 24 for 461 patients (RZB, 238; UST, 223) and at week 48 for 379 patients (RZB, 210; UST, 169). Baseline SES-CD scores were generally similar between treatment groups (Table). At week 24, treatment with RZB resulted in greater improvement in total SES‑CD from baseline compared with UST (−6.6 vs −3.9; nominal P < .0001), and similarly, improvements at week 48 were greater with RZB vs UST (−7.3 vs −4.8; nominal P = .0006). Further, numerically greater improvements were observed with RZB vs UST across all individual SES-CD components at weeks 24 and 48, with notable differences between RZB and UST seen in the individual SES-CD components of affected surface, ulcerated surface, and size of ulcers (nominal P < .01).
| Table. Total SES-CD and Individual SES-CD Components Over Time |
| Parameter, mean (SD) | Baselinea | Change From Baseline at Week 24a | Change From Baseline at Week 48b |
RZB
(n = 238) | UST
(n = 223) | RZB
(n = 238) | UST
(n = 223) | RZB
(n = 210) | UST
(n = 169) |
| Total SES-CD | 13.4 (7.1) | 13.8 (7.2) | −6.6 (7.4)*** | −3.9 (6.4) | −7.3 (7.4)*** | −4.8 (6.8) |
| SES-CD components | | | | | | |
| Affected surface | 4.7 (2.9) | 5.0 (3.3) | −2.5 (2.9)*** | −1.5 (3.0) | −2.6 (3.0)** | −1.8 (3.1) |
| Ulcerated surface | 3.6 (2.4) | 3.7 (2.3) | −1.9 (2.4)*** | −1.2 (2.0) | −2.1 (2.4)** | −1.4 (2.2) |
| Size of ulcers | 4.3 (2.5) | 4.4 (2.5) | −2.2 (2.7)*** | −1.4 (2.2) | −2.5 (2.7)*** | −1.7 (2.1) |
| Presence of narrowing | 0.8 (1.3) | 0.7 (1.2) | −0.1 (1.3) | 0.1 (1.1) | −0.1 (1.2) | 0.1 (1.1) |
RZB, risankizumab; SES-CD, Simple Endoscopic Score for Crohn’s Disease; UST, ustekinumab.
**Nominal P < .01; ***nominal P < .001 vs UST based on Student’s t test.
aValues only include patients with nonmissing values at both baseline and week 24.
bValues only include patients with nonmissing values at both baseline and week 48. Patients discontinuing the study before week 24 or 48 were not included in the analysis for that respective timepoint. |
Conclusion
In this head-to-head study, RZB was more effective than UST in improving endoscopic disease activity per SES-CD scores in patients with CD who had experienced inadequate response to anti-TNF therapy. Differences were observed both at weeks 24 and 48 and were driven by SES-CD components of the size of ulcers, ulcerated surface, and affected surface.
References
- Peyrin-Biroulet L, et al. United European Gastroenterol J. 2023;11:919−922. Abstract LB01.
- Peyrin-Biroulet L, et al. J Crohns Colitis. 2024;18:i90−i91. Abstract DOP10.
- Peyrin-Biroulet L, et al. J Crohns Colitis. 2024;18:i104−i105. Abstract DOP18.
Disclosure
PMI has received speaking fees, research grants, and/or advisory fees from AbbVie, Arena, Boehringer Ingelheim, BMS, Celgene, Celltrion, Dr Falk, Ferring, Galapagos, Genentech, Gilead, Hospira, Janssen, Lilly, MSD, Pfizer, Pharmacosmos, Prometheus, Roche, Samsung Bioepis, Sandoz, Sapphire, Shire, Takeda, Tillotts, Topivert, VH2, Vifor, and Warner Chilcott.
J-FC has been a consultant or advisory board member for AbbVie, Amgen, Boehringer Ingelheim, Arena, Celgene, Celltrion, Enterome, Ferring, Genentech, Gilead, J&J, Lilly, Medimmune, Merck, Nextbiotix, Novartis, Otsuka, Pfizer, Protagonist, Second Genome, Seres, Shire, Takeda, and Theradiag. He is a speaker for AbbVie, Celgene, Ferring, and Takeda; holds stock options for Intestinal Biotech Development, and GENFIT; and has received research grants from AbbVie, J&J, and Takeda.
GD’H has been an advisor for AbbVie, Ablynx, Active Biotech AB, Agomab, Alimentiv, Allergan, Alphabiomics, Amakem, Amgen, AM, Applied Molecular Therapeutics, Arena, AstraZeneca, Biogen, BMS, Boehringer Ingelheim, Celltrion, DSM, Echo, Engene, Exeliom, Dr Falk, Ferring, Galapagos, Genentech/Roche, Gilead, GSK, Gossamerbio, Immunic, J&J, Kintai, Lilly, Lument, Lycera, Medtronic, MSD, Mitsubishi Tanabe, Novo Nordisk, Otsuka, Pfizer, Photopill, ProciseDx, Prodigest, Progenity, Prometheus laboratories/Nestlé, Protagonist, RedHill, Samsung Bioepis, Sandoz, Seres, Setpoint, Shire, Takeda, Teva, Tillotts, Topivert, Versant, and Vifor.
MF has received research grants from AbbVie, Biogen, EG, Janssen, Pfizer, Takeda, and Viatris; consultancy fees from AbbVie, AgomAb, Boehringer Ingelheim, Celgene, Celltrion, Janssen-Cilag, Lilly, MRM Health, MSD, Pfizer, Takeda, and ThermoFisher; and speakers’ fees from AbbVie, Biogen, Boehringer Ingelheim, Dr Falk, Ferring, Janssen-Cilag, MSD, Pfizer, Takeda, Truvion, and Viatris.
FC has received consulting fees from AbbVie, Biogen, BMS, Celgene, Ferring, Galapagos, Gilead, Janssen, Lilly, Lionhealth, MSD, Mundipharma, Pfizer, Roche, and Takeda; lecture fees from AbbVie, Allergy Therapeutics, Biogen, Ferring, Janssen, Pfizer, and Takeda; and unrestricted research grants from AbbVie, Giuliani, MSD, Sofar, and Takeda.
BS has received consulting fees from AbbVie, Abivax, Arena, Boehringer Ingelheim, BMS, Celgene, Dr Falk, Endpoint Health, Galapagos, Gilead, Janssen, Lilly, Pfizer, Prometheus, and Takeda, and speaker’s fees from AbbVie, BMS, CED Service, Dr Falk, Ferring, Galapagos, Janssen, Lilly, Novartis, Pfizer, and Takeda.
SvH, BK, TA, and AG are full-time employees of AbbVie and may own AbbVie stock or stock options.
LP-B has received personal fees from AbbVie, Abivax, Adacyte, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena, Biogen, BMS, Celltrion, CONNECT Biopharm, Cytoki, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, HAC-Pharma, IAG Image Analysis, Index, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Nordic, Novartis, OM, ONO, OSE Immunotherapeutics, Pandion, Par’Immune, Pfizer, Prometheus, Protagonist, Roche, Roivant, Samsung, Sanofi, Sandoz, Takeda, Theravance, Thermo Fisher, Tigenix, Tillots, VectivBio, Ventyx, Viatris, Vifor, and Ysopia.