Introduction

The efficacy and safety of risankizumab (RZB), an anti-interleukin 23p19 monoclonal antibody, as induction and maintenance therapy for adults with moderately to severely active ulcerative colitis (UC) was recently reported.^1,2 Influences of baseline disease characteristics on clinical outcomes are important to consider when optimizing UC treatment. Herein we analyze the efficacy of RZB stratified by baseline UC disease characteristics.

Aims & Methods

In the 12-week phase 3 INSPIRE induction study (NCT03398148) patients with moderately to severely active UC were randomized 2:1 to receive intravenous (IV) RZB 1200 mg or placebo (PBO) at weeks 0, 4, and 8. Patients with clinical response to RZB IV induction at week 12 or 24 in the phase 2b/3 induction studies were randomized 1:1:1 to receive subcutaneous (SC) RZB 180 mg, RZB 360 mg, or PBO (RZB withdrawal) every 8 weeks in the 52-week phase 3 COMMAND maintenance study (NCT03398135). This post hoc analysis evaluates clinical response, clinical remission, endoscopic remission, endoscopic improvement, and histological-endoscopic mucosal improvement (HEMI) at week 12 and 52 in subgroups stratified by baseline disease characteristics (Adapted Mayo score, pancolitis, high‑sensitivity C‑reactive protein [hs‑CRP], Mayo endoscopic subscore [ES], and disease duration).

Results

The induction analysis included 650 and 325 patients who received RZB 1200 mg IV and PBO IV, respectively. The maintenance analysis included 179, 186, and 183 patients who received RZB 180 mg SC, RZB 360 mg SC, and PBO (RZB withdrawal) SC, respectively. At induction week 12, the proportions of patients receiving RZB 1200 mg IV who achieved clinical response were numerically higher for the following baseline characteristic subgroups: pancolitis absence (70.5%) vs pancolitis presence (58.4%), Mayo ES of 2 (75.5%) vs Mayo ES of 3 (59.0%), and hs-CRP ≤ 5 mg/mL (68.9%) vs hs-CRP > 5 mg/mL (57.3%); the proportions of patients receiving RZB 1200 mg IV who achieved clinical remission at induction week 12 were also numerically higher for subgroups with pancolitis absence (25.3%) vs pancolitis presence (15.6%), Mayo ES of 2 (31.7%) vs Mayo ES of 3 (14.9%), and hs-CRP ≤ 5 mg/mL (23.7%) vs hs-CRP > 5 mg/mL (14.5%; Table). Differences in outcomes were not observed between subgroups stratified by Adapted Mayo score or disease duration. At week 52 of the maintenance study, there was no impact of baseline disease characteristics on achievement of clinical response and clinical remission with RZB (Table).

Conclusion

RZB induction and maintenance therapy improved clinical outcomes, regardless of baseline disease characteristics. Numerically higher RZB induction efficacy was observed for patients with no baseline pancolitis, Mayo ES of 2, and hs‑CRP ≤ 5 mg/L. These trends are consistent with prior observations that patients with milder UC disease phenotypes tend to be more responsive to therapy.

References

1. Louis E, et al. United Eur Gastroenterol J . 2023;11(S8):26–28. Abstract OP021.
2. Louis E, et al. J Crohns Colitis. 2024;18(S1):i10–12. Abstract OP06.

Disclosure

CH has served as a consultant, advisor, and/or has received education funds from AbbVie, Bausch Health, BMS, the Helmsley Charitable Trust, Janssen, Pfizer, Roivant, and Takeda.
MDL has received consulting fees and/or research grants from AbbVie, BMS, Intercept, Janssen, Lilly, Pfizer, Prometheus, Takeda, and Target RWE.
SRF has served as a consultant or advisor for AbbVie, Janssen, MSD, Takeda, Tillots, and Vitoria.
TF has received research grants and/or speaking honoraria from AbbVie, Ajinomoto, Alfresa, BI, BMS, Celgene, Celltrion, Daiichi Sankyo, EA Pharma, Eisai, Gilead, Janssen, Kissei, Kyorin, Kyowa Hakko Kirin, Lilly, Mebix, Mitsubishi Tanabe, Mochida, Nichiiko, Nippon Kayaku, Pfizer, Sanofi, Taiho, Takeda, and Zeria.
ZR has no disclosures to report.
JK, PL, SC, LC, RV, and PMH are employees of AbbVie and may hold AbbVie stock and/or stock options.
FA-A has served as a consultant and/or has received grants and speaker fees from AbbVie, Celltrion, Kern, MSD, and Takeda.
RA has served as a consultant or advisor for AbbVie, AstraZeneca, BI, Biogen, BMS, CED-Service GmbH, Celltrion, Falk Foundation, Galapagos, Gilead, InDex, Janssen-Cilag, Lilly, MSD, Roche, and Takeda.
Funding
AbbVie funded this study and participated in the study design, research, data collection, analysis, 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 the authors thank all trial investigators and the patients who participated in this clinical trial. Medical writing support was provided by Morgan A Gingerich, PhD, of JB Ashtin, and funded by AbbVie, and Karen Chien, PhD, of AbbVie.