Introduction
Risankizumab (RZB), a selective interleukin-23 p19 inhibitor approved for moderate-to-severe Crohn’s disease (CD), has shown sustained efficacy and a consistent safety profile for up to 4 years (yrs) of treatment in the FORTIFY open-label extension (OLE) study.1,2 In some patients (pts) inadequate response (IR) occurs, particularly in those with prior exposure to advanced therapies. Here, we evaluated the long-term efficacy and safety of RZB rescue therapy among pts who experienced IR to RZB in the FORTIFY OLE.
Aims & Methods
Pts who completed 52 weeks (wks) of double-blind randomised maintenance treatment in FORTIFY (NCT03105102) enrolled in the OLE. Pts received 180 mg subcutaneous (SC) RZB every 8 wks (Q8w), starting at wk 56, except for pts who previously received rescue therapy (1 dose of 1200 mg IV followed by 360 mg SC) due to IR; these pts received 360 mg SC Q8w in the OLE. IR was defined as increased clinical symptoms plus an objective marker of inflammation (details in Table footnote). In the OLE, pts with IR could receive up to 2 rescue doses per yr, ≥ 16 wks apart, and up to 3 total rescue doses. All pts who received ≥ 1 dose of RZB rescue therapy during the OLE, including pts who received rescue at OLE wk 0, were included in this analysis. Efficacy was assessed at the time of rescue (wk 0 of rescue) and every 24 wks thereafter (see Table for additional details). Clinical response per CD Activity Index (CDAI), clinical remission per CDAI and per stool frequency/abdominal pain score (SF/APS), endoscopic response, and endoscopic remission were analysed as observed (AO) (definitions in Table footnote). Treatment-emergent adverse events (TEAEs) reported after the date of the first RZB rescue visit in the OLE were summarised (cutoff date: 25 November 2025).
Results
A total of 287 pts of 1148 pts (25%) who entered the FORTIFY OLE received RZB rescue therapy and were included in this analysis; among them, 229/287 (79.8%) received 1 rescue in OLE until the cutoff date, 44/287 (15.3%) received 2 rescues, and 14/287 (4.9%) received 3 rescues. Per AO data, rates of CDAI clinical response, clinical remission per CDAI, and clinical remission per SF/APS following rescue increased through post-rescue wk 48, with further increases generally observed through post-rescue wk 192, reaching rates of 94.6%, 67.6%, and 65.9%, respectively (Table). Similarly, rates of endoscopic response and endoscopic remission increased substantially between wks 0 and 48 post-rescue, and at post-rescue wk 96 were 50.0% and 34.3%, respectively. The exposure-adjusted event rates of serious TEAEs and TEAEs leading to discontinuation were low and consistent with RZB’s known AE profile (Table).1–6 The most common serious TEAE was worsening CD (4.2 E/100PYs). TThere was 1 death, which was not considered to be related to RZB treatment (see Table footnote).
Parameter
% (95% CI) n/N
| Post-Rescue Week |
0
| 24
| 48
| 72
| 96
| 120
| 144
| 168
| 192
|
CDAI
Clinical
Response
CDAI
Clinical
Remission
SF/APS
Clinical
Remission
Endoscopic
Response
Endoscopic
Remission
| 41.5
(35.9,
47.2)
119/287
14.3
(10.7,
18.8)
41/287
1
(0.4,
3.0)
3/287
26.0
(19.6,
33.6)
39/150
6.7
(3.7,
11.8)
10/150
| 74.6
(68.6,
79.7)
173/232
48.3
(41.9,
54.7)
112/232
40.5
(34.6,
46.6)
104/257
47.9
(36.9,
59.2)
35/73
30.1
(20.8,
41.4)
22/73
| 85.1
(79.0,
89.7)
143/168
59.5
(52.0,
66.7)
100/168
52.4
(45.3,
59.4)
99/189
58.8
(45.2,
71.2)
30/51
35.3
(23.6,
49.0)
18/51
| 85.1
(78.5,
90.0)
126/148
58.8
(50.7,
66.4)
87/148
48.8
(41.2,
56.4)
80/164
55.3
(41.2,
68.6)
26/47
40.4
(27.6,
54.7)
19/47
| 81.9
(74.3,
87.6)
104/127
61.4
(52.7,
69.4)
78/127
53.2
(45.0,
61.2)
75/141
50.0
(38.6,
61.4)
35/70
34.3
(24.2,
46.0)
24/70
| 85.4
(77.4,
91.0)
88/103
70.9
(61.5,
78.8)
73/103
60.0
(50.9,
68.5)
69/115
| 85.9
(76.5,
91.9)
67/78
70.5
(59.6,
79.5)
55/78
60.2
(49.8,
69.8)
53/88
| 90.9
(80.4,
96.1)
50/55
69.1
(56.0,
79.7)
38/55
57.4
(44.9,
69.0)
35/61
| 94.6
(82.3,
98.5)
35/37
67.6
(51.5,
80.4)
25/37
65.9
(50.5,
78.4)
27/41
|
Exposure-adjusted event rate (E/100PYs) at week 192 of rescue
| On/After Rescue for Rescued Patients
(N = 287)
(PYs = 618.6)
| Prior to Rescue for All Patients
(N = 1112)
(PYs = 3411.8) |
Any AE
AEs related to
study drug according
to the investigator
Serious AEs
AEs leading to discontinuation
of study drug
AEs leading to deatha
| 1287 (208.0)
123 (19.9)
118 (19.1)
28 (4.5)
1 (0.2)
| 5372 (157.5)
648 (19.0)
406 (11.9)
52 (1.5)
3 (< 0.1)
|
AE, adverse event; AO, as observed; AP, abdominal pain; APS, abdominal pain score; BL, baseline; CD, Crohn's disease; CDAI, Crohn’s Disease Activity Index; FCP, faecal calprotectin; hs-CRP, high-sensitivity C-reactive protein; IR, inadequate response; IV, intravenous; mNRI, modified nonresponder imputation; RZB, risankizumab; SC, subcutaneous; SES-CD, Simple Endoscopic Score for Crohn’s Disease; SF, stool frequency; TEAE, treatment-emergent adverse event
CDAI clinical response: reduction of CDAI ≥ 100 points from BL of the induction study; CDAI clinical remission: CDAI < 150; SF/APS clinical remission: average daily SF ≤ 2.8 and not worse than BL of induction and average daily APS ≤ 1 and not worse than BL of induction. Endoscopic response is defined as decrease in SES-CD > 50% from BL of the induction study (or for subjects with isolated ileal disease and a BL SES-CD = 4, ≥ a 2-point reduction from BL of the induction study). Endoscopic remission is defined as SES-CD ≤ 4 and at least a 2-point reduction versus BL of the induction study and no subscore > 1 in any individual variable.
IR was defined as an average daily SF ≥ 3.3 and/or average daily AP score ≥ 1.5 confirmed by an objective marker of inflammation (hs-CRP ≥ 5 mg/L and/or FCP ≥ 250 µg/g, or if hs-CRP and/or FCP are not elevated, SES-CD, excluding the narrowing component, ≥ 6 (≥ 4 for isolated ileal disease, as scored by the site investigator)
aAEs leading to death: Prior to rescue, multiple organ dysfunction syndrome (180 mg SC), sudden cardiac death (180 mg SC), and gastric cancer (360 mg SC); on/after rescue, cardiac arrest (360 mg SC).
|
Conclusion
Among pts with moderate-to-severe CD who experienced IR to RZB maintenance therapy during the FORTIFY OLE, many demonstrated clinically meaningful improvements in symptomatic and endoscopic outcomes after receiving RZB rescue treatment, durable to two years and beyond. No new safety risks for RZB were identified with rescue treatment, supporting its long-term use in treating CD.
References
- Ferrante M, et al. UEG J. 2025;13(11):13-15.
- Ferrante M, et al. J Crohns Colitis. 2025;19(Suppl 1):i113-i115.
- Ferrante M, et al. J Crohns Colitis. 2024;18(Suppl 1):i168-i170.
- Papp KA, et al. J Am Acad Dermatol. 2024;91(3):AB60.
- Östör A, et al. Skin J Cutan Med. 2025;9(6):s692.
- Papp KA, et al. Am J Clin Dermatol. 2025;26(5):829-841.
Disclosure
Remo Panaccione Consulting fees from AbbVie, Abbott, Alimentiv, Amgen, Arena, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Ferring, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Lilly, Merck, Mylan, Oppilan Pharma, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Schering-Plough, Shire, Sublimity Therapeutics, Theravance, UCB, and Takeda; speaker fees from AbbVie, Arena, Celgene, Ferring, Gilead Sciences, Janssen, Lilly, Merck, Pfizer, Roche, Sandoz, Shire, and Takeda; and research/educational support from AbbVie, Ferring, Janssen, Pfizer, and Takeda. He has served on an advisory board for AbbVie, Amgen, Arena, Bristol Myers Squibb, Celgene, Celltrion, Ferring, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Lilly, Merck, Mylan, Oppilan Pharma, Pandion Pharma, Pfizer, Sandoz, Shire, Sublimity Therapeutics, Takeda, and Theravance.
Jean-Frederic Colombel Research grants from AbbVie, Janssen Pharmaceuticals, and Takeda; payment for lectures from AbbVie, Allergan, Amgen, Ferring Pharmaceuticals, Shire, and Takeda; consulting fees from AbbVie, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Celgene Corporation, Ferring Pharmaceuticals, Galmed Research, Genentech, GlaxoSmithKline, Imedex, Immunic, Iterative Scopes, Janssen Pharmaceuticals, Kaleido Biosciences, Lilly, Merck, Microbia, Novartis, PBM Capital, Pfizer, Protagonist Therapeutics, Sanofi, Takeda, TiGenix, and Vifor; and holds stock options in Intestinal Biotech Development.
Marla Dubinsky Consulting fees from AbbVie, Abivax, Astra Zeneca, , Boehringer Ingelheim, Bristol Myers Squibb, Celttrion, Eli Lilly, Genentech, , Janssen, Johnson and Johnson, Merck Pfizer, Prometheus Labs, Sanofi, Spyre, Takeda, Tentarix.
Tadakazu Hisamatsu Grant support from AbbVie, Daiichi-Sankyo, EA Pharma Co, Ltd. JIMRO, Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Pfizer Inc., Takeda Pharmaceutical Co., Ltd. Consulting fees from EA Pharma Co, Ltd., Janssen Research & Development, LLC., Gilead Sciences, Eli Lilly, Bristol Myers Squibb. Lecture fees from AbbVie, EA Pharma Co, Ltd, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd., Kissei Pharmaceutical Co, Ltd.
James O. Lindsay has received consultancy fees from AbbVie, Astra Zeneca, BMS, Celgene, Celltrion, Engytix, Ferring, Galapagos, Gilead, GSK, Janssen, Lilly, MSD, Orchard, Pfizer, Shattuck Labs and Takeda; has received speaker fees and travel support from AbbVie, Ferring, Galapagos, Gilead, High5MD, Janssen, Lilly, Materia Prima, MSD, Pfizer, Tillott’s, and Takeda; and has received investigator-led research grants from AbbVie, Gilead, Pfizer, and Takeda.
Geert D’Haens Consultant for AbbVie, AgomAb, AstraZeneca, AM Pharma, AMT, Bristol Myers Squibb, Boehringer Ingelheim, Celltrion, Eli Lilly, Exeliom Biosciences, Exo Biologics, Galapagos, Index Pharmaceuticals,, GSK, Pfizer, Immunic, J&J, Origo, Polpharma, Procise Diagnostics, Prometheus Laboratories, Prometheus Biosciences, Progenity, Protagonist and Ventyx; and has received speakers bureau fees from AbbVie, Arena Pharmaceuticals, Galapagos, Gilead, Pfizer, Bristol Myers Squibb, 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, MRM, MSD, Numab Therapeutics, Pfizer, Regeneron, Samsung Bioepis, Sandoz, Takeda, ThermoFisher and ZipBio; Speakers’ fees from: AbbVie, Amgen, Biogen, Boehringer Ingelheim, Falk, Ferring, Janssen-Cilag, Lamepro, MSD, Pfizer, Sandoz, Takeda, Truvion Healthcare and Viatris
Alexandra Song, Yi Yao, Ying Zhang, Javier Zambrano, Fernando Aponte, and W. Rachel Duan are full-time employees of AbbVie and may own AbbVie stock or options.
Acknowledgements: 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 Catherine Barone of AbbVie.
