Introduction
Risankizumab (RZB) is a selective interleukin-23 p19 inhibitor approved for the treatment of moderate-to-severe Crohn’s disease (CD). Previously, RZB has demonstrated sustained efficacy and a consistent safety profile for up to 4 years (yrs) of maintenance treatment in the FORTIFY.1,2 This analysis evaluated the long-term efficacy and safety of RZB through 5 yrs of maintenance treatment in patients (pts) with moderate-to-severe CD.
Aims & Methods
Pts who completed the FORTIFY (NCT03105102) 52-wk double-blind randomised maintenance study and enrolled in the open-label extension (OLE) received 180 mg subcutaneous (SC) RZB every 8 weeks (wks) (Q8w), starting at wk 56, except for pts who had previously received rescue therapy (one dose of 1200 mg IV followed by 360 mg SC) due to inadequate response (IR; described in Table footnote); these pts received 360 mg SC Q8w in the OLE. CD Activity Index (CDAI) clinical response and clinical remission (per CDAI and per liquid or very soft stool frequency/abdominal pain score [SF/APS]) were assessed every 24 wks, while endoscopic response, endoscopic remission, ulcer-free endoscopy, and deep remission (clinical+endoscopic remission) were assessed at wks 56, 152, and 248 (endpoint definitions are in the Table footnotes). Data were analysed using as observed (AO) and modified nonresponder imputation (mNRI) methods (details in Table footnote). Treatment-emergent adverse events (TEAEs) reported on/after the first dose in the OLE were summarised for all pts not receiving rescue (cutoff date:25 November 2025).
Results
A total of 1112 pts who received ≥ 1 dose of RZB and who did not initiate rescue at entry to the OLE (180 mg, n = 852; 360 mg, n = 260) were included in this analysis. At induction baseline, 15.4% of pts had ileal-only disease and 71% of pts failed ≥1 biologics (95.1% failed ≥ 1 anti-tumour necrosis factor agents, 28.6% failed vedolizumab, and 19.0% failed ustekinumab), representing a refractory population. Per AO data, rates of clinical response, clinical remission per CDAI, and clinical remission per SF/APS remained stable through wk 248, while mNRI data showed slight reductions (Table). AO data showed increased rates for endoscopic endpoints from wk 56 to wk 248 (endoscopic response: 55.1% to 80.3%; endoscopic remission: 39.0% to 68.2%; ulcer-free endoscopy: 33.0% to 57.4%; deep remission: 29.3% to 59.3%). Notably, rates also remained stable or improved per mNRI analysis; in particular, the rates of deep remission increased from 28.2% to 39.9%. The exposure-adjusted event rates of serious TEAEs and TEAEs leading to discontinuation of RZB were low and consistent with RZB’s known AE profile (Table).2–4 The most common serious TEAE was worsening CD (1.2 events [E]/100 patient-years [PYs]). There were 3 deaths, none of which was considered to have a reasonable possibility of being related to RZB treatment (Table footnote).
Parameter, % (95% CI), n/N
| Week (From Entry to Maintenance Study) |
| 56 | 104 | 152 | 200 | 248 |
CDAI Clinical
Response
AO
mNRI
CDAI Clinical
Remission
AO
mNRI
SF/APS
Clinical Remission
AO
mNRI
Endoscopic
Response
AO
mNRI
Endoscopic
Remission
AO
mNRI
Ulcer-Free
Endoscopy
AO
mNRI
Deep
Remission
AO
mNRI
|
86.0 (83.9, 88.0),
955/1111
85.9 (83.8, 87.9),
955/1112
68.6 (65.9, 71.3),
763/1112
68.6 (65.9, 71.3),
763/1112
64.5 (61.7, 67.3),
717/1112
64.5 (61.7, 67.3),
717/1112
55.1 (52.1, 58.0),
588/1068
54.0 (51.1, 57.0),
601/1112
39.0 (36.1, 42.0),
417/1068
37.6 (34.8, 40.5),
419/1112
33.0 (30.2, 35.8),
351/1064
31.9 (29.1, 34.6),
353/1108
29.3 (26.6, 32.0),
313/1068
28.2 (25.6, 30.9),
314/1112
|
87.5 (85.2, 89.8),
697/797
78.7 (76.1, 81.2),
875/1112
76.5 (73.6, 79.5),
610/797
67.3 (64.2, 70.3),
748/1112
69.6 (66.5, 72.7),
587/843
60.4 (57.4, 63.4),
672/1112
|
87.5 (85.1, 90.0),
604/690
72.6 (69.8, 75.3),
807/1112
79.4 (76.4, 82.4),
548/690
63.4 (60.4, 66.3),
705/1112
72.3 (69.1, 75.6),
523/723
56.4 (53.4, 59.5),
627/1112
73.9 (70.8, 77.0),
572/774
58.5 (55.5, 61.5),
651/1112
58.8 (55.3, 62.3),
455/774
44.6 (41.5, 47.7),
496/1112
51.2 (47.6, 54.7),
395/772
38.1 (35.1, 41.2),
423/1108
50.9 (47.1, 54.8),
330/648
37.0 (34.0, 40.1),
412/1112
|
90.0 (87.6, 92.4),
540/600
69.7 (66.9, 72.6),
775/1112
82.8 (79.8, 85.9),
497/600
62.0 (58.9, 65.0),
689/1112
75.7 (72.4, 79.1),
484/639
55.0 (51.9, 58.2),
612/1112
|
92.7 (90.5, 94.9),
494/533
67.5 (64.6, 70.5),
751/1112
83.7 (80.5, 86.8),
446/533
59.6 (56.6, 62.7),
663/1112
76.3 (72.8, 79.8),
431/565
52.4 (49.2 55.6),
583/1112
80.3 (77.1, 83.5),
477/594
56.1 (52.9, 59.3),
624/1112
68.2 (64.4, 71.9),
405/594
45.3 (41.9, 48.6),
503/1112
57.4 (53.4, 61.4),
340/592
36.5 (33.3, 39.6),
404/1108
59.3 (55.0, 63.6),
296/499
39.9 (36.4, 43.3),
443/1112
|
TEAEs
|
|
|
|
| Pooled
(N=1112)
(PYs=3411.8)
Exposure-adjusted event rate (E/100PYs
|
All AEs
AEs related to study drug according to the investigator
Severe AE
Serious AE
AEs leading to discontinuation of RZB
AEs leading to deatha
|
|
|
|
| 5372 (157.5)
648 (19.0)
280 (8.2)
406 (11.9)
52 (1.5)
3 (<0.1)
|
TEAE, treatment-emergent 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; NRI, nonresponder imputation; RZB, risankizumab; SC, subcutaneous; SES-CD, Simple Endoscopic Score for Crohn’s Disease; SF, stool frequency.
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: decrease in SES-CD > 50% from BL of the induction study (or for pts with isolated ileal disease and a BL SES-CD = 4, ≥ a 2-point reduction from BL of the induction study); endoscopic remission: SES-CD ≤ 4 and at least a 2-point reduction versus BL of the induction study and no subscore > 1 in any individual variable; ulcer-free endoscopy: SES-CD ulcerated surface subscore of 0 in subjects with SES-CD ulcerated surface subscore ≥ 1 at BL of the induction study; deep remission: CDAI clinical remission and endoscopic remission.
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).
If a patient had IR as defined above, they could receive RZB rescue therapy, which is one dose of 1200 mg IV followed by 360 mg SC through the end of the trial.
For mNRI, pts were categorised as nonresponders for visits after (1) premature discontinuation of RZB due to primary reason of AE (limited to Crohn's disease) or lack of efficacy, and (2) initiation of rescue therapy.
aAEs leading to death: 180 mg SC, multiple organ dysfunction syndrome and sudden cardiac death; 360 mg SC, gastric cancer.
|
Conclusion
In the FORTIFY OLE, sustained and durable clinical and endoscopic benefits were observed with up to 5 yrs of long-term RZB maintenance therapy in pts with moderate-to-severe CD. No new safety risks for RZB were identified, supporting its long-term use in treating CD.
References
- Ferrante M, Panaccione R, Baert F, et al. Risankizumab as maintenance therapy for moderately to severely active Crohn’s disease: results from the multicentre, randomised, double-blind, placebo-controlled, withdrawal phase 3 FORTIFY maintenance trial. Lancet. 2022;399(10340):2031-2046. doi:10.1016/S0140-6736(22)00466-4
- Ferrante M. Efficacy and safety of risankizumab after 4 years of treatment in patients with moderate to severe Crohn’s disease: results from the FORTIFY open-label long-term extension. United Eur Gastroenterol J. 2025;13(11):13-15.
- Papp KA, Lebwohl MG, Puig L, et al. Long-term safety and efficacy of risankizumab to treat moderate-to-severe plaque psoriasis: final LIMMitless phase 3, open-label extension trial results. Am J Clin Dermatol. 2025;26(5):829-841. doi:10.1007/s40257-025-00964-6
- Östör A, Van Den Bosch F, Papp K, et al. Long-term efficacy and safety of risankizumab for active psoriatic arthritis: 244-week results from the KEEPsAKE 2 trial. Skin J Cutan Med. 2025;9(6):s692. doi:10.25251/w6str133
Disclosure
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, Pfizer, Regeneron, Samsung Bioepis, Sandoz, Takeda and ThermoFisher; Speakers’ fees from: AbbVie, Amgen, Biogen, Boehringer Ingelheim, Falk, Ferring, Janssen-Cilag, Lamepro, MSD, Pfizer, Sandoz, Takeda, Truvion Healthcare and Viatris
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 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
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, PhD, of AbbVie.
