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Clinical Trial
. 2024 Mar 1;18(3):416-423.
doi: 10.1093/ecco-jcc/jjad168.

Maintenance Risankizumab Sustains Induction Response in Patients with Crohn's Disease in a Randomized Phase 3 Trial

Marc Ferrante  1 , Peter M Irving  2 , Maria T Abreu  3 , Jeffrey Axler  4 , Xiang Gao  5 , Qian Cao  6 , Toshimitsu Fujii  7 , Astrid Rausch  8 , Joana Torres  9   10   11 , Ezequiel Neimark  12 , Alexandra Song  12 , Kori Wallace  12 , Kristina Kligys  12 , Sofie Berg  12 , Xiaomei Liao  12 , Qing Zhou  12 , Jasmina Kalabic  13 , Brian Feagan  14 , Remo Panaccione  15
Affiliations
Clinical Trial

Maintenance Risankizumab Sustains Induction Response in Patients with Crohn's Disease in a Randomized Phase 3 Trial

Marc Ferrante et al. J Crohns Colitis. .

Abstract

Background and aims: Durable clinical remission, endoscopic healing, and biomarker normalization are key treatment goals for Crohn's disease. The selective anti-interleukin-23 p19 inhibitor risankizumab has demonstrated efficacy and safety in moderately to severely active Crohn's disease. This post-hoc analysis of data from the pivotal risankizumab maintenance study assessed whether risankizumab maintenance therapy sustained the clinical and endoscopic outcomes achieved with risankizumab induction therapy.

Methods: We evaluated 462 patients who achieved a clinical response to risankizumab intravenous induction treatment and were re-randomized to receive subcutaneous risankizumab 360 mg, subcutaneous risankizumab 180 mg, or placebo [withdrawal] every 8 weeks for 52 weeks in the randomized, controlled FORTIFY maintenance study. Maintenance of clinical, endoscopic, and biomarker endpoints at week 52 among patients who achieved these endpoints after 12 weeks of induction treatment was evaluated.

Results: A significantly higher proportion of patients receiving maintenance treatment with risankizumab 360 or 180 mg compared with placebo [withdrawal] maintained Crohn's Disease Activity Index remission [68.6%, 70.8%, vs 56.3%; p < 0.05], stool frequency/abdominal pain remission [69.2%, 64.1%, vs 50.5%; p < 0.01], endoscopic response [70.2%, 68.2%, vs 38.4%; p < 0.001], endoscopic remission [74.4%, 45.5%, vs 23.9%; p < 0.05], and Simple Endoscopic Score for Crohn's Disease of 0-2 [65.5%, 36.7%, vs 21.9%]. Most patients [56.8-83.3%] who achieved normalized faecal calprotectin or C-reactive protein during induction sustained them with maintenance risankizumab.

Conclusions: Subcutaneous risankizumab maintenance therapy results in durable improvement in clinical and endoscopic outcomes over 1 year in patients with moderately to severely active Crohn's disease.

Clinical trial registration number: NCT03105102.

Keywords: Crohn’s disease; Risankizumab; durability.

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Conflict of interest statement

M.F. has received 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, MSD, Pfizer, Regeneron, Samsung Bioepis, Sandoz, Takeda, and Thermo Fisher; and speakers’ fees from AbbVie, Amgen, Biogen, Boehringer Ingelheim, Dr Falk, Ferring, Janssen-Cilag, Lamepro, MSD, Pfizer, Sandoz, Takeda, Truvion Healthcare, and Viatris. P.M.I. has received speaking fees from AbbVie, Bristol Myers Squibb, Celgene, Celltrion, Falk Pharma, Ferring, Galapagos, Gilead, MSD, Janssen, Lilly, Pfizer, Takeda, Tillotts, Sapphire Medical, Sandoz, Shire, and Warner Chilcott; research grants from Celltrion, Galapagos, MSD, Pfizer, and Takeda; and advisory fees from AbbVie, Arena, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Genentech, Gilead, Hospira, Janssen, Lilly, MSD, Pfizer, Pharmacosmos, Prometheus, Roche, Sandoz, Samsung Bioepis, Takeda, Topivert, VH2, Vifor, and Warner Chilcott. M.T.A. has served as a consultant for AbbVie, Allergan, Amgen, Boehringer Ingelheim, Celgene, Cornerstones Health, Focus Medical Communications, Gilead Sciences, Imedex, Janssen Biotech, Landos, Lilly, Nestec, Pfizer, Prometheus Laboratories, Roche Pharmaceuticals, Shire, Takeda, and Vindico Medical Education. J.A. has served as a consultant for AbbVie, Janssen Pharmaceutical, and Takeda. X.G. and QC. report no conflicts of interest. T.F. has received research grants from AbbVie, Alfresa, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, EA Pharma, Eisai, Gilead, Janssen, Kissei, Lilly, Mebix, Sanofi, and Takeda; and speaking honoraria from AbbVie, Ajinomoto Pharma, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, EA Pharma, Eisai, Janssen, Kissei, Kyorin, Kyowa Hakko Kirin, Kissei Pharma, Mitsubishi Tanabe, Mochida, Nichiiko, Nippon Kayaku, Pfizer, Taiho, Takeda, and Zeria Pharma. A.R. has received speaking fees from AbbVie, Ferring, Janssen, and Takeda. J.T. has received speaker’s fees from AbbVie, Galapagos, Janssen, and Pfizer; advisory fees from AbbVie, Janssen, and Pfizer; and research grants from AbbVie and Janssen. E.N., A.S., K.W., K.K., S.B., Q.Z., and J.K. are employees of AbbVie and may own AbbVie stock or options. X.L. is a former employee of AbbVie and may own AbbVie stock or options. B.F. has received consulting fees from AbbVie, Allergan, ActoGeniX, Albireo, Amgen, AstraZeneca, Atlantic Pharma, Avaxia Biologics, Axcan, Baxter Healthcare Corp, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Centocor, Elan/Biogen, enGene, Ferring, Genentech, GICare, Gilead, Given Imaging Inc, GlaxoSmithKline, Ironwood, Johnson & Johnson/Janssen, Kyowa Hakko Kirin, Lycera, Lexicon, Lilly, Merck, Mesoblast, Millennium, Nektar, Novartis Novo Nordisk, Prometheus, Pfizer, Protagonist, Receptos, Salix, Serono, Shire, Sigmoid, Synergy, Takeda, Teva, Tillotts, TiGenix, UCB, Warner-Chilcott, Wyeth, Zealand, and Zyngenia; speaker fees from AbbVie, Johnson & Johnson/Janssen, Takeda, and UCB; financial support for research from AbbVie, Amgen, AstraZeneca/MedImmune, Atlantic Pharmaceuticals, Boehringer Ingelheim, Celgene Corporation, Celltech, Genentech Inc/Hoffmann–La Roche, Gilead, GlaxoSmithKline, Janssen Research & Development, Pfizer, Receptos/Celgene, Sanofi, Santarus, Takeda Development Center Americas, Tillotts, and UCB; and has served as a member of the board of directors of Robarts Clinical Trials, Inc. R.P. has served as a consultant for Abbott, AbbVie, Alimentiv, Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Ferring, Galapagos, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Lilly, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Takeda, Theravance Biopharma, Trellus, Viatris, and UCB. He has received speaking fees from AbbVie, Amgen, Arena Pharmaceuticals, Bristol-Myers Squibb, Celgene, Ferring, Fresenius Kabi, Gilead Sciences, Janssen, Lilly, Merck, Organon, Pfizer, Roche, Sandoz, Shire, and Takeda Pharmaceuticals; and advisory fees from AbbVie, Alimentiv, Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Ferring, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Lilly, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pfizer, Progenity, Protagonist, Roche, Sandoz, Shire, Sublimity Therapeutics, and Takeda.

Figures

Figure 1.
Figure 1.
Maintenance of CDAI clinical remission and SF/AP clinical remission at week 52 among patients with the same outcome at the end of the induction period. Error bars represent the lower and upper bounds of the 95% confidence interval [95% CI]. Values above brackets are the adjusted treatment difference [95% CI]. AP, abdominal pain; CDAI, Crohn’s Disease Activity Index; PBO, placebo; RZB, risankizumab, SC, subcutaneous; SF, stool frequency.
Figure 2.
Figure 2.
Maintenance of endoscopic response, endoscopic remission, and SES-CD of 0–2 at week 52 among patients with the same outcome at the end of the induction period. Error bars represent the lower and upper bounds of the 95% confidence interval [95% CI]. Values above brackets are the adjusted treatment difference [95% CI]. PBO, placebo; RZB, risankizumab; SC, subcutaneous; SES-CD, Simple Endoscopic Score for Crohn’s Disease.
Figure 3.
Figure 3.
Maintenance of deep remission [CDAI clinical remission plus endoscopic remission] and SF/AP clinical remission plus endoscopic remission at week 52 among patients with the same outcome at the end of the induction period. Error bars represent the lower and upper bounds of the 95% confidence interval [95% CI]. Values above brackets are the adjusted treatment difference [95% CI]. AP, abdominal pain; CDAI, Crohn’s Disease Activity Index; PBO, placebo; RZB, risankizumab, SC, subcutaneous; SF, stool frequency.
Figure 4.
Figure 4.
Maintenance of FCP ≤ 250 mg/kg, maintenance of FCP ≤ 250 mg/kg and CDAI clinical remission, and maintenance of FCP ≤ 250 mg/kg and SF/AP clinical remission at week 52 among patients who had elevated FCP at baseline and achieved the same outcome at the end of the induction period. Error bars represent the lower and upper bounds of the 95% confidence interval [95% CI]. Values above brackets are the adjusted treatment difference [95% CI]. AP, abdominal pain; CDAI, Crohn’s Disease Activity Index; FCP, faecal calprotectin; PBO, placebo; RZB, risankizumab, SC, subcutaneous; SF, stool frequency.
Figure 5.
Figure 5.
Maintenance of hs-CRP concentration of ≤ 5 mg/L, maintenance of hs-CRP concentration of ≤ 5 mg/L and CDAI clinical remission, and maintenance of hs-CRP concentration of ≤ 5 mg/L and SF/AP clinical remission at week 52 among patients who had elevated hs-CRP concentrations at baseline and achieved the same outcome at the end of the induction period. Error bars represent the lower and upper bounds of the 95% confidence interval [95% CI]. Values above brackets are the adjusted treatment difference [95% CI]. AP, abdominal pain; CDAI, Crohn’s Disease Activity Index; hs-CRP, high-sensitivity C-reactive protein; PBO, placebo; RZB, risankizumab, SC, subcutaneous; SF, stool frequency.
Figure 6.
Figure 6.
Mean SES-CD over time. Error bars represent the lower and upper bounds of the 95% confidence interval. PBO, placebo; RZB, risankizumab, SC, subcutaneous; SES-CD, Simple Endoscopic Score for Crohn’s Disease.
See this image and copyright information in PMC

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