Risankizumab: Mechanism of action, clinical and translational science.
Journal
Clinical and translational science
ISSN: 1752-8062
Titre abrégé: Clin Transl Sci
Pays: United States
ID NLM: 101474067
Informations de publication
Date de publication:
Jan 2024
Jan 2024
Historique:
revised:
09
11
2023
received:
31
08
2023
accepted:
06
12
2023
medline:
24
1
2024
pubmed:
24
1
2024
entrez:
24
1
2024
Statut:
ppublish
Résumé
Risankizumab is a high-affinity neutralizing anti-interleukin (IL)-23 monoclonal antibody marketed in over 40 countries across the globe to treat several inflammatory diseases, such as plaque psoriasis (PsO), psoriatic arthritis (PsA), and Crohn's disease (CD). This paper reviews the regulatory approval, mechanism of action, pharmacokinetics (PKs)/pharmacodynamics, immunogenicity, and clinical efficacy and safety data for risankizumab, focusing on the three main approved indications. Risankizumab binds to the p19 subunit of IL-23 and inhibits IL-23 from interacting with the IL-23 receptor and subsequent signaling. Biomarker data obtained following treatment with risankizumab in multiple indications provided supportive evidence for downstream blockade of IL-23 signaling associated with disease pathology. The PKs of risankizumab is linear and time-independent, consistent with typical IgG1 monoclonal antibodies, across all evaluated indications. Risankizumab exhibited positive exposure-response relationships for efficacy with no apparent exposure-dependent worsening in safety. Immunogenicity to risankizumab had no major clinical consequences for either efficacy or safety. Efficacy and safety of risankizumab have been established in PsO, PsA, and CD in the pivotal clinical trials where superior benefit/risk profiles were demonstrated compared to placebo and/or active comparators. Moreover, safety evaluations in open-label extension studies following long-term treatment with risankizumab showed stable and favorable safety profiles consistent with shorter-term studies. These data formed the foundation for risankizumab's marketing approvals to treat multiple inflammatory diseases across the globe.
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13706Informations de copyright
© 2024 AbbVie Inc. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.
Références
Iwakura Y, Nakae S, Saijo S, Ishigame H. The roles of IL-17A in inflammatory immune responses and host defense against pathogens. Immunol Rev. 2008;226:57-79.
Lee E, Trepicchio WL, Oestreicher JL, et al. Increased expression of interleukin 23 p19 and p40 in lesional skin of patients with psoriasis vulgaris. J Exp Med. 2004;199:125-130.
Celis R, Planell N, Fernández-Sueiro JL, et al. Synovial cytokine expression in psoriatic arthritis and associations with lymphoid neogenesis and clinical features. Arthritis Res Ther. 2012;14:R93.
Liu Z, Yadav PK, Xu X, et al. The increased expression of IL-23 in inflammatory bowel disease promotes intraepithelial and lamina propria lymphocyte inflammatory responses and cytotoxicity. J Leukoc Biol. 2011;89:597-606.
McDonald BD, Dyer EC, Rubin DT. IL-23 monoclonal antibodies for IBD: so many, so different? J Crohns Colitis. 2022;16:ii42-ii53.
Zhou L, Wang Y, Wan Q, et al. A non-clinical comparative study of IL-23 antibodies in psoriasis. MAbs. 2021;13:1964420.
AbbVie Inc. Skyrizi® (risankizumab-rzaa). [US Package Insert] 2023.
Pang Y, Khatri A, Suleiman AA, Othman AA. Clinical pharmacokinetics and pharmacodynamics of Risankizumab in psoriasis patients. Clin Pharmacokinet. 2020;59:311-326.
Suleiman AA, Minocha M, Khatri A, Pang Y, Othman AA. Population pharmacokinetics of Risankizumab in healthy volunteers and subjects with moderate to severe plaque psoriasis: integrated analyses of phase I-III clinical trials. Clin Pharmacokinet. 2019;58:1309-1321.
Thakre N, D'Cunha R, Goebel A, Liu W, Pang Y, Suleiman AA. Population pharmacokinetics and exposure-response analyses for Risankizumab in patients with active psoriatic arthritis. Rheumatol Ther. 2022;9:1587-1603.
Suleiman AA, Goebel A, Bhatnagar S, D'Cunha R, Liu W, Pang Y. Population pharmacokinetic and exposure-response analyses for efficacy and safety of Risankizumab in patients with active Crohn's disease. Clin Pharmacol Ther. 2023;113:839-850.
Khatri A, Suleiman AA, Polepally AR, Othman AA. Exposure-response relationships for efficacy and safety of Risankizumab in phase II and III trials in psoriasis patients. Clin Pharmacol Ther. 2020;107:378-387.
Khatri A, Cheng L, Camez A, Ignatenko S, Pang Y, Othman AA. Lack of effect of 12-week treatment with Risankizumab on the pharmacokinetics of cytochrome P450 probe substrates in patients with moderate to severe chronic plaque psoriasis. Clin Pharmacokinet. 2019;58:805-814.
Visvanathan S, Baum P, Vinisko R, et al. Psoriatic skin molecular and histopathologic profiles after treatment with risankizumab versus ustekinumab. J Allergy Clin Immunol. 2019;143:2158-2169.
Ravishankar B, Lal P, Sornasse T, et al. POS1545 modulation of serum biomarkers in patients with PSA treated with RISANKIZUMAB in the phase 3 keepsake 2 study. Ann Rheum Dis. 2023;82:1141-1142.
Visvanathan S, Baum P, Salas A, et al. Selective IL-23 inhibition by Risankizumab modulates the molecular profile in the colon and Ileum of patients with active Crohn's disease: results from a randomised phase II biopsy sub-study. J Crohns Colitis. 2018;12:1170-1179.
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;399:2031-2046.
D'Haens G, Panaccione R, Baert F, et al. Risankizumab as induction therapy for Crohn's disease: results from the phase 3 ADVANCE and MOTIVATE induction trials. Lancet. 2022;399:2015-2030.
Feagan BG, Sandborn WJ, D'Haens G, et al. Induction therapy with the selective interleukin-23 inhibitor risankizumab in patients with moderate-to-severe Crohn's disease: a randomised, double-blind, placebo-controlled phase 2 study. Lancet. 2017;389:1699-1709.
Gordon K, Strober B, Lebwohl M, et al. Efficacy and safety of Risankizumab: results from two double-blind, randomised, placebo- and Ustekinumab-controlled, phase 3 trials in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2). Lancet. 2018;392:650-661.
Reich K, Gooderham M, Thaçi D, et al. Risankizumab compared with adalimumab in patients with moderate-to-severe plaque psoriasis (IMMvent): a randomised, double-blind, active-comparator-controlled phase 3 trial. Lancet. 2019;394:576-586.
Cestari TF, Souza CD, Azulay-Abulafia L, et al. 26197 efficacy and safety of risankizumab vs methotrexate in patients with moderate-to-severe plaque psoriasis: results from the 28-week randomized, double-blind period of an ongoing phase 3 study in Brazil. J Am Acad Dermatol. 2021;85:AB88.
Papp K, Blauvelt A, Puig L, et al. Long-term safety and efficacy of risankizumab for the treatment of moderate-to-severe plaque psoriasis: interim analysis of the limmitless open-label extension trial up to 5 years of follow-up. J Am Acad Dermatol. 2023;89(6):1149-1158.
Kristensen LE, Keiserman M, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 52-week results from the KEEPsAKE 1 study. Rheumatology (Oxford). 2023;62:2113-2121.
Ostor A, Van den Bosch F, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 52-week results from the KEEPsAKE 2 study. Rheumatology (Oxford). 2023;62:2122-2129.
Mease PJ, Kellner H, Morita A, et al. Long-term efficacy and safety of Risankizumab in patients with active psoriatic arthritis: results from a 76-week phase 2 randomized trial. Rheumatol Ther. 2022;9:1361-1375.
Ferrante M, Feagan BG, Panés J, et al. Long-term safety and efficacy of Risankizumab treatment in patients with Crohn's disease: results from the phase 2 open-label extension study. J Crohns Colitis. 2021;15:2001-2010.
Sanchez AP, da Costa A, Del Rey C, Silva B, Romiti R. The overview of the immunobiology of Interleukin-23 associated with immune-mediated inflammatory disorders: a narrative review. J Drugs Dermatol. 2023;22:375-385.
Chiricozzi A, Saraceno R, Chimenti MS, Guttman-Yassky E, Krueger JG. Role of IL-23 in the pathogenesis of psoriasis: a novel potential therapeutic target? Expert Opin Ther Targets. 2014;18:513-525.
Eken A, Singh AK, Oukka M. Interleukin 23 in Crohn's disease. Inflamm Bowel Dis. 2014;20:587-595.