Upadacitinib: First Approval
Upadacitinib (Rinvoq™), an orally-administered Janus kinase 1 (JAK-1) inhibitor, is being developed by AbbVie for the treatment of rheumatoid arthritis. In August 2019, based on positive results from multinational phase III trials conducted in patients with rheumatoid arthritis, upadacitinib received marketing approval in the USA for the treatment of moderately to severely active rheumatoid arthritis and an inadequate response or intolerance to methotrexate. This article summarizes the milestones in the development of upadacitinib leading to this first approval for the treatment of rheumatoid arthritis.
Compliance with Ethical Standards
The preparation of this review was not supported by any external funding.
Conflict of interest
During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the authors on the basis of scientific completeness and accuracy. Sean Duggan and Susan Keam are salaried employees of Adis International Ltd/Springer Nature, are responsible for the article content and declare no relevant conflicts of interest.
- 1.Genovese MC, Fleischmann R, Combe B, et al. Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease-modifying anti-rheumatic drugs (SELECT-BEYOND): a double-blind, randomised controlled phase 3 trial. Lancet. 2018;391(10139):2513–24.CrossRefGoogle Scholar
- 2.AbbVie. AbbVie receives FDA approval of RINVOQTM (upadacitinib), an oral JAK inhibitor for the treatment of moderate to severe rheumatoid arthritis [media release]. 16 Aug 2019. http://www.abbvie.com.
- 3.AbbVie. RINVOQ™ (upadacitinib) extended-release tablets, for oral use: US prescribing information. 2019. https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed 2019.
- 5.Sornasse T, Sokolove J, McInnes I. Treatment with upadacitinib results in the normalization of key pathobiologic pathways in patients with rheumatoid arthritis: Biomarker results from the phase 3 selectnext and select-beyond studies [abstract no. THU0181]. Ann Rheum Dis. 2019;78(Suppl. 2):365–6.Google Scholar
- 6.Nurmohamed M, Zhang Y, Lin J, et al. Changes in C-reactive protein and lipid levels in patients with rheumatoid arthritis treated with ABT-494 a selective JAK-1 inhibitor [abstract no. THU0203]. Ann Rheum Dis. 2017;76(Suppl. 2):280.Google Scholar
- 7.Charles-Schoeman C, Sornasse T, Sokolove J. Treatment with upadacitinib is associated with improvements in reverse cholesterol transport in patients with rheumatoid arthritis: correlation with changes in inflammation and HDL levels [abstract no. THU0166]. Ann Rheum Dis. 2019;78(Suppl. 2):356–7.Google Scholar
- 13.Klunder B, Mittapalli RK, Mohamed MF, et al. Population pharmacokinetics of upadacitinib using the immediate-release and extended-release formulations in healthy subjects and subjects with rheumatoid arthritis: analyses of phase I-III clinical trials. Clin Pharmacokinet. 2019;58(8):1045–58.CrossRefGoogle Scholar
- 19.Mohamed MF, Feng T, Enejosa JV, et al. Effects of upadacitinib coadministration on the pharmacokinetics of sensitive cytochrome P450 probe substrates: a study with the modified Cooperstown 5 + 1 cocktail. J Clin Pharmacol. 2019. https://doi.org/10.1002/jcph.1496.CrossRefPubMedPubMedCentralGoogle Scholar
- 20.Burmester GR, Kremer JM, Van den Bosch F, et al. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (SELECT-NEXT): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018;391(10139):2503–12.CrossRefGoogle Scholar
- 21.Burmester GR, Van Den Bosch F, Bessette L, et al. Long-term safety and efficacy of upadacitinib in patients with rheumatoid arthritis and an inadequate response to CSDMARDS: results at 60 weeks from the select-next study [abstract no. FRI0132]. Ann Rheum Dis. 2019;78(Suppl. 2):735–6.Google Scholar
- 22.Genovese MC, Combe B, Hall S, et al. Upadacitinib in patients with rheumatoid arthritis and inadequate response or intolerance to biological DMARDS: results at 60 weeks from the select-beyond study [abstract no. THU0172]. Ann Rheum Dis. 2019;78(Suppl. 2):360–1.Google Scholar
- 24.Fleischmann R, Pangan AL, Song IH, et al. Upadacitinib versus placebo or adalimumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase 3, double-blind, randomized controlled trial. Arthritis Rheumatol. 2019. https://doi.org/10.1002/art.41032.CrossRefPubMedPubMedCentralGoogle Scholar
- 25.Fleischmann RM, Genovese MC, Enejosa JV, et al. Safety and effectiveness of upadacitinib or adalimumab plus methotrexate in patients with rheumatoid arthritis over 48 weeks with switch to alternate therapy in patients with insufficient response. Ann Rheum Dis. 2019. https://doi.org/10.1136/annrheumdis-2019-215764.CrossRefPubMedGoogle Scholar
- 26.Van Vollenhoven R, Takeuchi T, Pangan AL, et al. A phase 3, randomized, controlled trial comparing upadacitinib monotherapy to MTX monotherapy in MTX-naive patients with active rheumatoid arthritis [abstract no. 891]. Arthritis Rheumatol. 2018;70(Suppl 9):990–2.Google Scholar
- 27.Van Vollenhoven R, Takeuchi T, Pangan A, et al. Monotherapy with upadacitinib in MTX-naive patients with rheumatoid arthritis: results at 48 weeks from the select-early study [abstract no. THU0197]. Ann Rheum Dis. 2019;78(Suppl. 2):376–7.Google Scholar
- 28.Tanaka Y, Takeuchi T, Yamaoka K, et al. A phase 2b/3 randomised, placebo-controlled, double-blind study of upadacitinib, a selective jak1 inhibitor, in Japanese patients with active rheumatoid arthritis and inadequate response to conventional synthetic DMARDs [abstract no. SAT0257]. Ann Rheum Dis. 2018;77(Suppl 2):991–2.Google Scholar
- 31.Genovese MC, Kremer J, Zhong S, et al. Long-term safety and efficacy of upadacitinib (ABT-494), an oral JAK-1 inhibitor in patients with rheumatoid arthritis in an open label extension study [abstract no. SAT0236]. Ann Rheum Dis. 2018;77(Suppl 2):979.Google Scholar
- 33.Panes J, Sandborn WJ, Loftus EV, et al. Efficacy and safety of upadacitinib maintenance treatment for moderate to severe Crohn’s disease: results from the CELEST study [abstract no. 906]. Gastroenterology. 2018;154(6 Suppl 1):S-178–9.Google Scholar
- 35.Reich K, Guttman-Yassky E, Beck LA, et al. Early response to upadacitinib in moderate-to-severe atopic dermatitis: results from a phase 2B randomized, placebo-controlled trial [abstract no. 0135]. Allergy Eur J Allergy Clin Immunol. 2018;73(Suppl. 105):76.Google Scholar
- 36.Sandborn WJ, Ghosh S, Panes J, et al. Efficacy and safety of upadacitinib as an induction therapy for patients with moderately-to-severely active ulcerative colitis: data from the phase 2b study U-ACHIEVE [abstract no. OP195]. United Eur Gastroenterol. 2018;6(8 Suppl):A74–5.Google Scholar
- 37.Cohen SB, Van Vollenhoven R, Winthrop K, et al. Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the SELECT phase 3 clinical program [abstract no. THU0167]. Ann Rheum Dis. 2019;78(Suppl 2):357.Google Scholar