Vnitr Lek 2025, 71(5):E19-E28

Upadacitinib: JAK inhibitor for the treatment of rheumatoid arthritis

Daniel Zuzčák, Petra Matalová
Farmakologický ústav LF UP a FN Olomouc

Upadacitinib (UPA), a JAK inhibitor, is classified as a tsDMARD, a targeted synthetic disease-modifying antirheumatic drug. It was first approved by the FDA in August 2019 and by the European Commission in December of the same year. Unlike monoclonal antibodies, UPA is a very small molecule with a molecular weight of 380 Da (daltons), which makes it preferable for oral administration. It is currently one of the leading drugs in the treatment of rheumatoid arthritis.

Keywords: upadacitinib, rheumatoid arthritis, JAK inhibitor.

Accepted: August 29, 2025; Published: September 18, 2025  Show citation

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Zuzčák D, Matalová P. Upadacitinib: JAK inhibitor for the treatment of rheumatoid arthritis. Vnitr Lek. 2025;71(5):E19-28.
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    References

    1. Klener P, Bultas J, Widimský J. Interní lékařství. 6. vyd. Praha: Galén; 2020.
    2. Agashe R, Lippman S, Kurzrock R. JAK: Not Just Another Kinase. Mol Cancer Ther. 2022;???-???. Go to original source... Go to PubMed...
    3. Jinesh S, Radhakrishnan R. Pharmaceutical aspects of JAK inhibitors: a comparative review. Inflammopharmacol. 2025;???-???. Go to original source...
    4. Schwartz D, Kanno Y, Villarino A, et al. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov. 2017;???-???. Go to original source...
    5. Ding Q, Hu W, Wang R, et al. Signaling pathways in rheumatoid arthritis: implications for targeted therapy. Signal Transduct Target Ther. 2023;8(1):68. Go to original source... Go to PubMed...
    6. Sanmartí R, Corominas H. Upadacitinib for patients with rheumatoid arthritis: a comprehensive review. J Clin Med. 2023;12(5):1734. Go to original source... Go to PubMed...
    7. Mohamed M, Klünder B, Ahmed A, et al. Clinical pharmacokinetics of upadacitinib: review of data relevant to the rheumatoid arthritis indication. Clin Pharmacokinet. 2020;59:531-544. Go to original source... Go to PubMed...
    8. Center for Drug Evaluation and Research. Application number 211675Orig1s000 summary review. [Internet]. FDA; 2019 [cited???]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211675Orig1s000SumR.pdf
    9. Klünder B, Mittapalli R, Mohamed M, 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):1045-1058. Go to original source... Go to PubMed...
    10. European Medicines Agency. Rinvoq: summary of product characteristics. [Internet]. EMA;??? [cited???]. Available from: https://www.ema.europa.eu/cs/documents/product-information/rinvoq-epar-product-information_cs.pdf
    11. Smolen J, Landewé R, Bergstra S, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023;82(1):3-18. Go to original source... Go to PubMed...
    12. Fraenkel L, Bathon J, England B, et al. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2021;73(7):924-939. Go to original source... Go to PubMed...
    13. U.S. Food and Drug Administration. Janus kinase (JAK) inhibitors: drug safety communication - FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death. [Internet]. FDA; 2021 [cited 2025-05-12]. Available from: https://www.fda.gov/safety/medical-product-safety-information/janus-kinase-jak-inhibitors-drug-safety-communication-fda-requires-warnings-about-increased-risk
    14. European Medicines Agency. EMA recommends measures to minimise risk of serious side effects with Janus kinase inhibitors for chronic inflammatory disorders. [Internet]. EMA; 2022 [cited???]. Available from: https://www.ema.europa.eu/en/news/ema-recommends-measures-minimise-risk-serious-side-effects-janus-kinase-inhibitors-chronic-inflammatory-disorders
    15. Vallez-Valero L, Gasó-Gago I, Marcos-Fendian Á, et al. Are all JAK inhibitors for the treatment of rheumatoid arthritis equivalent? An adjusted indirect comparison of the efficacy of tofacitinib, baricitinib, upadacitinib, and filgotinib. Clin Rheumatol. 2023;42:3225-3235. Go to original source... Go to PubMed...
    16. de Souza S, Williams R, Nikiphorou E. Clinician and patient views on Janus kinase inhibitors in the treatment of inflammatory arthritis: a mixed-methods study. BMC Rheumatol. 2024;8(1):1. Go to original source... Go to PubMed...
    17. Fleischmann R, Pangan A, Song I, et al. Upadacitinib versus placebo or adalimumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a Phase III double-blind randomized controlled trial. Arthritis Rheumatol. 2019;71(11):1788-1800. Go to original source... Go to PubMed...
    18. Fleischmann R, Mysler E, Bessette L, et al. Long-term safety and efficacy of upadacitinib or adalimumab in patients with rheumatoid arthritis: results through 3 years from the SELECT-COMPARE study. RMD Open. 2022;8(1):e002012. Go to original source... Go to PubMed...
    19. Fleischmann R, Meerwein S, Charles-Schoeman C, et al. Efficacy and safety of upadacitinib in patients with rheumatoid arthritis and inadequate response or intolerance to biological treatments: results through 5 years from the SELECT-BEYOND study. RMD Open. 2024;10(3):e003918. Go to original source... Go to PubMed...
    20. van Vollenhoven R, Strand V, Takeuchi T, et al. Upadacitinib monotherapy versus methotrexate monotherapy in patients with rheumatoid arthritis: efficacy and safety through 5 years in the SELECT-EARLY randomized controlled trial. Arthritis Res Ther. 2024;26:143. Go to original source... Go to PubMed...
    21. Smolen J, Pangan A, Emery P, et al. Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate (SELECT-MONOTHERAPY): a randomised placebo-controlled double-blind Phase 3 study. Lancet. 2019; 393(10188):2303-2311. Go to original source... Go to PubMed...
    22. Smolen J, Pangan A, Emery P, et al. Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate: results at 260 weeks from the SELECT-MONOTHERAPY study. Ann Rheum Dis. 2023;82(Suppl 1):723. Go to original source...
    23. Strand V, Tundia N, Wells A, et al. Upadacitinib monotherapy improves patient-reported outcomes in rheumatoid arthritis: results from SELECT-EARLY and SELECT-MONOTHERAPY. Rheumatology (Oxford). 2021;60(7):3209-3221. Go to original source... Go to PubMed...
    24. Rubbert-Roth A, Enejosa J, Pangan A, et al. Trial of upadacitinib or abatacept in rheumatoid arthritis. N Engl J Med. 2020;383(16):1511-1521. Go to original source... Go to PubMed...
    25. Rubbert-Roth A, Kato K, Haraoui B, et al. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis refractory to biologic DMARDs: results through week 216 from the SELECT-CHOICE study. Rheumatol Ther. 2024;11(5):1197-1215. Go to original source... Go to PubMed...
    26. Burmester G, Cohen S, Winthrop K, et al. Safety profile of upadacitinib over 15 000 patient-years across rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and atopic dermatitis. RMD Open. 2023;9(1):e002735. Go to original source... Go to PubMed...
    27. van Vollenhoven R, Takeuchi T, Pangan A, et al. Efficacy and safety of upadacitinib monotherapy in methotrexate-naïve patients with moderately-to-severely active rheumatoid arthritis (SELECT-EARLY): a multicenter multi-country randomized double-blind active-comparator-controlled trial. Arthritis Rheumatol. 2020;72(10):1607-1620. Go to original source... Go to PubMed...
    28. Avci A, Feist E, Burmester G. The role of upadacitinib in the treatment of moderate-to-severe active rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2021;13:1759720X211047662. Go to original source... Go to PubMed...
    29. Clarke B, Yates M, Adas M, et al. The safety of JAK-1 inhibitors. Rheumatology (Oxford). 2021;60(Suppl 2):ii24-ii30. Go to original source... Go to PubMed...
    30. Paolino G, Valenti M, Carugno A, et al. Serum lipids alterations in patients under systemic JAK inhibitor treatments in dermatology: clinical aspects and management. Medicina. 2025;61:54. Go to original source... Go to PubMed...
    31. Makris A, Barkas F, Sfikakis P, et al. The effect of upadacitinib on lipid profile and cardiovascular events: a meta-analysis of randomized controlled trials. J Clin Med. 2022;11(23):6894. Go to original source... Go to PubMed...
    32. Ouranos K, Avila D, Mylona E, et al. Cumulative incidence and risk of infection in patients with rheumatoid arthritis treated with Janus kinase inhibitors: a systematic review and meta-analysis. PLoS One. 2024;19(7):e0306548. Go to original source... Go to PubMed...
    33. Winthrop K, Nash P, Yamaoka K, et al. Incidence and risk factors for herpes zoster in patients with rheumatoid arthritis receiving upadacitinib: a pooled analysis of six Phase III clinical trials. Ann Rheum Dis. 2022;81(2):206-213. Go to original source... Go to PubMed...
    34. Alves C, Penedones A, Mendes D, et al. The risk of infections associated with JAK inhibitors in rheumatoid arthritis: a systematic review and network meta-analysis. J Clin Rheumatol. 2022;28(2):e407-e414. Go to original source... Go to PubMed...
    35. Simon T, Thompson A, Gandhi K, et al. Incidence of malignancy in adult patients with rheumatoid arthritis: a meta-analysis. Arthritis Res Ther. 2015;17:212. Go to original source... Go to PubMed...
    36. Song Y, Cho S, You S, et al. Association between malignancy risk and Janus kinase inhibitors versus tumour necrosis factor inhibitors in Korean patients with rheumatoid arthritis: a nationwide population-based study. RMD Open. 2022;8(2):e002614. Go to original source... Go to PubMed...
    37. Russell M, Stovin C, Alveyn E, et al. JAK inhibitors and the risk of malignancy: a meta-analysis across disease indications. Ann Rheum Dis. 2023;82(8):1059-1067. Go to original source... Go to PubMed...
    38. Ytterberg S, Bhatt D, Mikuls T, et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022;386:316-326. Go to original source... Go to PubMed...
    39. Bukhari M, Bergman M, Giles J, et al. Safety of jakinibs: lessons from ORAL Surveillance. Rheumatology (Oxford). 2022;61(11):4223-4225. Go to original source... Go to PubMed...
    40. Singh J. Risks and benefits of Janus kinase inhibitors in rheumatoid arthritis - past, present and future. N Engl J Med. 2022;386(4):387-389. Go to original source... Go to PubMed...
    41. ??? Biomolecules image g003. [Internet].???;??? [cited???]. Available from: https://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom & p=PMC3 & id=7408575_biomolecules-10-01002-g003.jpg
    42. Creative BioMart. Signal pathway: JAK-STAT. [Internet]. Creative BioMart;??? [cited???]. Available from: https://www.creativebiomart.net/resource/signal-pathway-jak-stat-signal-pathway-389.htm

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