Neue Sicherheitsdaten zu JAK-Inhibitoren bei rheumatoider Arthritis

Zusammenfassung

Während die Wirksamkeit von Januskinase-Inhibitoren (JAKi) für die Behandlung der rheumatoiden Arthritis (RA) unumstritten ist, gibt es weitreichende Diskussionen bezüglich ihrer Sicherheit. Risiken hinsichtlich des Auftretens kardiovaskulärer und thromboembolischer Ereignisse, schwerer Infektionen und Krebserkrankungen wurden in umfangreichen Analysen mit Daten aus klinischen Studien, aber insbesondere in prospektiv angelegten RA-Registern untersucht. In dieser Arbeit geben wir einen Überblick über die neuesten Daten zur Sicherheit von JAKi für Patienten mit RA und fassen die derzeitigen Empfehlungen zusammen.

Abstract

While the efficacy of Janus kinase inhibitors (JAKi) for the treatment of rheumatoid arthritis (RA) is undisputed, there is widespread debate regarding their safety. Risks related to the occurrence of cardiovascular and thromboembolic events, serious infections, and malignancies have been investigated in extensive analyses, using data from clinical trials, and, in particular, in prospective RA registers. This paper provides an overview of the latest safety data for JAKi in patients with RA and summarises the current recommendations.

Schlüsselwörter

tsDMARDs - kardiovaskuläre Ereignisse - thromboembolische Ereignisse - Infektionen - Malignome

Keywords

tsDMARDs - cardiovascular events - thromboembolic events - serious infections - malignancies

Publication History

Received: 17 June 2025

Accepted: 22 August 2025

Article published online:
21 October 2025

• Literatur

• 1 Szekanecz Z, Buch MH, Charles-Schoeman C. et al. Efficacy and safety of JAK inhibitors in rheumatoid arthritis: update for the practising clinician. Nat Rev Rheumatol 2024; 20: 101-115
• 2 Ytterberg SR, Bhatt DL, Mikuls TR. et al. Cardiovascular and Cancer Risk with Tofacitinib in Rheumatoid Arthritis. N Engl J Med 2022; 386: 316-326
• 3 Albrecht K, Thiele K, Alexander T. et al Jahresbericht 2025 aus der Kerndokumentation der Regionalen Kooperativen Rheumazentren. Z Rheumatol 2025; Online ahead of print.
• 4 European Medicines Agency (EMA). Xeljanz (tofacitinib): Initial clinical trial results of increased risk of major adverse cardiovascular events and malignancies (excluding NMSC) with use of tofacitinib relative to TNF–alpha inhibitors. https://www.ema.europa.eu/en/medicines/dhpc/xeljanz-tofacitinib-initial-clinical-trial-results-increased-risk-major-adverse-cardiovascular abgerufen am 19.05.2025.
• 5 U.S. Food & Drug Administration (FDA). Administration FUSFD. Initial safety trial results find increased risk of serious heart-related problems and cancer with arthritis and ulcerative colitis medicine Xeljanz, Xeljanz XR (tofacitinib). https://www.fda.gov/drugs/drug-safety-and-availability/initial-safety-trial-results-find-increased-risk-serious-heart-related-problems-and-cancer-arthritis abgerufen am 19.05.2025.
• 6 Salinas CA, Louder A, Polinski J. et al. Evaluation of VTE, MACE, and Serious Infections Among Patients with RA Treated with Baricitinib Compared to TNFi: A Multi-Database Study of Patients in Routine Care Using Disease Registries and Claims Databases. Rheumatol Ther 2023; 10: 201-223
• 7 European Medicines Agency (EMA). EMA confirms measures to minimise risk of serious side effects with Janus kinase inhibitors for chronic inflammatory disorders (EMA/27681/2023). https://www.ema.europa.eu/en/medicines/human/referrals/janus-kinase-inhibitors-jaki abgerufen am 19.05.2025.
• 8 Smolen JS, Landewe RBM, Bergstra SA. 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: 3-18
• 9 Tian Z, Kearsley-Fleet L, Galloway J. et al. Potential impact of European Medicines Agency measures to minimize risk of serious side effects on JAKi prescribing and utilization in the UK. Rheumatology (Oxford) 2025; 64: 1453-1458
• 10 Deutsche Gesellschaft für Rheumatologie und Immunologie e.v. (DGRh). Aktualisierte Empfehlungen der Deutschen Gesellschaft für Rheumatologie und Klinische Immunologie: Januskinase-Inhibitoren (JAKi) – wie ist mit den Verordnungseinschränkungen umzugehen?. Stand 17.10.2024: https://dgrh.de/Start/Publikationen/Empfehlungen/Medikation/Januskinase-Inhibitoren-(JAKi)0.html abgerufen am 10.05.2025.
• 11 Nash P, Kerschbaumer A, Konzett V. et al. Expert consensus statement on the treatment of immune-mediated inflammatory diseases with Janus kinase inhibitors: 2024 update. Ann Rheum Dis 2025; 84: 664-679
• 12 Konzett V, Smolen JS, Nash P. et al. Efficacy of Janus kinase inhibitors in immune-mediated inflammatory diseases a systematic literature review informing the 2024 update of an international consensus statement. Ann Rheum Dis 2025; 84: 680-696
• 13 Konzett V, Smolen JS, Nash P. et al. Safety of Janus kinase inhibitors in immune-mediated inflammatory diseases – a systematic literature review informing the 2024 update of an international expert consensus statement. Ann Rheum Dis 2025; 84: 697-715
• 14 Bower H, Frisell T, di Giuseppe D. et al. Comparative cardiovascular safety with janus kinase inhibitors and biological disease-modifying antirheumatic drugs as used in clinical practice: an observational cohort study from Sweden in patients with rheumatoid arthritis. RMD Open. 2023 9.
• 15 Meissner Y, Schäfer M, Albrecht K. et al. Risk of major adverse cardiovascular events in patients with rheumatoid arthritis treated with conventional synthetic, biologic and targeted synthetic disease-modifying antirheumatic drugs: observational data from the German RABBIT register. RMD Open. 2023 9.
• 16 Aymon R, Mongin D, Guemara R. et al. Incidence of major adverse cardiovascular events in patients with rheumatoid arthritis treated with Janus kinase inhibitors compared to biologic disease-modifying antirheumatic drugs: data from an international collaboration of registries (the "JAK-pot" study). Arthritis Rheumatol. 2025
• 17 Huss V, Bower H, Hellgren K. et al. Cancer risks with JAKi and biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis or psoriatic arthritis: a national real-world cohort study. Ann Rheum Dis 2023; 82: 911-919
• 18 Molina-Collada J, Alonso F, Otero L. et al. Cancer risk with biologic and targeted synthetic DMARDs in patients with rheumatic diseases and previous malignancies: Results from the BIOBADASER register. Semin Arthritis Rheum 2024; 64: 152341
• 19 Westermann R, Cordtz RL, Duch K. et al. Cancer risk in patients with rheumatoid arthritis treated with janus kinase inhibitors: a nationwide Danish register-based cohort study. Rheumatology (Oxford) 2024; 63: 93-102
• 20 Russell MD, Stovin C, Alveyn E. et al. JAK inhibitors and the risk of malignancy: a meta-analysis across disease indications. Ann Rheum Dis 2023; 82: 1059-1067
• 21 Schäfer M, Purschke A, Zietemann V. Comparative risk of incident malignancies in rheumatoid arthritis patients treated with Janus kinase inhibitors or bDMARDs: observational data from the German RABBIT register. Ann Rheum Dis 2025; S0003-4967: 01024-01026 Online ahead of print.
• 22 Aymon RM D, Gilbert B. et al. Cancer incidence among rheumatoid arthritis patients treated with JAK-inhibitors compared to bDMARDs: data from an international collaboration of registers (the “JAK-POT” study). Ann Rheum Dis 2025; 84: 193
• 23 Atsumi T, Asakura E, Doi M. et al. Number needed to treat and cost per responder of Janus kinase inhibitors approved for the treatment of moderate-to-severe rheumatoid arthritis in Japan. Mod Rheumatol 2023; 33: 54-63
• 24 Molander V, Bower H, Frisell T. et al. Venous thromboembolism with JAK inhibitors and other immune-modulatory drugs: a Swedish comparative safety study among patients with rheumatoid arthritis. Ann Rheum Dis 2023; 82: 189-197
• 25 Molander V, Bower H, Frisell T. et al. Risk of venous thromboembolism in rheumatoid arthritis, and its association with disease activity: a nationwide cohort study from Sweden. Ann Rheum Dis 2021; 80: 169-175
• 26 Balanescu AR, Citera G, Pascual-Ramos V. et al. Infections in patients with rheumatoid arthritis receiving tofacitinib versus tumour necrosis factor inhibitors: results from the open-label, randomised controlled ORAL Surveillance trial. Ann Rheum Dis 2022; 81: 1491-1503
• 27 Ouranos K, Avila DV, Mylona EK. 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: e0306548
• 28 Frisell T, Bower H, Morin M. et al. Safety of biological and targeted synthetic disease-modifying antirheumatic drugs for rheumatoid arthritis as used in clinical practice: results from the ARTIS programme. Ann Rheum Dis 2023; 82: 601-610
• 29 Winthrop K, Isaacs J, Calabrese L. et al. Opportunistic infections associated with Janus kinase inhibitor treatment for rheumatoid arthritis: A structured literature review. Semin Arthritis Rheum 2023; 58: 152120
• 30 Redeker I, Albrecht K, Kekow J. et al. Risk of herpes zoster (shingles) in patients with rheumatoid arthritis under biologic, targeted synthetic and conventional synthetic DMARD treatment: data from the German RABBIT register. Ann Rheum Dis 2022; 81: 41-47
• 31 Feuchtenberger M, Kovacs MS, Nigg A. et al. Detection of substantial numbers of latent tuberculosis and positive hepatitis B serology results in rheumatology patients preparing to receive intensified immunosuppressive therapy in a low-prevalence country: why screening still matters. Clin Rheumatol 2025; 44: 1851-1859
• 32 Rudi T, Zietemann V, Meissner Y. et al. Impact of DMARD treatment and systemic inflammation on all-cause mortality in patients with rheumatoid arthritis and interstitial lung disease: a cohort study from the German RABBIT register. RMD Open. 2024 10.
• 33 Narvaez J, Diaz Del Campo Fontecha P, Brito Garcia N. et al. SER-SEPAR recommendations for the management of rheumatoid arthritis-related interstitial lung disease. Part 2: Treatment. Reumatol Clin (Engl Ed) 2022; 18: 501-512
• 34 Fiehn C, Leipe J, Weseloh C. et al. Bewertung von Wechselwirkungen und Dosierungsempfehlungen von synthetischen DMARDs – Evidenz- und konsensbasierte Empfehlungen auf Basis einer systematischen Literatursuche. Z Rheumatol 2023; 82: 151-162
• 35 Ruegg L, Pluma A, Hamroun S. et al. EULAR recommendations for use of antirheumatic drugs in reproduction, pregnancy, and lactation: 2024 update. Ann Rheum Dis. 2025 Apr 25 online first
• 36 Reinisch W, Hellstrom W, Dolhain R. et al. Effects of filgotinib on semen parameters and sex hormones in male patients with inflammatory diseases: results from the phase 2, randomised, double-blind, placebo-controlled MANTA and MANTA-RAy studies. Ann Rheum Dis 2023; 82: 1049-1058
• 37 Deutsche Gesellschaft für Rheumatologie und Immunologie e.v. (DGRh). Therapieüberwachungsbögen. Therapie mit Baricitinib, Filgotinib, Tofacitinib, Upadacitinib unter: https://dgrh.de/Start/Versorgung/Therapieinformationen/Therapieinformationsb%C3%B6gen.html abgerufen am 19.05.2025.
• 38 Robert Koch Institut (RKI) Wissenschaftliche Begründung zur Empfehlung einer Impfung mit dem Herpes zoster-subunit-Totimpfstoff. Epidemiologisches Bulletin 50/2018