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DOI: 10.1055/a-2246-6536
Neue Immunsuppressiva und das Risiko opportunistischer Infektionen
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ZUSAMMENFASSUNG
Die neuen therapeutischen Immunmodulatoren haben aufgrund ihres Wirkmechanismus unterschiedliche Infektionsrisiken. IL-1-Blockade erhöht vor allem das Risiko für bakterielle Infektionen. Die IL-5-hemmenden Substanzen bergen möglicherweise ein erhöhtes Risiko für Parasitosen. IL-6-Blockade führt zu einem erhöhten Risiko für schwere bakterielle und opportunistische Infektionen (OI), vergleichbar mit den TNF-α-Inhibitoren. Die IL-12/23-Blockade mit Ustekinumab zeigt wie auch der B-Lymphozyten-Stimulator (BLyS)-Inhibitor Belimumab im Vergleich mit anderen Therapeutika kein erhöhtes Infektionsrisiko. Unter einer IL-17-Hemmung ist vor allem mit gehäuften mukokutanen Kandidosen zu rechnen, insbesondere unter Bimekizumab. Der T-Zell-Aktivierungshemmer Abatacept erhöht das Risiko für Herpes Zoster (HZ), während andere Infektionen im Vergleich zu anderen Disease-Modifying Anti-Rheumatic Drugs (DMARD) sogar geringer sind. Auch Anifrolumab, ein Typ-1-Interferon-Inhibitor, erhöht das Risiko für HZ, aber auch für Atemwegsinfektionen. Beim Einsatz von Januskinase-Inhibitoren (JAKi) ist insbesondere mit HZ zu rechnen, wogegen andere OI seltener und in ihrer Häufigkeit mit den meisten älteren Biologika vergleichbar sind.
Schlüsselwörter
Opportunistische Infektionen - Disease-Modifying Anti-Rheumatic Drugs (DMARD - Interleukin-Antagonisten - Januskinase-Inhibitoren (JAKi) - Herpes ZosterPublication History
Article published online:
05 June 2024
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Literatur
- 1 Bălănescu AR, Citera G, Pascual-Ramos V. et al Incidence of Infections in Patients Aged ≥ 50 Years with RA and ≥ 1 Additional Cardiovascular Risk Factor: Results from a Phase 3b/4 Randomized Safety Study of Tofacitinib vs TNF Inhibitors. Abstract ACR Convergence 2021. Im Internet. https://acrabstracts.org/meetings/acr-convergence-2021/ Stand: 26.04.2024
- 2 Hsu C-Y, Ko C-H, Wang J-L. et al Comparing the burdens of opportunistic infections among patients with systemic rheumatic diseases: a nationally representative cohort study. Arthritis Res Ther 2019; 21: 211
- 3 Dave M, Purohit T, Razonable R. et al Opportunistic infections due to inflammatory bowel disease therapy. Inflamm Bowel Dis 2014; 20: 196-212
- 4 Winthrop KL, Mariette X, Silva JT. et al ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Soluble immune effector molecules II: agents targeting interleukins, immunoglobulins and complement factors). Clin Microbiol Infect 2018; 24 (Suppl. 02) S21-S40
- 5 Suárez I, Fünger SM, Kröger S. et al The Diagnosis and Treatment of Tuberculosis. Dtsch Arztebl Int 2019; 116: 729-735
- 6 Ridker PM, Everett BM, Thuren T. et al Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N Engl J Med 2017; 377: 1119-1131
- 7 Wagner N, Assmus F, Arendt G. et al Impfen bei Immundefizienz : Anwendungshinweise zu den von der Ständigen Impfkommission empfohlenen Impfungen. (IV) Impfen bei Autoimmunkrankheiten, bei anderen chronisch-entzündlichen Erkrankungen und unter immunmodulatorischer Therapie. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2019; 62: 494-515
- 8 Varricchi G, Senna G, Loffredo S. et al Reslizumab and Eosinophilic Asthma: One Step Closer to Precision Medicine?. Front Immunol 2017; 08: 242
- 9 Klion AD, Ackerman SJ, Bochner BS. Contributions of Eosinophils to Human Health and Disease. Annu Rev Pathol 2020; 15: 179-209
- 10 Jackson DJ, Akuthota P, Roufosse F. Eosinophils and eosinophilic immune dysfunction in health and disease. Eur Respir Rev 2022: 31
- 11 Pera V, Brusselle GG, Riemann S. et al Parasitic infections related to anti-type 2 immunity monoclonal antibodies: a disproportionality analysis in the food and drug administration’s adverse event reporting system (FAERS). Front Pharmacol 2023; 14: 1276340
- 12 Dropulic LK, Lederman HM. Overview of Infections in the Immunocompromised Host. Microbiol Spectr 2016: 4
- 13 Yamamoto K, Goto H, Hirao K. et al Longterm Safety of Tocilizumab: Results from 3 Years of Followup Postmarketing Surveillance of 5573 Patients with Rheumatoid Arthritis in Japan. J Rheumatol 2015; 42: 1368-1375
- 14 Schiff MH, Kremer JM, Jahreis A. et al Integrated safety in tocilizumab clinical trials. Arthritis Res Ther 2011; 13: R141
- 15 Burmester GR, Strand V, Kivitz AJ. et al Long-term safety and efficacy of sarilumab with or without background csDMARDs in rheumatoid arthritis. Rheumatology (Oxford) 2023; 62: 3268-3279
- 16 Cornberg M, Sandmann L, Protzer U. et al S3-Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) zur Prophylaxe, Diagnostik und Therapie der Hepatitis-B-Virusinfektion – (AWMF-Register-Nr. 021–11. Z Gastroenterol 2021; 59: 691-776
- 17 López-Ferrer A, Laiz A, Puig L. The safety of ustekinumab for the treatment of psoriatic arthritis. Expert Opin Drug Saf 2017; 16: 733-742
- 18 Danese S, Panaccione R, Feagan BG. et al Efficacy and safety of 48 weeks of guselkumab for patients with Crohn’s disease: maintenance results from the phase 2, randomised, double-blind GALAXI-1 trial. Lancet Gastroenterol Hepatol 2024; 09: 133-146
- 19 Strober B, Coates LC, Lebwohl MG. et al Long-Term Safety of Guselkumab in Patients with Psoriatic Disease: An Integrated Analysis of Eleven Phase II/III Clinical Studies in Psoriasis and Psoriatic Arthritis. Drug Saf 2024; 47: 39-57
- 20 Huang Y-H, Yen J-S, Li S-H. et al Safety Profile of Guselkumab in Treatment of Patients with Psoriasis and Coexisting Hepatitis B or C: A Multicenter Prospective Cohort Study. J Am Acad Dermatol 2024
- 21 Isailovic N, Daigo K, Mantovani A. et al Interleukin-17 and innate immunity in infections and chronic inflammation. J Autoimmun 2015; 60: 1-11
- 22 Berry SPD-G, Dossou C, Kashif A. et al The role of IL-17 and anti-IL-17 agents in the immunopathogenesis and management of autoimmune and inflammatory diseases. Int Immunopharmacol 2022; 102: 108402
- 23 Armstrong AW, Blauvelt A, Mrowietz U. et al A Practical Guide to the Management of Oral Candidiasis in Patients with Plaque Psoriasis Receiving Treatments That Target Interleukin-17. Dermatol Ther (Heidelb) 2022; 12: 787-800
- 24 Chiu H-Y, Hung Y-T, Huang Y-H. Comparative short-term risks of infection and serious infection in patients receiving biologic and small-molecule therapies for psoriasis and psoriatic arthritis: a systemic review and network meta-analysis of randomized controlled trials. Ther Adv Chronic Dis 2023; 14: 20406223231206225. doi:10.1177/20406223231206225.
- 25 Sthoeger Z, Lorber M, Tal Y. et al Anti-BLyS Treatment of 36 Israeli Systemic Lupus Erythematosus Patients. Isr Med Assoc J 2017; 19: 44-48
- 26 Chan J, Walters GD, Puri P. et al Safety and efficacy of biological agents in the treatment of Systemic Lupus Erythematosus (SLE). BMC Rheumatol 2023; 07: 37
- 27 Steiger S, Ehreiser L, Anders J. et al Biological drugs for systemic lupus erythematosus or active lupus nephritis and rates of infectious complications. Evidence from large clinical trials. Front Immunol 2022; 13: 999704
- 28 Kim J, Hasegawa T, Tada K. et al A Systemic Lupus Erythematosus Patient with Cutaneous Mycobacterium haemophilum Infection under Belimumab Treatment: A Case Report. Ann Dermatol 2023; 35: S63-S66
- 29 Simon TA, Dong L, Winthrop KL. Risk of opportunistic infections in patients with rheumatoid arthritis initiating abatacept: cumulative clinical trial data. Arthritis Res Ther 2021; 23: 17
- 30 Schiff M. Abatacept treatment for rheumatoid arthritis. Rheumatology (Oxford) 2011; 50: 437-449
- 31 Morand EF, Furie R, Tanaka Y. et al Trial of Anifrolumab in Active Systemic Lupus Erythematosus. N Engl J Med 2020; 382: 211-221
- 32 Kremer JM, Bingham CO, Cappelli LC. et al Postapproval Comparative Safety Study of Tofacitinib and Biological Disease-Modifying Antirheumatic Drugs: 5-Year Results from a United States-Based Rheumatoid Arthritis Registry. ACR Open Rheumatol 2021; 03: 173-184
- 33 Harrington R, Al Nokhatha SA, Conway R. JAK Inhibitors in Rheumatoid Arthritis: An Evidence-Based Review on the Emerging Clinical Data. J Inflamm Res 2020; 13: 519-531
- 34 Winthrop K, Isaacs J, Calabrese L. et al Opportunistische Infektionen im Zusammenhang mit der Behandlung von rheumatoider Arthritis mit Januskinase-Inhibitoren: eine strukturierte Literaturübersicht. Kompass Autoimmun 2023; 05: 104-113
- 35 Adas MA, Alveyn E, Cook E. et al The infection risks of JAK inhibition. Expert Rev Clin Immunol 18: 253-261
- 36 RKI – Archiv 2018 – Epidemiologisches Bulletin 50/2018. Im Internet. https://www.rki.de/DE/Content/Infekt/EpidBull/Archiv/2018/Ausgaben/50_18.html Stand: 07.01.2023
- 37 Cohen SB, Tanaka Y, Mariette X. et al Long-term safety of tofacitinib up to 9.5 years: a comprehensive integrated analysis of the rheumatoid arthritis clinical development programme. RMD Open 2020; 06: e001395
- 38 Smolen JS, Genovese MC, Takeuchi T. et al Safety Profile of Baricitinib in Patients with Active Rheumatoid Arthritis with over 2 Years Median Time in Treatment. J Rheumatol 2019; 46: 7-18
- 39 Kameda H, Takeuchi T, Yamaoka K. et al Efficacy and safety of upadacitinib over 84 weeks in Japanese patients with rheumatoid arthritis (SELECT-SUNRISE). Arthritis Res Ther 2021; 23: 9
- 40 Bechman K, Subesinghe S, Norton S. et al A systematic review and meta-analysis of infection risk with small molecule JAK inhibitors in rheumatoid arthritis. Rheumatology (Oxford) 2019; 58: 1755-1766
- 41 Winthrop KL, Park S-H, Gul A. et al Tuberculosis and other opportunistic infections in tofacitinib-treated patients with rheumatoid arthritis. Ann Rheum Dis 2016; 75: 1133-1138
- 42 Nash P, Kerschbaumer A, Dörner T. et al Points to consider for the treatment of immune-mediated inflammatory diseases with Janus kinase inhibitors: a consensus statement. Ann Rheum Dis 2021; 80: 71-87
- 43 Winthrop KL, Cohen SB. Oral surveillance and JAK inhibitor safety: the theory of relativity. Nat Rev Rheumatol 2022; 18: 301-304
- 44 Xeljanz – referral | European Medicines Agency. Im Internet. https://www.ema.europa.eu/en/medicines/human/referrals/xeljanz Stand: 11.01.2024
- 45 Fragoulis GE, Nikiphorou E, Dey M. et al 2022 EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis 2023; 82: 742-753