Subscribe to RSS
DOI: 10.1055/a-0732-4736
Sicherheit von Biologika bei rheumatoider Arthritis: Ergebnisse aus dem deutschen RABBIT-Register
Safety of Biologics in Rheumatoid Arthritis: Results from the German RABBIT RegisterPublication History
Publication Date:
02 October 2018 (online)
![](https://www.thieme-connect.de/media/rheuma/201805/lookinside/thumbnails/2018-08-0550_10-1055-a-0732-4736-1.jpg)
Zusammenfassung
Hintergrund Das Biologika-Register RABBIT erfasst Krankheits- und Therapieverläufe von Patienten mit rheumatoider Arthritis (RA). Neben der Wirksamkeit von Biologika (bDMARDs: Originals und Biosimilars) und JAK-Inhibitor (JAKi) Therapien sind Daten zur Sicherheit, insbesondere in der Langzeittherapie, ein wesentlicher Bestandteil der Analysen aus RABBIT.
Methoden In das RABBIT-Register können Patienten mit einer gesicherten RA eingeschlossen werden, die nach mindestens einem konventionell synthetischen (cs)DMARD-Versagen eine neue cs-, bDMARD oder JAKi Therapie beginnen. Über 300 rheumatologische Einrichtungen schließen deutschlandweit Patienten in das Register ein. Einmal rekrutiert, werden die Patienten bis zu 10 Jahre lang beobachtet. Zu Beginn und im Verlauf werden Therapie, klinischer Status, Krankheitsverlauf und aufgetretene unerwünschte Ereignisse dokumentiert. In dieser Übersichtsarbeit werden relevante Ergebnisse aus dem RABBIT Register zur Sicherheit der bDMARDs bei RA zusammengefasst.
Ergebnisse Bis zum Frühjahr 2018 wurden über 17 000 RA Patienten in das RABBIT Register eingeschlossen. Die Daten aus 17 Beobachtungsjahren zeigen, dass das Risiko für schwerwiegende Infektionen unter bDMARDs erhöht ist. Das individuelle Risiko kann mit dem RABBIT Risiko Score abgeschätzt werden. Die Mortalität ist im Vergleich zu Patienten unter csDMARDs verringert. Auch das Risiko für das Auftreten einer Sepsis oder Versterben nach schwerwiegender Infektion ist unter bDMARDs erniedrigt. Hohe Krankheitsaktivität und eine unzureichende Behandlung kardiovaskulärer Komorbiditäten erhöhen das Risiko für das Auftreten kardiovaskulärer Ereignisse. Gemeinsame Auswertungen der Daten europäischer Biologika-Register zeigen kein erhöhtes Risiko für das Auftreten von Melanomen oder eine Verschiebung der Subtypen der Lymphome.
Fazit Insgesamt zeigen bDMARDs bei RA ein gutes Sicherheitsprofil. Kenntnis über die individuellen Risikofaktoren des Patienten, eine engmaschige Kontrolle der Krankheitsaktivität der RA und der Begleiterkrankungen sind wesentliche Faktoren, die das Auftreten von unerwünschten Ereignissen reduzieren können.
Abstract
Background The German RABBIT biologics register records the course of disease and therapy in patients with rheumatoid arthritis (RA). In addition to the effectiveness of biologics (bDMARDs), data on the safety of therapies, especially in long-term monitoring, are an essential part of the analyses from RABBIT.
Methods Patients with confirmed RA, who start a new conventional synthetic (cs) or bDMARD therapy after at least one csDMARD failure, can be included in the RABBIT register. More than 300 rheumatological units include patients in the register. Once enrolled, patients are monitored for up to 10 years. At baseline and follow-up visits, exact details on treatment, clinical status, course of disease and adverse events are documented. This review summarises relevant results from the RABBIT register on the safety of bDMARDs in RA.
Results By spring 2018, more than 17,000 RA patients were included in the RABBIT register. Data from 17 years of observation show that the risk of serious infections is increased in patients on bDMARDs. The individual risk can be approximated with the RABBIT Risk Score. Mortality is lower compared to patients on csDMARDs. Also the risk of sepsis and mortality after serious infection is reduced on bDMARDs. High disease activity and inadequate treatment of cardiovascular comorbidities increase the risk of cardiovascular events. Collaborative analyses of data from the European biologics registers reveal no increased risk of melanomas or a different distribution of lymphoma subtypes.
Conclusion All in all, bDMARDs have a good safety profile in patients with RA. Knowledge of a patient’s individual risk factors and continuous monitoring of the disease activity of RA and concomitant diseases are essential factors that can reduce the occurrence of adverse events.
-
Literatur
- 1 Strangfeld A, Zink A. Safety of biologic therapy – results from the German biologics register RABBIT. Deutsche medizinische Wochenschrift 2014; 139: 1817-1820
- 2 Richter A, Meissner Y, Strangfeld A. et al. Primary and secondary patient data in contrast: the use of observational studies like RABBIT. Clinical and experimental rheumatology 2016; 34 5 Suppl 101 S79-S86
- 3 Askling J, Dixon W. The safety of anti-tumour necrosis factor therapy in rheumatoid arthritis. Current opinion in rheumatology 2008; 20: 138-144
- 4 Strangfeld A, Eveslage M, Schneider M. et al. Treatment benefit or survival of the fittest: what drives the time-dependent decrease in serious infection rates under TNF inhibition and what does this imply for the individual patient?. Annals of the rheumatic diseases 2011; 70: 1914-1920
- 5 Zink A, Manger B, Kaufmann J. et al. Evaluation of the RABBIT Risk Score for serious infections. Annals of the rheumatic diseases 2014; 73: 1673-1676
- 6 Keane J, Gershon S, Wise RP. et al. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. The New England journal of medicine 2001; 345: 1098-1104
- 7 Carmona L, Gómez-Reino JJ, Rodríguez-Valverde V. et al. Effectiveness of recommendations to prevent reactivation of latent tuberculosis infection in patients treated with tumor necrosis factor antagonists. Arthritis Rheum 2005; 52: 1766-1772
- 8 Rutherford AI, Patarata E, Subesinghe S. et al. Opportunistic infections in rheumatoid arthritis patients exposed to biologic therapy: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis. Rheumatology 2018; 57: 997-1001
- 9 Beutler B, Milsark IW, Cerami AC. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science 1985; 229: 869-871
- 10 Qiu P, Cui X, Sun J. et al. Antitumor necrosis factor therapy is associated with improved survival in clinical sepsis trials: a meta-analysis. Crit Care Med 2013; 41: 2419-2429
- 11 Richter A, Listing J, Schneider M. et al. Impact of treatment with biologic DMARDs on the risk of sepsis or mortality after serious infection in patients with rheumatoid arthritis. Annals of the rheumatic diseases 2016; 75: 1667-1673
- 12 Gonzalez A, Maradit Kremers H. et al. The widening mortality gap between rheumatoid arthritis patients and the general population. Arthritis and rheumatism 2007; 56: 3583-3587
- 13 Listing J, Kekow J, Manger B. et al. Mortality in rheumatoid arthritis: the impact of disease activity, treatment with glucocorticoids, TNFalpha inhibitors and rituximab. Annals of the rheumatic diseases 2015; 74: 415-421
- 14 Avina-Zubieta JA, Choi HK, Sadatsafavi M. et al. Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis and rheumatism 2008; 59: 1690-1697
- 15 Avina-Zubieta JA, Thomas J, Sadatsafavi M. et al. Risk of incident cardiovascular events in patients with rheumatoid arthritis: a meta-analysis of observational studies. Annals of the rheumatic diseases 2012; 71: 1524-1529
- 16 Fordjour PA, Wang Y, Shi Y. et al. Possible mechanisms of C-reactive protein mediated acute myocardial infarction. European journal of pharmacology 2015; 760: 72-80
- 17 Meissner Y, Zink A, Kekow J. et al. Impact of disease activity and treatment of comorbidities on the risk of myocardial infarction in rheumatoid arthritis. Arthritis research & therapy 2016; 18: 183
- 18 Emsley HC, Hopkins SJ. Acute ischaemic stroke and infection: recent and emerging concepts. Lancet Neurol. 2008; 7: 341-353
- 19 Nadav L, Gur AY, Korczyn AD. et al. Stroke in hospitalized patients: are there special risk factors?. Cerebrovasc Dis 2002; 13: 127-131
- 20 Meissner Y, Richter A, Manger B. et al. Serious adverse events and the risk of stroke in patients with rheumatoid arthritis: results from the German RABBIT cohort. Annals of the rheumatic diseases 2017; 76: 1583-1590
- 21 Hart AR, Kennedy HJ, Stebbings WS. et al. How frequently do large bowel diverticula perforate? An incidence and cross-sectional study. Eur J Gastroenterol Hepatol 2000; 12: 661-665
- 22 Strangfeld A, Richter A, Siegmund B. et al. Risk for lower intestinal perforations in patients with rheumatoid arthritis treated with tocilizumab in comparison to treatment with other biologic or conventional synthetic DMARDs. Annals of the rheumatic diseases 2017; 76: 504-510
- 23 Smitten AL, Simon TA, Hochberg MC. et al. A meta-analysis of the incidence of malignancy in adult patients with rheumatoid arthritis. Arthritis research & therapy 2008; 10: R45
- 24 Mercer LK, Regierer AC, Mariette X. et al. Spectrum of lymphomas across different drug treatment groups in rheumatoid arthritis: a European registries collaborative project. Annals of the rheumatic diseases 2017; 76: 2025-2030
- 25 Mercer LK, Askling J, Raaschou P. et al. Risk of invasive melanoma in patients with rheumatoid arthritis treated with biologics: results from a collaborative project of 11 European biologic registers. Annals of the rheumatic diseases 2017; 76: 386-391
- 26 Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J. et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. European journal of cancer (Oxford, England : 1990) 2013; 49: 1374-1403
- 27 Raaschou P, Simard JF, Holmqvist M. et al. Rheumatoid arthritis, anti-tumour necrosis factor therapy, and risk of malignant melanoma: nationwide population based prospective cohort study from Sweden. BMJ 2013; 346: f1939