Begünstigen Biologika die Entwicklung von Neoplasien?

Zusammenfassung

Metaanalysen und Daten aus den Biologika-Registern sprechen nicht dafür, dass durch den Einsatz von Biologika ein signifikant erhöhtes Neoplasierisiko besteht. Die bisherigen Analysen zu der Thematik beschränken sich aber fast ausschließlich auf den Einsatz von TNF-Inhibitoren (in geringem Maße wurde auch der IL-1-Antagonist Anakinra untersucht). Bedenken muss man die schon durch die Erkrankung selbst bedingte erhöhte Inzidenz bestimmter Neoplasien (insbesondere Lymphome) und die Assoziation von Malignomen mit der Krankheitsaktivität und der Komorbidität bei der RA und wahrscheinlich auch bei anderen entzündlich rheumatischen Erkrankungen. Für Hauttumoren (NMSC, eventuell auch für Melanome) kann ein leicht erhöhtes Risiko durch eine Anti-TNF-Therapie nicht ausgeschlossen werden. Bei Patienten mit Malignomen in der Vorgeschichte wird mit zunehmend geringerem Abstand von der Tumorerkrankung ein Biologikum eingesetzt. Dabei wird oft Rituximab bevorzugt. Die Rezidivrate von Neoplasien ist unter TNF-Inhibitoren nicht signifikant erhöht, unter Rituximab wahrscheinlich eher niedriger als unter konventionellen DMARDs.

Summary

Meta-analyses and data from biologic-registries do not indicate that there is a significantly increased risk for developing neoplasia with use of biologics. However, studies so far rely almost exclusively on the use of TNF-inhibitors. One has to be aware that the diseases itself harbor an increased risk of certain malignancies (especially lymphoma) and in addition that risk is associated with the activity and comorbidity of RA and probably other inflammatory rheumatic diseases. A slightly increased risk for skin cancers (NMSC, possibly also for melanoma) under anti-TNF therapy cannot be ruled out. In patients with prior malignancies in their history a biologic agent is used with increasingly less latency from the tumour disease, in this situation rituximab is often preferred. The recurrence rate of neoplasia is not significantly increased under therapy with TNF-inhibitors and probable lower under therapy with rituximab compared to conventional DMARDs.

Schlüsselwörter

Biologika - Neoplasie - Lymphom - Malignom

Keywords

Biologics - neoplasia - lymphoma - malignancies

• Literatur

• 1 Carswell EA, Old LJ, Kassel RL. et al. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci USA 1975; 72 (09) 3666-3670 PubMed PMID:
• 2 Smitten AL, Simon TA, Hochberg MC, Suissa S. A meta-analysis of the incidence of malignancy in adult patients with rheumatoid arthritis. Arthritis Res Ther. 2008 10. (2): R45 doi: Epub 2008 Apr 23. PubMed PMID:
• 3 Bernatsky S, Ramsey-Goldman R, Labrecque J. et al. Cancer risk in systemic lupus: an updated international multi-centre cohort study. J Autoimmun. 2013 42. 130-135 doi: Epub 2013 Feb 12. PubMed PMID:
• 4 Wolfe F, Michaud K. The effect of methotrexate and anti-tumor necrosis factor therapy on the risk of lymphoma in rheumatoid arthritis in 19,562 patients during 89,710 person-years of observation. Arthritis Rheum 2007; 56 (05) 1433-14439 PubMed PMID:
• 5 Gross RL, Schwartzman-Morris JS, Krathen M. et al. A comparison of the malignancy incidence among patients with psoriatic arthritis and patients with rheumatoid arthritis in a large US cohort. Arthritis Rheumatol. 2014 66. (6): 1472-1481 doi: PubMed PMID:
• 6 Choi HK, Hernán MA, Seeger JD. et al. Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study. Lancet 2002; 359 (9313): 1173-1177 PubMed PMID:
• 7 Alarcón GS, McGwin G, Bertoli AM. et al. LUMINA Study Group. Effect of hydroxychloroquine on the survival of patients with systemic lupus erythematosus: data from LUMINA, a multiethnic US cohort (LUMINA L). Ann Rheum Dis 2007; 66 (09) 1168-1172 Epub 2007 Mar 27. PubMed PMID:
• 8 Baecklund E, Iliadou A, Askling J. et al. Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis. Arthritis Rheum 2006; 54 (03) 692-701 PubMed PMID:
• 9 Tiippana-Kinnunen T, Kautiainen H, Paimela L, Leirisalo-Repo M. Co-morbidities in Finnish patients with rheumatoid arthritis: 15-year follow-up. Scand J Rheumatol. 2013 42. (6): 451-456 doi: Epub 2013 Jul 4. PubMed PMID:
• 10 Bongartz T. et al. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: Systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA 2006; 295: 2275-2285.
• 11 Leombruno JP, Einarson TR, Keystone EC. The safety of anti-tumour necrosis factor treatments in rheumatoid arthritis: meta and exposure-adjusted pooled analyses of serious adverse events. Ann Rheum Dis. 2009 68. (7): 1136-1145 doi: Epub 2008 Aug 27. Review. PubMed PMID:
• 12 Askling J, Fahrbach K, Nordstrom B. et al. Cancer risk with tumor necrosis factor alpha (TNF) inhibitors: meta-analysis of randomized controlled trials of adalimumab, etanercept, and infliximab using patient level data. Pharmacoepidemiol Drug Saf.. 2011 20. (2): 119-130 doi: Epub 2010 Dec 7. PubMed PMID:
• 13 Tumor necrosis factor therapy and the risk of serious infection and malignancy in patients with early rheumatoid arthritis: a meta-analysis of randomized controlled trials. Arthritis Rheum. 2011 63. (6): 1479-1485 doi: PubMed PMID:
• 14 Askling J, van Vollenhoven RF, Granath F. et al. Cancer risk in patients with rheumatoid arthritis treated with anti-tumor necrosis factor alpha therapies: does the risk change with the time since start of treatment?. Arthritis Rheum. 2009 60. (11): 3180-3189 doi: PubMed PMID:
• 15 Dreyer L, Mellemkjær L, Andersen AR. et al. Incidences of overall and site specific cancers in TNFá inhibitor treated patients with rheumatoid arthritis and other arthritides - a follow-up study from the DANBIO Registry. Ann Rheum Dis. 2013 72. (1): 79-82 doi: Epub 2012 Sep 3. PubMed PMID:
• 16 Strangfeld A, Hierse F, Rau R. et al. Risk of incident or recurrent malignancies among patients with rheumatoid arthritis exposed to biologic therapy in the German biologics register RABBIT. Arthritis Res Ther 2010; 12: R5.
• 17 Wolfe F, Michaud K. Biologic treatment of rheumatoid arthritis and the risk of malignancy: analyses from a large US observational study. Arthritis Rheum 2007; 56 (09) 2886-2895 PubMed PMID:
• 18 Mercer LK, Lunt M, Low AL. et al. BSRBR Control Centre Consortium. Risk of solid cancer in patients exposed to anti-tumour necrosis factor therapy: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis. Ann Rheum Dis.. 2014 Mar 31. doi: [Epub ahead of print] PubMed PMID:
• 19 Mariette X, Tubach F, Bagheri H. et al. Lymphoma in patients treated with anti-TNF: results of the 3-year prospective French RATIO registry. Ann Rheum Dis. 2010 69. (2): 400-408 doi: Epub 2009 Oct 14. PubMed PMID:
• 20 Dixon WG, Watson KD, Lunt M. et al. British Society For Rheumatology Biologics Register Control Centre Consortium; British Society for Rheumatology Biologics Register. Influence of anti-tumor necrosis factor therapy on cancer incidence in patients with rheumatoid arthritis who have had a prior malignancy: results from the British Society for Rheumatology Biologics Register. Arthritis Care Res (Hoboken). 2010 62. (6): 755-763 doi:
• 21 Strangfeld A, Pattloch D, Herzer P. et al. Risk Of Cancer Recurrence Or New Tumors In RA Patients With Prior Malignancies Treated With Various Biologic Agents. Arthritis Rheum 2013; 65 (11) 342.