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Komorbiditäten – ihre Rolle im Treat-to-Target-Konzept für die rheumatoide Arthritis

Comorbidities—Their role in the treat to target concept for rheumatoid arthritis

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Zusammenfassung

Treat-to-Target-Strategie und Komorbiditäten stehen in engem Zusammenhang zueinander. Die konsequente Umsetzung dieser Strategie mit folgender guter Einstellung der rheumatoiden Arthritis (RA) ist in der Lage, Risiko und Ausprägung von Komorbiditäten wie kardiovaskuläre Erkrankungen, Depression oder Infektionen zu verringern. Vorhandene Komorbiditäten können andererseits die Umsetzung des Treat-to-Target-Konzeptes erschweren oder sogar verhindern, indem sie die rheumatische Grundkrankheit verschlechtern oder den Behandler zu einer zu vorsichtigen DMARD(„disease modifying antirheumatic drugs“)-Therapie veranlassen. Aus der breiten Liste relevanter Komorbiditäten bei RA werden mit den kardiovaskulären (KV) Erkrankungen sowie Infektionen in der vorliegenden Übersicht 2 im Hinblick auf Treat-to-Target besonders relevante Begleiterkrankungen ausführlicher diskutiert. KV-Erkrankungen stellen die häufigste Todesursache bei RA dar und werden durch die RA-assoziierten Entzündungsmechanismen getriggert. Bestmögliche Kontrolle der RA-Aktivität, konsequenter Einsatz von Therapien wie den Biologika, Methotrexat und Hydroxychloroquin, die das KV-Risiko senken, sowie Erfassung und Behandlung traditioneller KV-Risikofaktoren sind die besten Möglichkeiten, den negativen Einfluss dieser Komorbidität auf die Umsetzung des Treat-to-Target-Konzeptes zu minimieren. Infektionen stellen eines der wichtigsten Risiken der DMARD-Therapie dar und können den optimalen Einsatz dieser Medikamente stören und damit die Treat-to-Target-Strategie behindern. Vor diesem Hintergrund kommt optimaler Infektionsprophylaxe und der Erkennung von Hochrisikopatienten besondere Bedeutung zu, außerdem der Minimierung des Einsatzes von Glukokortikoiden, die dosisabhängig besonders risikosteigernd wirken. Zusammengefasst stellen Komorbiditäten einen wichtigen potenziellen Störfaktor für die Umsetzung von Treat-to-Target dar.

Abstract

Treat to target (T2T) strategies and comorbidities are closely related. Strong evidence exists for reducing the risk and extent of comorbidities, such as cardiovascular (CV) diseases, depression and infections by implementing T2T concepts and inducing good disease control of rheumatoid arthritis (RA) in this way. On the other hand existing comorbidities may hinder implementation of T2T concepts by aggravating RA or influencing rheumatologists to overcautiously use DMARD treatment. Among a long list of potentially relevant comorbidities with RA, in this review two particularly relevant accompanying diseases with respect to T2T, CV diseases and infections, are selected for discussion in detail. The CV comorbidities are the main cause of death for RA patients and are triggered by RA-associated inflammatory mechanisms. Their negative influence on implementation of T2T strategies can be stopped or at least reduced by optimal control of RA activity with the help of selecting drugs with cardioprotective properties (such as biologicals, methotrexate and hydroxychloroquine) as well as assessing and treating traditional CV risk factors. Infections are among most important adverse events of DMARD treatment and can disturb the optimal use of these drugs and so hinder the success of the T2T strategy. Optimal infection prophylaxis and identification of high risk patients are particularly important and minimization of glucocorticoid use is critical to reduce the risk of infections. In summary, comorbidities are important potential risk factors for the success of T2T strategies.

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Literatur

  1. Smolen JS, Breedveld FC, Burmester GR et al (2016) Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann Rheum Dis 75:3–15

    Article  Google Scholar 

  2. Albrecht K, Luque Ramos A, Callhoff J et al (2018) Ambulante Versorgung und Krankheitslast der rheumatoiden Arthritis. Eine Analyse von Abrechnungsdaten und einer Versichertenbefragung. Z Rheumatol 77:102–112

    Article  CAS  Google Scholar 

  3. Micha R, Imamura F, Wyler von Ballmoos M et al (2011) Systematic review and meta-analysis of methotrexate use and risk of cardiovascular disease. Am J Cardiol 108:1362–1370

    Article  CAS  Google Scholar 

  4. Low ASL, Symmons DPM, Lunt M et al (2017) Relationship between exposure to tumour necrosis factor inhibitor therapy and incidence and severity of myocardial infarction in patients with rheumatoid arthritis. Ann Rheum Dis 76:654–660

    Article  CAS  Google Scholar 

  5. Radner H, Smolen JS, Aletaha D (2011) Comorbidity affects all domains of physical function and quality of life in patients with rheumatoid arthritis. Rheumatology 50:381–388

    Article  Google Scholar 

  6. Radner H, Yoshida K, al Frits Met (2015) The impact of multimorbidity status on treatment response in rheumatoid arthritis patients initiating disease-modifying anti-rheumatic drugs. Rheumatology 54:2076–2084

    Article  CAS  Google Scholar 

  7. Deutsches Rheumaforschungszentrum (2016) Kerndokumentation. Deutsches Rheumaforschungszentrum. Deutsches Rheumaforschungszentrum, Berlin (Daten noch unpubliziert)

    Google Scholar 

  8. England BR, Sayles H, Michaud K et al (2016) Cause-specific mortality in male US veterans with rheumatoid arthritis. Arthritis Care Res 68:36–45

    Article  Google Scholar 

  9. Ramos AL, Redeker I, Hoffmann F et al (2019) Comorbidities in patients with rheumatoid arthritis and their association with patient-reported outcomes: results of claims data linked to questionnaire survey. J Rheumatol. https://doi.org/10.3899/jrheum.180668

    Article  Google Scholar 

  10. Myasoedova E, Chandran A, Ilhan B et al (2016) The role of rheumatoid arthritis (RA) flare and cumulative burden of RA severity in the risk of cardiovascular disease. Ann Rheum Dis 75:560–565

    Article  CAS  Google Scholar 

  11. Meissner Y, Zink A, Kekow J et al (2016) Impact of disease activity and treatment of comorbidities on the risk of myocardial infarction in rheumatoid arthritis. Arthritis Res Ther 18:183

    Article  Google Scholar 

  12. Solomon DH, Reed GW, Kremer JM et al (2015) Disease activity in rheumatoid arthritis and the risk of cardiovascular events. Arthritis Rheum 67:1449–1455

    Article  CAS  Google Scholar 

  13. Myasoedova E, Chandran A, Ilhan B et al (2016) The role of rheumatoid arthritis (RA) flare and cumulative burden of RA severity in the risk of cardiovascular disease. Ann Rheum Dis 75:560–565

    Article  CAS  Google Scholar 

  14. Roubille C, Richer V, Starnino T et al (2015) The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis. Ann Rheum Dis 74:480–489

    Article  CAS  Google Scholar 

  15. Micha R, Imamura F, Wyler von Ballmoos M et al (2011) Systematic review and meta-analysis of methotrexate use and risk of cardiovascular disease. Am J Cardiol 108:1362–1370

    Article  CAS  Google Scholar 

  16. Rempenault C, Combe B, Barnetche T et al (2018) Metabolic and cardiovascular benefits of hydroxychloroquine in patients with rheumatoid arthritis: a systematic review and meta-analysis. Ann Rheum Dis 77:98–103

    Article  CAS  Google Scholar 

  17. Bartoloni E, Alunno A, Valentini V et al (2018) Targeting inflammation to prevent cardiovascular disease in chronic rheumatic diseases: myth or reality? Front Cardiovasc Med. https://doi.org/10.3389/fcvm.2018.00177

    Article  PubMed  PubMed Central  Google Scholar 

  18. Dixon WG, Watson KD, Lunt M et al (2007) Reduction in the incidence of myocardial infarction in patients with rheumatoid arthritis who respond to anti-tumor necrosis factor alpha therapy: results from the British Society for Rheumatology Biologics Register. Arthritis Rheum 56:2905–2912

    Article  CAS  Google Scholar 

  19. Jin Y, Kang EH, Brill G et al (2018) Cardiovascular (CV) risk after initiation of Abatacept versus TNF inhibitors in rheumatoid arthritis patients with and without baseline CV disease. J Rheumatol 45:1240–1248

    Article  CAS  Google Scholar 

  20. Kim SC, Solomon DH, Rogers JR et al (2018) No difference in cardiovascular risk of tocilizumab versus abatacept for rheumatoid arthritis: a multidatabase cohort study. Semin Arthritis Rheum 48:399–405

    Article  CAS  Google Scholar 

  21. Krüger K, Nüßlein H (2019) Kardiovaskuläre Komorbiditäten bei rheumatoider Arthritis. Z Rheumatol. https://doi.org/10.1007/s00393-018-0584-5

    Article  PubMed  Google Scholar 

  22. Crowson CS, Rollefstad S, Ikdahl E et al (2018) Impact of risk factors associated with cardiovascular outcomes in patients with rheumatoid arthritis. Ann Rheum Dis 77:48–54

    Article  CAS  Google Scholar 

  23. Primdahl J, Clausen J, Hørslev-Petersen K (2013) Results from systematic screening for cardiovascular risk in outpatients with rheumatoid arthritis in accordance with the EULAR recommendations. Ann Rheum Dis 72:1771–1776

    Article  CAS  Google Scholar 

  24. Van den Oever IAM, Heslinga M, Griep EN et al (2017) Cardiovascular risk management in rheumatoid arthritis patients still suboptimal: the implementation of cardiovascular risk management in rheumatoid arthritis project. Baillieres Clin Rheumatol 56:1472–1478

    Google Scholar 

  25. Veldhuijzen van Zanten JJCS, Sandoo A, Metsios GS et al (2019) Comparison of the effects of exercise and anti-TNF treatment on cardiovascular health in rheumatoid arthritis: results from two controlled trials. Rheumatol Int 39:219–225

    Article  CAS  Google Scholar 

  26. Wang S, He Q, Shuai Z (2018) Risk of serious infections in biological treatment of patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis: a meta-analysis. Clin Rheumatol 37:439–450

    Article  Google Scholar 

  27. Doran MF, Crowson CS, Pond GR, O’Fallon WM, Gabriel SE (2002) Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study. Arthritis Rheum 46:2287–2293

    Article  Google Scholar 

  28. Flossmann O, Berden A, de Groot K, Hagen C, Harper L, Heijl C, Höglund P, Jayne D, Luqmani R, Mahr A, Mukhtyar C, Pusey C, Rasmussen N, Stegeman C, Walsh M, Westman K, European Vasculitis Study Group. (2011) Long-term patient survival in ANCA-associated vasculitis. Ann Rheum Dis 70:488–494

    Article  Google Scholar 

  29. Jones RB, Tervaert JW, Hauser T, Luqmani R, Morgan MD, Peh CA, Savage CO, Segelmark M, Tesar V, van Paassen P, Walsh D, Walsh M, Westman K, Jayne DR, European Vasculitis Study Group (2010) Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med 363:211–220

    Article  CAS  Google Scholar 

  30. Feldman CH, Hiraki LT, Winkelmayer WC et al (2015) Serious infections among adult Medicaid beneficiaries with systemic lupus erythematosus and lupus nephritis. Arthritis Rheumatol 67:1577–1585

    Article  Google Scholar 

  31. Khanna D, Denton CP, Lin CJF, van Laar JM, Frech TM, Anderson ME, Baron M, Chung L, Fierlbeck G, Lakshminarayanan S, Allanore Y, Pope JE, Riemekasten G, Steen V, Müller-Ladner U, Spotswood H, Burke L, Siegel J, Jahreis A, Furst DE (2018) Safety and efficacy of subcutaneous tocilizumab in systemic sclerosis: results from the open-label period of a phase II randomised controlled trial (faSScinate). Ann Rheum Dis 77:212–220

    Article  CAS  Google Scholar 

  32. Kohn A, Meddi P (2012) How to manage IBD in patients with infections or malignancies? Dig Dis 30:420–424

    Article  Google Scholar 

  33. Winthrop KL, Baddley JW (2018) Pneumocystis and glucocorticoid use: to prophylax or not to prophylax (and when?); that is the question. Ann Rheum Dis 77:631–633

    Article  CAS  Google Scholar 

  34. Lal H, Cunningham AL, Godeaux O, Chlibek R, Diez-Domingo J, Hwang SJ, Levin MJ, McElhaney JE, Poder A, Puig-Barberà J, Vesikari T, Watanabe D, Weckx L, Zahaf T, Heineman TC, ZOE-50 Study Group. (2016) Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. N Engl J Med 372:2087–2096

    Article  Google Scholar 

  35. Wijetilleka S, Jayne DR, Mukhtyar C et al (2019) Recommendations for the management of secondary hypogammaglobulinaemia due to B cell targeted therapies in autoimmune rheumatic diseases. Rheumatology. https://doi.org/10.1093/rheumatology/key394

    Article  PubMed  Google Scholar 

  36. Singh JA, Cameron C, Noorbaloochi S et al (2015) Risk of serious infection in biological treatment of patients with rheumatoid arthritis: a systematic review and meta-analysis. Lancet 386:258–265

    Article  Google Scholar 

  37. Dixon WG, Abrahamowicz M, Beauchamp ME, Ray DW, Bernatsky S, Suissa S, Sylvestre MP (2012) Immediate and delayed impact of oral glucocorticoid therapy on risk of serious infection in older patients with rheumatoid arthritis: a nested case-control analysis. Ann Rheum Dis 71:1128–1133

    Article  CAS  Google Scholar 

  38. Stone JH, Tuckwell K, Dimonaco S et al (2017) Trial of tocilizumab in giant-cell arteritis. N Engl J Med 27:317–328

    Article  Google Scholar 

  39. Matcham F, Davies R, Hotopf M et al (2018) The relationship between depression and biologic treatment response in rheumatoid arthritis: An analysis of the British Society for Rheumatology Biologics Register. Rheumatology 57:835–843

    Article  Google Scholar 

  40. Inanc N, Yilmaz-Oner S, Can M et al (2014) The role of depression, anxiety, fatigue, and fibromyalgia on the evaluation of the remission status in patients with rheumatoid arthritis. J Rheumatol 41:1755–1760

    Article  Google Scholar 

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Authors and Affiliations

  1. Rheumatologisches Praxiszentrum, St. Bonifatius Str. 5, 81541, München, Deutschland

    K. Krüger

  2. Rheumatologische Facharztpraxis Schwerin, Schwerin, Deutschland

    C. Kneitz

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Correspondence to K. Krüger.

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K. Krüger: Honorare für Fortbildung/Beratung von folgenden Firmen: AbbVie, BMS, Biogen, Hexal, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche, Sanofi, UCB. C. Kneitz: Honorare für Fortbildung/Beratung von folgenden Firmen: AbbVie, Berlin Chemie, BMS, Celgene, Chugai, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi, UCB.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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M. Schneider, Düsseldorf

G.-R. Burmester, Berlin

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Krüger, K., Kneitz, C. Komorbiditäten – ihre Rolle im Treat-to-Target-Konzept für die rheumatoide Arthritis. Z Rheumatol 78, 422–428 (2019). https://doi.org/10.1007/s00393-019-0637-4

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