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Therapieabbau bei stabil eingestellter rheumatoider Arthritis

Stand des Wissens

Treatment reduction in well-controlled rheumatoid arthritis

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Zusammenfassung

Die Qualität heutiger Behandlungsmöglichkeiten für die rheumatoide Arthritis (RA) hat zu hochgesteckten Therapiezielen wie Remission geführt, die in vielen Fällen auch erreicht werden. Patientenwünschen entsprechend, aber auch aus ökonomischen Gründen wird vermehrt die Möglichkeit diskutiert, nach Erreichen des Therapieziels die Behandlung zu reduzieren und letztlich sogar versuchsweise abzusetzen („drug-free remission“). Zunehmend zeigen Studienergebnisse, dass in etwa 30–60 % der Fälle ein solches Vorgehen zumindest für einige Zeit erfolgreich ist. Da erneute Therapie im Fall eines Flare fast immer gelingt, ist das Risiko eines solchen Vorgehens gering – sofern eine Überwachung des Patienten nach Reduktion bzw. Absetzen sicher gewährleistet ist. Bisher gibt es keine Belege dafür, dass die Strategie des kontrollierten Therapieabbaus ein Risiko für ungünstige Langzeitfolgen beinhaltet. Als Reihenfolge für das Vorgehen empfehlen gegenwärtig die Leitlinien, zuerst das Glukokortikoid abzusetzen, anschließend das Biologikum zu reduzieren, ggf. später abzusetzen, schließlich bei anhaltender Remission ähnlich mit dem synthetischen DMARD („disease modifying antirheumatic drug“; in der Regel Methotrexat) zu verfahren. Eine Reihe von Voraussetzungen scheint den Erfolg der Therapiereduktion zu begünstigen wie eher niedrige Krankheitsaktivität zu Beginn, Seronegativität sowie insbesondere kurze Krankheitsdauer bei Therapiebeginn. Die Entscheidung zum Abbau muss von Arzt und Patient gemeinsam getroffen werden, eine stabile Einstellung der RA sollte mindestens seit 6 Monaten bestehen.

Abstract

Nowadays, the excellent treatment options available for rheumatoid arthritis (RA) result in ambitious therapeutic goals, such as remission, which can actually be achieved for many RA patients. In a state of sustained remission many patients request reduction in drug treatment and this as well as economic reasons makes treatment reduction or even drug-free remission a reasonable target. Increasingly successful reduction of disease-modifying antirheumatic drug (DMARD) treatment has been shown in studies for approximately 30–60 % of patients in sustained remission, at least for some period of time. Because flare retreatment is successful in nearly all cases, the risk of treatment de-escalation can be minimized, so long as patients are continuously monitored after reduction or termination of drug treatment. No study has yet shown an elevated risk for unfavorable long-term outcome in cases of controlled treatment reduction. Current treatment recommendations are that glucocorticoids should first be withdrawn followed by reduction and termination of biologics and in cases of sustained remission finally, conventional DMARDs, such as methotrexate should be reduced and possibly terminated to achieve the defined target of drug-free remission. Factors facilitating success of tapering antirheumatic drugs are low disease activity at initiation, negative serological tests and short disease duration after starting DMARD treatment. A joint decision between rheumatologists and patients as well as continuous remission for at least 6 months are prerequisites for drug reduction.

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Literatur

  1. Allaart CF, Lems WF, Huizinga TWJ (2013) The BeSt way of withdrawing biologic agents. Clin Exp Rheumatol 31(Suppl 78):S14–S18

    CAS  PubMed  Google Scholar 

  2. Brocq O, Millasseau E, Albert C et al (2009) Effect of discontinuing TNFa antagonist therapy in patients with remission of rheumatoid arthritis. Joint Bone Spine 76:350–355

    Article  CAS  PubMed  Google Scholar 

  3. Detert J, Bastian H, Listing J et al (2013) Induction therapy with adalimumab plus methotrexate for 24 weeks followed by methotrexate monotherapy up to week 48 versus methotrexate therapy alone for DMARD-naïve patients with early rheumatoid arthritis: HIT HARD, an investigator-initiated study. Ann Rheum Dis 72:844–850

    Article  CAS  PubMed  Google Scholar 

  4. Emery P, Hammoudeh M, FitzGerald O et al (2014) Sustained remission with etanercept tapering in early rheumatoid arthritis. N Engl J Med 371:1781–1792

    Article  CAS  PubMed  Google Scholar 

  5. Emery P, Burmester GR, Bykerk VP et al (2015) Evaluating drug-free remission with abatacept in early rheumatoid arthritis: results from the phase 3b, multicentre, randomised, active-controlled AVERT study of 24 months, with a 12-month, double-blind treatment period. Ann Rheum Dis 74:19–26

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Haschka J, Englbrecht M, Hueber AJ et al (2015) Relapse rates in patients with rheumatoid arthritis in stable remission tapering or stopping antirheumatic therapy: interim results from the prospective randomised controlled RETRO study. Ann Rheum Dis (online first Feb 6, 10.1136/annrheumdis-2014-206439)

  7. Huizinga TWJ, Conaghan PG, Martin-Mola E et al (2015) Clinical and radiographic outcomes at 2 years and the effect of tocilizumab discontinuation following sustained remission in the second and third year of the ACT-RAY study. Ann Rheum Dis 74:35–43

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Iwamoto T, Ikeda K, Hosokawa J et al (2014) Prediction of relapse after discontinuation of biologic agents by ultrasonographic assessment in patients with rheumatoid arthritis in clinical remission: high predictive values of total gray-scale and power Doppler scores that represent residual synovial inflammation before discontinuation. Arthritis Care Res 66:1576–1581

    Article  Google Scholar 

  9. Krüger K, Wollenhaupt J, Albrecht K et al (2012) S1-Leitlinie der DGRh zur sequenziellen medikamentösen Therapie der rheumatoiden Arthritis 2012: adaptierte EULAR Empfehlungen und aktualisierter Therapiealgorithmus. Z Rheumatol 71:592–603

    Article  PubMed  Google Scholar 

  10. Marks JL, Holroyd CR, Dimitrov BD et al (2015) Does combined clinical and ultrasound assessment allow selection of individuals with rheumatoid arthritis for sustained reduction of anti-TNF therapy? Arthritis Care Res. doi:10.1002/acr.22552

  11. O’Mahony R, Richards A, Deighton C et al (2010) Withdrawal of disease-modifying antirheumatic drugs in patients with rheumatoid arthritis: a systematic review and meta-analysis. Ann Rheum Dis 69:1823–1826

    Article  Google Scholar 

  12. Pope JE, Haraoui B, Thorne JC et al (2014) The Canadian Methotrexate and Etanercept Outcome Study: a randomised trial of discontinuing versus continuing methotrexate after 6 months of etanercept and methotrexate therapy in rheumatoid arthritis. Ann Rheum Dis 73:2144–2151

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Quinn MA, Conaghan PG, O’Connor PJ et al (2005) Very early treatment with infliximab in addition to methotrexate in early, poor-prognosis rheumatoid arthritis reduces magnetic resonance imaging evidence of synovitis and damage, with sustained benefit after infliximab withdrawal. Arthritis Rheum 52:27–35

    Article  CAS  PubMed  Google Scholar 

  14. Raffeiner B, Botsios C, Ometto F et al (2015) Effects of half dose etanercept (25 mg once a week) on clinical remission and radiographic progression in patients with rheumatoid arthritis in clinical remission achieved with standard dose. Clin Exp Rheumatol 33:63–68

    PubMed  Google Scholar 

  15. Saleem B, Keen H, Goeb V et al (2010) Patients with RA in remission on TNF blockers: when and in whom can TNF blocker therapy be stopped? Ann Rheum Dis 69:1636–1642

    Article  PubMed  Google Scholar 

  16. Smolen JS, Nasch P, Durez P et al (2013) Maintenance, reduction, or withdrawal of etanercept after treatment with etanercept and methotrexate in patients with moderate rheumatoid arthritis (PRESERVE): a randomised controlled trial. Lancet 381:918–929

    Article  CAS  PubMed  Google Scholar 

  17. Smolen JS, Emery P, Fleischmann R et al (2014) Adjustment of therapy in rheumatoid arthritis on the basis of achievement of stable low disease activity with adalimumab plus methotrexate or methotrexate alone: the randomised controlled OPTIMA trial. Lancet 383:321–332

    Article  CAS  PubMed  Google Scholar 

  18. Smolen JS, Landewé R, Breedveld FC et al (2014) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis 73:492–509

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Smolen JS, Emery P, Ferraccioli GF et al (2015) Certolizumab pegol in rheumatoid arthritis patients with low to moderate activity: the CERTAIN double-blind, randomised, placebo-controlled trial. Ann Rheum Dis 74:843–850

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Takeuchi T, Matsubara T, Ohta S et al (2015) Biologic-free remission of established rheumatoid arthritis after discontinuation of abatacept: a prospective, multicentre, observational study in Japan. Rheumatology 54:683–691

    Article  PubMed Central  PubMed  Google Scholar 

  21. Tanaka Y, Takeuchi T, Mimori T et al (2010) Discontinuation of infl iximab after attaining low disease activity in patients with rheumatoid arthritis: RRR (remission induction by Remicade in RA) study. Ann Rheum Dis 69:1286–1291

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Tanaka Y, Hirata S, Kubo S et al (2015) Discontinuation of adalimumab after achieving remission in patients with established rheumatoidarthritis: 1-year outcome of the HONOR study. Ann Rheum Dis 74:389–395

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Ten Wolde S, Breedveld FC, Hermans J et al (1996) Randomised placebo-controlled study of stopping second-line drugs in rheumatoid arthritis. Lancet 347:347–352

    Article  Google Scholar 

  24. Van der Maas A, Kievit W, Bernt JF van den et al (2012) Down-titration and discontinuation of infliximab in rheumatoid arthritis patients with stable low disease activity and stable treatment: an observational cohort study. Ann Rheum Dis 71:1849–1854

    Article  Google Scholar 

  25. Van der Nies JAB, Tsonaka R, Gaujoux-Viala C et al (2015) Evaluating relationships between symptom duration and persistence of rheumatoid arthritis: does a window of opportunity exist? Results on the Leiden Early Arthritis Clinic and ESPOIR cohorts. Ann Rheum Dis 74:806–812

    Article  Google Scholar 

  26. Van der Woude D, Young A, Jayakumar K et al (2009) Prevalence of and predictive factors for sustained disease-modifying antirheumatic drug-free remission in rheumatoid arthritis. Arthritis Rheum 60:2262–2271

    Article  Google Scholar 

  27. Van Herwaarden N, Herfkens-Hol S, Maas A van der et al (2014) Dose reduction of tocilizumab in rheumatoid arthritis patients with low disease activity. Clin Exp Rheumatol 32:390–394

    Google Scholar 

  28. Yamanaka H, Seto Y, Nagaoka S et al. (2014) Discontinuation of Etanercept in early rheumatoid arthritis patients who have achieved sustained remission: results of the randomized controlled trial in period 2 of the Entourage study. Ann Rheum Dis 73(Suppl):THU0169

    Article  Google Scholar 

  29. Yoshida K, Sung YK, Kavanaugh A et al (2014) Biologic discontinuation studies: a systematic review of methods. Ann Rheum Dis 73:595–599

    Article  PubMed  Google Scholar 

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Einhaltung ethischer Richtlinien

Interessenkonflikt. K. Krüger: Vorträge und Beratungstätigkeit für die Firmen Abbvie, BMS, Medac, MSD, Pfizer, Roche, UCB. E. Edelmann: Vorträge und Beratungstätigkeit für die Firmen Abbvie, BMS, MSD, Pfizer, Roche/Chugai, UCB.

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Krüger, K., Edelmann, E. Therapieabbau bei stabil eingestellter rheumatoider Arthritis. Z Rheumatol 74, 414–420 (2015). https://doi.org/10.1007/s00393-014-1534-5

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