Biologika für die frühe RA

Zusammenfassung

Der unmittelbare Beginn einer DMARD-Therapie nach Sicherung der Diagnose einer RA ist heute Standard. In der Regel wird die Therapie mit Methotrexat in Kombination mit Glucocorticoiden begonnen und bei Erfolglosigkeit durch eine DMARD-Kombination ersetzt. 5 Biologika, Infliximab, Etanercept, Adalimumab, Abatacept und Rituximab wurden bisher in Studien bei Früh-RA getestet und haben sich in Kombination mit Mtx als erfolgreich erwiesen. Im Standard-Algorithmus wird die Kombination Biologikum+Mtx bei Misserfolg einer DMARD-Kombination 6 Monate nach DMARD-Beginn angewendet. Ein Einsatz als Starttherapie hat hingegen in mehreren Strategie-Studien Vorteile im Vergleich zur DMARD-Kombinationstherapie nur radiologisch gezeigt. Ein früher Biologika-Einsatz (nach erfolgloser DMARD-Starttherapie) wird gleichwohl in den EULAR-Empfehlungen für Patienten mit Merkmalen einer ungünstigen Prognose nahegelegt, dieses Vorgehen ist jedoch bisher nicht durch Studien belegt – eine derartige Studie wäre dringend wünschenswert. Ein attraktives Konzept für die Zukunft könnte jedoch die Verwendung von Biologika+Mtx als Starttherapie mit dem Ziel sein, eine anhaltende medikamentenfreie Remission zu erreichen. Erste Studienresultate, z. B. in der BeST-Studie, belegen, dass dieses Konzept funktionieren könnte.

Abstract

DMARD treatment for early rheumatoid arthritis should today be started as soon as diagnosis is made. The combination of methotrexate (Mtx) and glucocorticoids is considered to be the first-line treatment followed by DMARD combinations in cases of a lack of success. 5 biologics, infliximab, etanercept, adalimumab, abatacept and rituximab, have been tested successfully in combination with Mtx in controlled early RA studies. Normally a biologic+Mtx should be the next step after lack of effect with DMARD combination, at least 6 months after starting DMARD treatment. Recently published EULAR recommendations consider a second step use of biologics after the first DMARD treatment has missed the target in cases with the presence of poor prognostic factors. This recommendation, however, is not evidence-based until now. Some recent studies, e. g., BeST suggest that a biologic+Mtx as starting regimen might induce long-lasting drug-free remission in many patients and so this could be an attractive concept for future.

Schlüsselwörter

frühe rheumatoide Arthritis - DMARDs - Biologika - medikamentenfreie Remission

Key words

early rheumatoid arthritis - DMARDs - biologics - drug-free remission

Literatur

• 1 Smolen JS, Landewé R, Breedveld FC. et al . EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs.  Ann Rheum Dis. 2010;  69: online May 5,2010
• 2 Schneider M, Lelgemann M, Abholz HH. et al .Interdisziplinäre Leitlinie Management der frühen rheumatoiden Arthritis.. Steinkopff-Verlag Darmstadt; 2006: 10
• 3 van der Linden MP, le Cessie S, Raza K. et al . Long-term impact of delay in assessment of patients with early arthritis.  Arthritis Rheum. 2010;  62 3537-3546
• 4 Manger B, Michels H, Nüsslein HG. et al und die Kommission Pharmakotherapie der DGRh: Neufassung der Empfehlungen der Kommission Pharmakotherapie der DGRh Therapie mit Tumornekrosefaktorhemmenden Wirkstoffen bei entzündlich-rheumatischen Erkrankungen.  Z Rheumatol. 2007;  66 72-75
• 5 Emery P, Van Vollenhoven R, Ostergaard M. et al . Guidelines for initiation of anti-tumour necrosis factor therapy in rheumatoid arthritis: similarities and differences across Europe.  Ann Rheum Dis. 2009;  68 456-459
• 6 Aletaha D. Therapy: Challenging the course of RA: time for drug-free remission?.  Nat Rev Rheumatol. 2010;  6 442-443
• 7 St Clair EW, van der Heijde DM, Smolen JS. et al . Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial.  Arthritis Rheum. 2004;  50 3432-3443
• 8 Smolen JS, Han C, van der Heijde DM. et al . Radiographic changes in rheumatoid arthritis patients attaining different disease activity states with methotrexate monotherapy and infliximab plus methotrexate: the impacts of remission and tumour necrosis factor blockade.  Ann Rheum Dis. 2009;  68 823-827
• 9 Quinn MA, Conaghan PG, O’Connor PJ. et al . 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: results from a twelve-month randomized, double-blind, placebo-controlled trial.  Arthritis Rheum. 2005;  52 27-35
• 10 Bejarano V, Conaghan PG, Quinn MA. et al . Benefits 8 years after a remission induction regime with an infliximab and methotrexate combination in early rheumatoid arthritis.  Rheumatology. 2010;  49 1971-1974
• 11 Durez P, Malghem J, Toukap AN. et al . Treatment of Early Rheumatoid Arthritis. A Randomized Magnetic Resonance Imaging Study Comparing the Effects of Methotrexate Alone, Methotrexate in Combination With Infliximab, and Methotrexate in Combination With Intravenous Pulse Methylprednisolone.  Arthritis Rheum. 2007;  56 3919-3927
• 12 Bathon JM, Martin RW, Fleischmann RM. et al . A comparison of Etanercept and Methotrexate in patients with early rheumatoid arthritis.  N Engl J Med. 2000;  343 1586-1593
• 13 Emery P, Breedveld FC, Hall S. et al . Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial.  Lancet. 2008;  372 375-382
• 14 Emery P, Breedveld F, van der Heijde D. et al . Two-year clinical and radiographic results with combination etanercept-methotrexate therapy versus monotherapy in early rheumatoid arthritis: a two-year, double-blind, randomized study.  Arthritis Rheum. 2010;  62 674-682
• 15 Breedveld FC, Weisman MH, Kavanaugh AF. et al . The PREMIER Study. A Multicenter, Randomized, Double-Blind Clinical Trial of Combination Therapy With Adalimumab Plus Methotrexate Versus Methotrexate Alone or Adalimumab Alone in Patients With Early, Aggressive Rheumatoid Arthritis Who Had Not Had Previous Methotrexate Treatment.  Arthritis Rheum. 2006;  54 26-37
• 16 Van der Heijde D, Breedveld FC, Kavanaugh A. et al . Disease activity, physical function, and radiographic progression after longterm therapy with adalimumab plus methotrexate: 5-year results of PREMIER.  J Rheumatol. 2010;  37 2237-2246
• 17 Bejarano V, Quinn M, Conaghan PG. et al . Effect of the Early Use of the Anti–Tumor Necrosis Factor Adalimumab on the Prevention of Job Loss in Patients With Early Rheumatoid Arthritis.  Arthritis Rheum. 2008;  59 1467-1474
• 18 Westhovens R, Robles M, Ximenes AC. et al . Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors.  Ann Rheum Dis. 2009;  68 1870-1877
• 19 Emery P, Durez P, Dougados M. et al . Impact of T-cell costimulation modulation in patients with undifferentiated inflammatory arthritis or very early rheumatoid arthritis: a clinical and imaging study of abatacept (the ADJUST trial).  Ann Rheum Dis. 2010;  69 510-516
• 20 Tak PP, Rigby WF, Rubbert-Roth A. Inhibition of joint damage and improved clinical outcomes with rituximab plus methotrexate in early active rheumatoid arthritis: the IMAGE trial.  Ann Rheum Dis. 2011;  70 39-46
• 21 Soubrier M, Puéchal X, Sibilia J. et al . Evaluation of two strategies (initial methotrexate monotherapy vs its combination with adalimumab) in management of early active rheumatoid arthritis: data from the GUEPARD trial.  Rheumatology. 2009;  48 1429-1434
• 22 Van Vollenhoven RF, Ernestam S, Geborek P. et al . Addition of infliximab compared with addition of sulfasalazine and hydroxychloroquine to methotrexate in patients with early rheumatoid arthritis (Swefot trial): 1-year results of a randomised trial.  Lancet. 2009;  374 459-466
• 23 Rezaei H, van Vollenhoven, Forslin K. et al . Radiological Progression in Patients with Early RA and a Good Clinical Response to Mtx Monotherapy: Predictors and Clinical Implications.  Arthritis Rheum. 2010;  62 (Suppl.) S578 (Abstr.1392)
• 24 Moreland LW, O’Dell JR, Paulus HE. et al . TEAR: Treatment of Early Aggressive RA; A Randomized, Double-Blind, 2-Year Trial Comparing Immediate Triple DMARD Versus MTX Plus Etanercept to Step-up From Initial MTX Monotherapy.  Arthritis Rheum. 2009;  60 (Suppl.) S 772 (Abstr.1895)
• 25 Moreland LW, O’Dell JR, Paulus HE. et al . Two-year Radiographic Results from the TEAR Trial.  Arthritis Rheum. 2010;  62 (Suppl.) S568 (Abstr.1368)
• 26 Van der Woude D, Young A, Jayakumar K. et al . Prevalence of and predictive factors for sustained disease-modifying antirheumatic drug-free remission in rheumatoid arthritis: results from two large early arthritis cohorts.  Arthritis Rheum. 2009;  60 2262-2271
• 27 Klarenbeek NB, van der Kooij SM, Güler-Yüksel M. et al . Discontinuing treatment in patients with rheumatoid arthritis in sustained clinical remission: exploratory analyses from the BeSt study.  Ann Rheum Dis. 2010;  Epub Nov 10.
• 28 Aletaha D, Neogi T, Silman AJ. et al . 2010 Rheumatoid Arthritis Classification Criteria. An American College of Rheumatology/European League Against Rheumatism Collaborative Initiative.  Arthritis Rheum. 2010;  62 2569-2581
• 29 Wollenhaupt J, Alten R, Backhaus M. et al . Aktualisiertes Therapieschema der Rheumatoiden Arthritis. Ergebnisse eines Konsensusprozesses deutscher Rheumatologen 2009.  Akt Rheumatol. 2009;  34 234-239
• 30 Hetland ML, Stengaard-Pedersen K, Junker P. et al . Combination treatment with methotrexate, cyclosporine, and intraarticular betamethasone compared with methotrexate and intraarticular betamethasone in early active rheumatoid arthritis: an investigator-initiated, multicenter, randomized, double-blind, parallel-group, placebo-controlled study.  Arthritis Rheum. 2006;  54 1401-1409
• 31 Visser K, Goekoop-Ruiterman YPM, de Vries-Bouwstra JK. et al . A matrix risk model for the prediction of rapid radiographic progression in patients with rheumatoid arthritis receiving different dynamic treatment strategies: post hoc analyses from the BeSt study.  Ann Rheum Dis. 2010;  69 1333-1337

Korrespondenzadresse