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German guidelines for the sequential medical treatment of rheumatoid arthritis with traditional and biologic disease-modifying antirheumatic drugs

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Abstract

The German Society of Rheumatology approved new German guidelines for the sequential medical treatment of rheumatoid arthritis (RA) based on the European League Against Rheumatism (EULAR) recommendations for the management of RA published in 2010. An update of the EULAR systematic literature research was performed in Medline, Embase, and Cochrane databases. Meta-analyses, controlled trials, cohort studies, and registry data addressing traditional and biologic disease-modifying antirheumatic drugs, glucocorticoids, and treatment strategies published between January 2009 and August 2011 were included. Two reviewers independently evaluated and compared the additional data that had been published after the time limit set by the EULAR recommendations. A national guideline working group developed an adapted set of recommendations. The new German guidelines were accepted by vote using an informal Delphi approach. Twelve recommendations and the resulting updated treatment algorithm were developed and approved as a practical orientation for rheumatologists. These recommendations are based on a successive treatment with traditional and biologic disease-modifying drugs depending on the individual progress of the disease and distinct patient characteristics. The German guidelines have been developed on the basis of the internationally well-recognized EULAR recommendations. In addition, more recent evidence from a systematic literature research was considered. They have been developed and approved by a group of national experts aiming at guidance for rheumatologists to reach best medical practice.

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References

  1. Smolen JS, Landewe R, Breedveld FC et al (2010) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis 69:964–975

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Nam JL, Winthrop KL, van Vollenhoven RF et al (2010) Current evidence for the management of rheumatoid arthritis with biological disease-modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of RA. Ann Rheum Dis 69:976–986

    Article  CAS  PubMed  Google Scholar 

  3. Gaujoux-Viala C, Smolen JS, Landewe R et al (2010) Current evidence for the management of rheumatoid arthritis with synthetic disease-modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis 69:1004–1009

    Article  CAS  PubMed  Google Scholar 

  4. Gorter SL, Bijlsma JW, Cutolo M et al (2010) Current evidence for the management of rheumatoid arthritis with glucocorticoids: a systematic literature review informing the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis 69:1010–1014

    Article  CAS  PubMed  Google Scholar 

  5. Knevel R, Schoels M, Huizinga TWJ et al (2010) Current evidence for a strategic approach to the management of rheumatoid arthritis with disease-modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis 69:987–994

    Article  CAS  PubMed  Google Scholar 

  6. Krüger K, Wollenhaupt J, Albrecht K et al (2012) German 2012 guidelines for the sequential medical treatment of rheumatoid arthritis. Adapted EULAR recommendations and updated treatment algorithm. [Article in German]. Z Rheumatol 71:592–603

    Article  PubMed  Google Scholar 

  7. Albrecht K, Krüger K, Müller-Ladner U, Wollenhaupt J (2012) Systematic literature research for S1 guidelines on sequential medical treatment of rheumatoid arthritis [Article in German]. Z Rheumatol 71:604–618

    Article  CAS  PubMed  Google Scholar 

  8. Wollenhaupt J, Albrecht K, Krüger K, Müller-Ladner U (2013) The new 2012 German recommendations for treating rheumatoid arthritis: differences compared to the European standpoint. Z Rheumatol 72(1):6–9

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Schoels M, Wong J, Scott DL et al (2010) Economic aspects of treatment options in rheumatoid arthritis: a systematic literature review informing the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis 69:996–1004

    Google Scholar 

  10. OCEBM Levels of Evidence Working Group* “The Oxford 2011 Levels of Evidence”. Oxford Centre for Evidence-Based Medicine. http://www.cebm.net/index.aspx?o=5653

  11. Wollenhaupt J, Alten R, Backhaus M et al (2009) Recommendations for the treatment of rheumatoid arthritis. Results from a German consensus conferenence: update 2009 [Article in German]. Akt Rheumatol 34:234–239

    Article  Google Scholar 

  12. Visser K, van der Heijde D (2009) Optimal dosage and route of administration of methotrexate in rheumatoid arthritis: a systematic review of the literature. Ann Rheum Dis 68:1094–1099

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Tarner IH, Manger B, Fleck E et al (2009) Evidence-based recommendations of a National Group of Experts on the use of methotrexate in inflammatory rheumatic diseases [Article in German]. Akt Rheum 34:59–66

    Article  Google Scholar 

  14. Bathon J, Robles M, Ximenes AC (2011) Sustained disease remission and inhibition of radiographic progression in methotrexate-naïve patients with rheumatoid arthritis and poor prognostic factors treated with abatacept: 2-year outcomes. Ann Rheum Dis 70:1949–1956

    Article  CAS  PubMed  Google Scholar 

  15. Smolen JS, Fleischmann R, Emery P et al (2011) The OPTIMA study of methotrexate and adalimumab: 78-week outcomes in early rheumatoid arthritis patients based on achieving a low DAS28 target after 26 weeks. Ann Rheum Dis 70(Suppl3):259

    Google Scholar 

  16. Soubrier M, Puéchal X, Sibilia J et al (2009) 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 48:1429–1434

    Article  CAS  PubMed  Google Scholar 

  17. De Boer KV, Visser K, Ronday HK et al (2010) Induction therapy with methotrexate and prednisone in rheumatoid or very early arthritic disease: IMPROVED study. Arthritis Rheum 62(Suppl10):1396

    Google Scholar 

  18. Klarenbeek NB, Güler-Yüksel M, van der Kooij SM et al (2011) The impact of four dynamic, goal-steered treatment strategies on the 5-year outcomes of rheumatoid arthritis patients in the BeSt study. Ann Rheum Dis 70:1039–1046

    Article  PubMed  Google Scholar 

  19. Hafstrem I, Albertsson K, Boonen A, van der Heijde D, Landewe R, Svensson B (2009) Remission achieved after 2 years treatment with low-dose prednisolone in addition to disease-modifying anti-rheumatic drugs in early rheumatoid arthritis is associated with reduced joint destruction still present after 4 years: an open 2-year continuation study. Ann Rheum Dis 68:508–513

    Article  Google Scholar 

  20. Todoerti M, Scire CA, Boffini N et al (2010) Early disease control by low-dose prednisone comedication may affect the quality of remission in patients with early rheumatoid arthritis. Ann NY Acad Sci 1193:139–145

    Article  CAS  PubMed  Google Scholar 

  21. Kremer JM, Genovese MC, Cannon GW (2002) Concomitant leflunomide therapy in patients with active rheumatoid arthritis despite stable doses of methotrexate. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 137:726–733

    Article  CAS  PubMed  Google Scholar 

  22. O’Dell JR, Leff R, Paulsen G (2002) Treatment of rheumatoid arthritis with methotrexate and hydroxychloroquine, methotrexate and sulfasalazine, or a combination of the three medications: results of a two-year, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 46:1164–1170

    Article  PubMed  Google Scholar 

  23. Tugwell P, Pincus T, Yocum D et al (1995) Combination therapy with cyclosporine and methotrexate in severe rheumatoid arthritis. The methotrexate-cyclosporine combination study group. N Engl J Med 333:137–141

    Article  CAS  PubMed  Google Scholar 

  24. Curtis JR, Yang S, Chen L et al (2012) Predicting low disease activity and remission using early treatment response to antitumour necrosis factor therapy in patients with rheumatoid arthritis: exploratory analyses from the TEMPO trial. Ann Rheum Dis 71:206–212

    Google Scholar 

  25. Haraoui B, Emery P, Mozaffarian N et al (2010) Change in CRP at 12 weeks predicts the risk of rapid radiographic progression at 2 years in methotrexate-treated patients with early rheumatoid arthritis. Arthritis Rheum 62(Suppl 10):110

    Google Scholar 

  26. Ichikawa Y, Saito T, Yamanaka H et al (2010) Clinical activity after 12 weeks of treatment with nonbiologics in early rheumatoid arthritis may predict articular destruction 2 years later. J Rheumatol 37:723–729

    Article  PubMed  Google Scholar 

  27. Singh JA, Christensen R, Wells GA (2009) Biologics for rheumatoid arthritis: an overview of Cochrane reviews. Cochrane Database Syst Rev 4 Wiley, Ltd, Chichester, doi:10.1002/14651858.CD007848

  28. Devine EB, Alfonso-Cristancho R, Sullivan SD (2011) Effectiveness of biologic therapies for rheumatoid arthritis: an indirect comparison approach. Pharmacotherapy 31:39–51

    Article  CAS  PubMed  Google Scholar 

  29. Salliot C, Finckh A, Katchamart W et al (2011) Indirect comparisons of the efficacy of biological antirheumatic agents in rheumatoid arthritis in patients with an inadequate response to conventional disease-modifying antirheumatic drugs or to an anti-tumour necrosis factor agent: a meta-analysis. Ann Rheum Dis 70:266–271

    Article  CAS  PubMed  Google Scholar 

  30. Dougados M, Huizinga T, Sheeran T et al (2011) Tocilizumab plus methotrexate does not have superior clinical efficacy to TCZ alone in RA patients with inadequate response to MTX: 24-week results of the ACT-RAY study. Ann Rheum Dis 70(Suppl3):73

    Google Scholar 

  31. Sibilia J, Graninger W, Östör A et al (2011) Comparison of tocilizumab as monotherapy or with add-on DMARDs in patients with rheumatoid arthritis and an inadequate response to previous treatments: ACT-SURE results. Ann Rheum Dis 70(Suppl3):466

    Google Scholar 

  32. Finckh A, Dehler S, Gabay C et al (2009) The effectiveness of leflunomide as a co-therapy of tumour necrosis factor inhibitors in rheumatoid arthritis: a population-based study. Ann Rheum Dis 68:33–39

    Article  CAS  PubMed  Google Scholar 

  33. Strangfeld A, Hierse F, Kekow J et al (2009) Comparative effectiveness of tumour necrosis factor alpha inhibitors in combination with either methotrexate or leflunomide. Ann Rheum Dis 68:1856–1862

    Article  CAS  PubMed  Google Scholar 

  34. Chatzidionysiou K, Lie E, Nasonov E et al (2012) Effectiveness of disease-modifying antirheumatic drug co-therapy with methotrexate and leflunomide in rituximab-treated rheumatoid arthritis patients: results of a 1-year follow-up study from the CERERRA collaboration. Ann Rheum Dis 71:374–377

    Article  CAS  PubMed  Google Scholar 

  35. Navarro-Sarrabia F, Ruiz-Montesinos D, Hernandez B et al (2009) DAS-28-based EULAR response and HAQ improvement in rheumatoid arthritis patients switching between TNF antagonists. BMJ Muskuloskelet Disord 10:91

    Article  Google Scholar 

  36. Keystone E, Ogale S, Devenport J, Lepley D (2011) Benefit of continuing tocilizumab therapy (8 mg/kg every 4 weeks) in rheumatoid arthritis patients who have not responded adequately within the first 8 weeks. Ann Rheum Dis 70(Suppl3):461

    Google Scholar 

  37. Kievit W, Fransen J, Adang EM et al (2011) Long-term effectiveness and safety of TNF-blocking agents in daily clinical practice: results from the Dutch Rheumatoid Arthritis Monitoring register. Rheumatology 50:196–203

    Article  CAS  PubMed  Google Scholar 

  38. Schiff M, Beaulieu A, Scott DL, Rashford M (2010) Mycophenolate mofetil in the treatment of adults with advanced rheumatoid arthritis: three 24-week, randomized, double-blind, placebo- or ciclosporin-controlled trials. Clin Drug Investig 30:613–624

    Article  CAS  PubMed  Google Scholar 

  39. Tanaka Y, Takeuchi T, Mimori T et al (2010) Discontinuation of infliximab 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 

  40. 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  PubMed  Google Scholar 

  41. O’Mahony R, Richards A, Deighton C, Scott D (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  PubMed  Google Scholar 

  42. Tiippana-Kinnunen T, Paimela L, Kautiainen H, Laasonen L, Leirisalo-Repo M (2010) Can disease-modifying anti-rheumatic drugs be discontinued in long-standing rheumatoid arthritis? A 15-year follow-up. Scand J Rheumol 39:12–18

    Article  CAS  Google Scholar 

  43. Smolen JS, Aletaha D, Koeller M, Weisman MH, Emery P (2007) New therapies for treatment of rheumatoid arthritis. Lancet 370:1861–1874

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The German Society of Rheumatology financed the systematic literature search and the consensus meeting. It was supported by an unrestricted Grant “of the corporate members: Abbvie GmbH & Co.KG, Chugai Pharma Marketing Ltd., Pfizer Pharma GmbH, Roche Pharma AG, Sanofi-Aventis Deutschland GmbH, UCB Pharma GmbH.” The corresponding author points out that financial support had no impact on the content of the guidelines.

Conflict of interest

Dr. Albrecht reports grants from German Society of Rheumatology, during the conduct of the study; personal fees from Abbvie GmbH, outside the submitted work; and on behalf of all co-authors, the corresponding authors declares the following conflicts of interests: E.G.-I. declares that she has no potential conflicts of interests. The following authors declare a potential conflict of interest having received grant support and/or honoria for consultations, presentations, and/or travel expenses: K.A.: Abbvie; R.A.: Abbvie, BMS, GSK, Lilly, Mundipharma, Novartis, Pfizer, Roche, UCB; M.B.: Abbvie, BMS, MSD, Pfizer, Roche, UCB; C.B.: Abbvie, Amgen, GSK, Genzyme, MSD, Pfizer, Roche, Shire, Sanofi-Aventis; W.B.: AstraZeneca, MSD; J.B.: Abbvie, BMS, MSD, Mundipharma, Novartis, Pfizer, Roche, UCB, H.B.: Abbvie, BMS, Roche, Pfizer, UCB, Chugai, Amgen, Novartis, Morphosys, Celgene, Sanovi Aventis; G.R.B.: Abbvie, BMS, MSD, Pfizer, Roche, UCB; M.G.: Abbvie, Amgen, BMS, Chugai, Hexal, Merck, MSD, Mundipharma, Pfizer, Roche, SOBI und UCB; A.G.: Abbott, Chugai, MSD, Roche, UCB; H.K.: Abbvie, BMS, Chugai, Medac, MSD, Novartis, Pfizer, Roche, UCB; J.K.: Abbvie, Actelion, Berlin-Chemie, BMS, Chugai, GSK/HGS, Medac, Merck, MSD, Pfizer, Roche, Sanofi-Aventis, UCB; A.K.: Abbvie, BMS, Chugai, MSD, Pfizer, Roche, UCB; K.K.: Abbvie, BMS, MSD, Mundipharma, Pfizer, UCB, Roche; H.M.L.: Abbvie, Bristol-Myers Squibb, Chugai, GSK, Medac, Merck, MSD, Novartis, Pfizer, Roche, Sanofi-Aventis, UCB; B.M.: Abbvie, Berlin-Chemie, BMS, Biomarin, Chugai, Genzyme, GSK, MSD, Novartis, Nycomed, Pfizer, SOBI, UCB; U.M.L.: Abbvie, BMS, Chugai, MSD, Pfizer, Roche, UCB; H.N.: Abbvie, BMS, Chugai, Essex, Merck, MSD, Mundipharma, Pfizer, Roche, UCB, Wyeth; H.-G. P.: Abbvie, BMS, MSD, Pfizer und UCB; A.R.: Abbvie, BMS, Chugai, MSD, Novartis, Pfizer, Roche, UCB; C.S.: Abbvie, Chugai, GSK, MSD, Novartis, Pfizer, Roche, UCB, Wyeth; M.S.: Abbvie, Chugai, MSD, Pfizer, Roche, UCB; H.S.-K.: Abbvie, Actelion, Astra-Zeneca, Biotest, BMS, Chugai, Essex, Gilead, GSK, HGS, MSD, Medac, Merck, Mundai Pharma, Novartis, Nycomed, Savient, Pfizer, Roche, UCB, Wyeth; H.P.T.: Abbvie, BMS, Chugai, MSD, Roche; J.W.: Abbvie, BMS, Chugai, MSD, Pfizer, Roche, UCB. S.W.: Abbvie, Chugai, MSD, Novartis, Pfizer, Roche, UCB.

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Authors and Affiliations

  1. German Society of Rheumatology, Berlin, Germany

    Katinka Albrecht

  2. Centre of Rheumatology, Munich, Germany

    Klaus Krüger

  3. Rheumatologikum, Schoen Hospital, Hamburg, Germany

    Jürgen Wollenhaupt

  4. Department of Internal Medicine, Rheumatology, Schlosspark-Clinic, University Medicine Berlin, Berlin, Germany

    Rieke Alten

  5. Department of Rheumatology and Clinical Immunology, Charité University Medicine Berlin, Free University and Humboldt University, Berlin, Germany

    Marina Backhaus & Gerd R. Burmester

  6. Department of Rheumatology and Gerontology, University of Leipzig, Leipzig, Germany

    Christoph Baerwald

  7. Department of Internal Medicine and Rheumatology, Klaus Miehlke Hospital, Wiesbaden, Germany

    Wolfgang Bolten

  8. Centre of Rheumatology Ruhr, St. Josef Hospital, Herne, Germany

    Jürgen Braun

  9. Department of Rheumatology, Johann Wolfgang Goethe University, Frankfurt Main, Germany

    Harald Burkhardt

  10. Interdisciplinary Diagnostic and Therapy, WWU, Münster, Germany

    Markus Gaubitz

  11. Centre of Rheumatology and Autoimmunology, Hamburg, Germany

    Angela Gause

  12. German League Against Rheumatism, Bonn, Germany

    Erika Gromnica-Ihle

  13. Practice for Rheumatology and Gastroenterology and Head of the Department of Rheumatology Hospital Neuwittelsbach, Munich, Germany

    Herbert Kellner

  14. Department of Internal Rheumatology, Red Cross Hospital, Bremen, Germany

    Jens Kuipers

  15. Department of Rheumatology, Immanuel Hospital, Berlin-Buch, Berlin, Germany

    Andreas Krause

  16. Division of Rheumatology, Department of Medicine V, University of Heidelberg, Heidelberg, Germany

    Hans-Martin Lorenz

  17. Department of Rheumatology, University of Erlangen, Erlangen, Germany

    Bernhard Manger

  18. Practice of Internal Rheumatology, Nuremberg, Germany

    Hubert Nüßlein

  19. Practice of Rheumatology, Physical Therapy and Clinical Immunology, Hannover, Germany

    Hans-Georg Pott

  20. Department of Immunology and Rheumatology, University of Cologne, Cologne, Germany

    Andrea Rubbert-Roth

  21. Department of Rheumatology, Heinrich-Heine-University, Düsseldorf, Germany

    Matthias Schneider

  22. Department of Rheumatology and Clinical Immunology, Kliniken Essen Süd, Essen, Germany

    Christof Specker

  23. Division of Rheumatology and Clinical Immunology, Med. Klinik und Poliklinik IV, LMU München, Munich, Germany

    Hendrik Schulze-Koops

  24. Department of Rheumatology and Clinical Immunology, University of Wurzburg, Würzburg, Germany

    Hans-Peter Tony

  25. Evangelisches Fachkrankenhaus Ratingen, Rheumatologie, Ratingen, Germany

    Siegfried Wassenberg

  26. Department of Rheumatology and Clinical Immunology, Justus-Liebig University, Giessen, Kerckhoff Klinik, Bad Nauheim, Germany

    Ulf Müller-Ladner

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  1. Katinka Albrecht
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  2. Klaus Krüger
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  3. Jürgen Wollenhaupt
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  5. Marina Backhaus
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  6. Christoph Baerwald
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  7. Wolfgang Bolten
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  8. Jürgen Braun
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  9. Harald Burkhardt
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  10. Gerd R. Burmester
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  11. Markus Gaubitz
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  12. Angela Gause
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  13. Erika Gromnica-Ihle
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  14. Herbert Kellner
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  15. Jens Kuipers
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  16. Andreas Krause
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  17. Hans-Martin Lorenz
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  18. Bernhard Manger
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  19. Hubert Nüßlein
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  20. Hans-Georg Pott
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  21. Andrea Rubbert-Roth
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  22. Matthias Schneider
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  23. Christof Specker
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  24. Hendrik Schulze-Koops
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  25. Hans-Peter Tony
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  26. Siegfried Wassenberg
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  27. Ulf Müller-Ladner
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Correspondence to Katinka Albrecht.

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Albrecht, K., Krüger, K., Wollenhaupt, J. et al. German guidelines for the sequential medical treatment of rheumatoid arthritis with traditional and biologic disease-modifying antirheumatic drugs. Rheumatol Int 34, 1–9 (2014). https://doi.org/10.1007/s00296-013-2848-3

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  • DOI: https://doi.org/10.1007/s00296-013-2848-3

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