Zeitschrift für Rheumatologie

, Volume 78, Issue 9, pp 881–888 | Cite as

Rituximab in routine care of severe active rheumatoid arthritis

A prospective, non-interventional study in Germany
  • A. KrauseEmail author
  • P. M. Aries
  • S. Berger
  • C. Fiehn
  • H. Kellner
  • H.-M. Lorenz
  • L. Meier
  • G. A. Müller
  • U. Müller-Ladner
  • A. Schwarting
  • H.-P. Tony
  • M. A. Peters
  • J. Wendler



To assess safety, effectiveness and onset of effect of rituximab (RTX) in routine clinical treatment of severe, active rheumatoid arthritis (RA).


Prospective, multi-centre, non-interventional study in rheumatological outpatient clinics or private practices in Germany. RTX-naïve adult patients were to receive RTX according to marketing authorisation and at their physician’s discretion. Also according to their physician’s discretion, patients could receive a second cycle of RTX (re-treatment = treatment continuation). Major outcome was the change in Disease Activity Score based on 28-joints count and erythrocyte sedimentation rate (DAS28-ESR) over 24 weeks and during 6 months of re-treatment.


Overall, 1653 patients received at least one cycle RTX; 99.2% of these had received disease-modifying antirheumatic drugs (DMARD) pre-treatment and 75.5% anti-tumor necrosis factor(TNF)‑α pre-treatment. After a mean interval of 8.0 months, 820 patients received RTX re-treatment. Mean DAS28-ESR decreased from 5.3 at baseline to 3.8 after 24 weeks (−1.5 [95% confidence interval, CI: −1.6; −1.4]), and from 4.1 at start of cycle 2 to 3.5 at study end (change from baseline: −1.8 [95% CI: −2.0; −1.7]). Improvements in DAS28-ESR and Health Assessment Questionnaire (HAQ) score occurred mainly during the first 12 weeks of RTX treatment, with further DAS28-ESR improvement until week 24 or month 6 of re-treatment. Improvements in DAS28-ESR and EULAR responses were more pronounced in seropositive patients. RF was a predictor of DAS28-ESR change to study end. Safety analysis showed the established profile of RTX.


RTX was safe and effective in a real-life setting with rapid and sustained improvement in RA signs and symptoms.


Therapie Wirksamkeit Sicherheit Observational study Response latency Safety 

Rituximab im klinischen Alltag bei schwerer aktiver rheumatoider Arthritis

Eine prospektive, nichtinterventionelle Studie in Deutschland


Ziel der Arbeit

Ziel war die Untersuchung von Sicherheit, Wirksamkeit und Wirkeintritt von Rituximab (RTX) bei schwerer aktiver rheumatoider Arthritis (RA) im klinischen Alltag.


Es handelt sich um eine prospektive multizentrische nichtinterventionelle Studie in rheumatologischen Praxen und Ambulanzen in Deutschland. Nicht mit RTX vorbehandelte erwachsene Patienten sollten gemäß Fachinformation und Entscheidung ihres Arztes eine Behandlung mit RTX erhalten, ggf. auch eine Retherapie (Therapiefortsetzung). Primärer Endpunkt war die Änderung des „Disease Activity Score“ nach Beurteilung von 28 Gelenken und der Blutsenkungsgeschwindigkeit (DAS28-BSG) von Therapiebeginn zu Woche 24 sowie ggf. von Beginn zu Monat 6 einer Retherapie.


Eine RTX-Primärtherapie erhielten 1653 Patienten, 99,2 % davon nach krankheitsmodifizierenden Antirheumatika („disease-modifying antirheumatic drugs“, DMARD) und 75,5 % nach Vortherapie mit einem Tumornekrosefaktor(TNF)-α-Inhibitor. Für 820 Patienten wurde nach einem mittleren Intervall von 8,0 Monaten eine Retherapie dokumentiert. Die DAS28-BSG sank von 5,3 vor Therapie auf 3,8 nach 24 Wochen (−1,5; 95%-Konfidenzintervall, 95%-KI: −1,6; −1,4) bzw. von 4,1 vor Beginn einer Retherapie auf 3,5 zu Studienende (Veränderung gegenüber dem Ausgangswert: −1,8; 95%-KI: −2,0; −1,7). Die Verbesserung der DAS28-BSG sowie der Gelenkfunktion (Health Assessment Questionnaire, HAQ) wurde überwiegend in den ersten 12 Wochen der Behandlung mit RTX erzielt; die DAS28-BSG fiel bis Woche 24 bzw. bis Monat 6 unter Retherapie weiter ab. Verbesserungen hinsichtlich DAS28-BSG sowie EULAR-Kriterien (European League Against Rheumatism) waren bei seropositiven Patienten stärker ausgeprägt, die Positivität für den Rheumafaktor (RF) war prädiktiv für die Veränderung der DAS28-BSG unter Retherapie. Die Behandlungssicherheit von RTX entsprach dem bekannten Profil.


Im klinischen Alltag erwies sich RTX als sicher und wirksam mit einer rasch einsetzenden und anhaltenden Besserung der Symptomatik der rheumatoiden Arthritis.


Therapy Effectiveness Safety Beobachtungsstudie Wirklatenz Sicherheit 



The study was sponsored by Roche Pharma AG, Grenzach-Wyhlen, Germany. Medical writing assistance was provided by Physicians World Europe GmbH, supported by Roche Pharma AG.

Compliance with ethical guidelines

Conflict of interest

A. Krause: speakers’ bureau for Abbvie, Berlin-Chemie, BMS, Celgene, Chugai, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi, UCB; consultancy fees from Abbvie, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi; research grants from Abbvie, Ovamed, Roche. P.M. Aries: speakers’ bureau for Abbvie, BMS, Celgene, Chugai, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Mundipharma, consultancy fees from Abbvie, Celgene, Lilly, Medac, Novartis, Pfizer, Roche, Sanofi; Chugai, Roche. C. Fiehn: lecturer fees from Roche. H.-M. Lorenz: consultancy/lecturer fees, support for scientific projects, or travel reimbursements from Abbvie, Actelion, AstraZeneca, Bayer Vital, Baxter, Biogen, BMS, Celgene, Chugai, GSK, Janssen-Cilag, Lilly, Medac, MSD, Novartis, Octapharma, Pfizer, Roche, Shire, SOBI, UCB. L. Meier: consultancy/lecturer fees from Abbvie, BMS, Chugai-Roche, Lilly, Medac, MSD, Pfizer. U. Müller-Ladner: consultancy/lecturer fees from Roche, Chugai. A. Schwarting: honoraria from GSK, research grants from AbbVie, BMS, Pfizer. H.-P. Tony: consultancy/lecturer fees from Abbvie, AstraZeneca, BMS, Chugai, Janssen-Cilag, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi. M.A. Peters is an employee of Roche Pharma AG. J. Wendler: consultancy/lecturer fees from Roche. S. Berger, H. Kellner and G.A. Müller declare that they have no competing interests.

This article does not contain any studies with human participants or animals performed by any of the authors.


  1. 1.
    Chatzidionysiou K, Lie E, Nasonov E et al (2016) Effectiveness of two different doses of rituximab for the treatment of rheumatoid arthritis in an international cohort: data from the CERERRA collaboration. Arthritis Res Ther 18:50CrossRefGoogle Scholar
  2. 2.
    Chatzidionysiou K, Lie E, Nasonov E et al (2011) Highest clinical effectiveness of rituximab in autoantibody-positive patients with rheumatoid arthritis and in those for whom no more than one previous TNF antagonist has failed: pooled data from 10 European registries. Ann Rheum Dis 70:1575–1580CrossRefGoogle Scholar
  3. 3.
    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 71:374–377CrossRefGoogle Scholar
  4. 4.
    Cohen MD, Keystone E (2015) Rituximab for rheumatoid arthritis. Rheumatol Ther 2:99–111CrossRefGoogle Scholar
  5. 5.
    Cohen SB, Emery P, Greenwald MW et al (2006) Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum 54:2793–2806CrossRefGoogle Scholar
  6. 6.
    Couderc M, Mathieu S, Pereira B et al (2013) Predictive factors of rituximab response in rheumatoid arthritis: results from a French university hospital. Arthritis Care Res (Hoboken) 65:648–652CrossRefGoogle Scholar
  7. 7.
    Emery P, Deodhar A, Rigby WF et al (2010) Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naive with active rheumatoid arthritis and an inadequate response to methotrexate. Ann Rheum Dis 69:1629–1635 (Study Evaluating Rituximab’s Efficacy in MTX iNadequate rEsponders (SERENE))CrossRefGoogle Scholar
  8. 8.
    Emery P, Gottenberg JE, Rubbert-Roth A et al (2015) Rituximab versus an alternative TNF inhibitor in patients with rheumatoid arthritis who failed to respond to a single previous TNF inhibitor: SWITCH-RA, a global, observational, comparative effectiveness study. Ann Rheum Dis 74:979–984CrossRefGoogle Scholar
  9. 9.
    Emery P, Mease PJ, Rubbert-Roth A et al (2011) Retreatment with rituximab based on a treatment-to-target approach provides better disease control than treatment as needed in patients with rheumatoid arthritis: a retrospective pooled analysis. Rheumatology (Oxf) 50:2223–2232CrossRefGoogle Scholar
  10. 10.
    Harrold LR, Reed GW, Shewade A et al (2015) Effectiveness of Rituximab for the treatment of rheumatoid arthritis in patients with prior exposure to anti-TNF: results from the CORRONA Registry. J Rheumatol 42:1090–1098CrossRefGoogle Scholar
  11. 11.
    Isaacs JD, Cohen SB, Emery P et al (2013) Effect of baseline rheumatoid factor and anticitrullinated peptide antibody serotype on rituximab clinical response: a meta-analysis. Ann Rheum Dis 72:329–336CrossRefGoogle Scholar
  12. 12.
    Kekow J, Mueller-Ladner U, Schulze-Koops H (2012) Rituximab is more effective than second anti-TNF therapy in rheumatoid arthritis patients and previous TNFalpha blocker failure. Biologics 6:191–199PubMedPubMedCentralGoogle Scholar
  13. 13.
    Quartuccio L, Fabris M, Salvin S et al (2009) Rheumatoid factor positivity rather than anti-CCP positivity, a lower disability and a lower number of anti-TNF agents failed are associated with response to rituximab in rheumatoid arthritis. Rheumatology (Oxf) 48:1557–1559CrossRefGoogle Scholar
  14. 14.
    Richter A, Pattloch D, Manger B et al (2016) Initiation of biologic treatment over the past 15 years reflects changes in treatment strategies: results from the prospective cohort of the German Biologics Register Rabbit. Ann Rheum Dis 75:874–875CrossRefGoogle Scholar
  15. 15.
    Richter A, Strangfeld A, Herzer P et al (2014) Sustainability of rituximab therapy in different treatment strategies: results of a 3-year followup of a German biologics register. Arthritis Care Res (Hoboken) 66:1627–1633CrossRefGoogle Scholar
  16. 16.
    Sellam J, Hendel-Chavez H, Rouanet S et al (2011) B cell activation biomarkers as predictive factors for the response to rituximab in rheumatoid arthritis: a six-month, national, multicenter, open-label study. Arthritis Rheum 63:933–938CrossRefGoogle Scholar
  17. 17.
    Smolen JS, Keystone EC, Emery P et al (2007) Consensus statement on the use of rituximab in patients with rheumatoid arthritis. Ann Rheum Dis 66:143–150CrossRefGoogle Scholar
  18. 18.
    Solau-Gervais E, Prudhomme C, Philippe P et al (2012) Efficacy of rituximab in the treatment of rheumatoid arthritis. Influence of serologic status, coprescription of methotrexate and prior TNF-alpha inhibitors exposure. Joint Bone Spine 79:281–284CrossRefGoogle Scholar
  19. 19.
    Soliman MM, Hyrich KL, Lunt M et al (2012) Effectiveness of rituximab in patients with rheumatoid arthritis: observational study from the British Society for Rheumatology Biologics Register. J Rheumatol 39:240–246CrossRefGoogle Scholar
  20. 20.
    Strangfeld A, Eveslage M, Kekow J (2009) Effectiveness of treatment with rituximab depends on autoantibody status: results from 2 years of experience in the German biologics register RABBIT. Arthritis Rheum 60:1695 (Abstract)Google Scholar
  21. 21.
    Valleala H, Korpela M, Mottonen T et al (2009) Rituximab therapy in patients with rheumatoid arthritis refractory or with contraindication to anti-tumour necrosis factor drugs: real-life experience in Finnish patients. Scand J Rheumatol 38:323–327CrossRefGoogle Scholar
  22. 22.
    Van Vollenhoven RF, Fleischmann RM, Furst DE et al (2015) Longterm safety of Rituximab: final report of the rheumatoid arthritis global clinical trial program over 11 years. J Rheumatol 42:1761–1766CrossRefGoogle Scholar
  23. 23.
    Vander Cruyssen B, Durez P, Westhovens R et al (2010) The Belgian MIRA (MabThera In Rheumatoid Arthritis) Registry: clues for the optimization of rituximab treatment strategies. Arthritis Res Ther 12:R169CrossRefGoogle Scholar
  24. 24.
    Vassilopoulos D, Delicha EM, Settas L et al (2016) Safety profile of repeated rituximab cycles in unselected rheumatoid arthritis patients: a long-term, prospective real-life study. Clin Exp Rheumatol 34:893–900PubMedGoogle Scholar
  25. 25.
    Wendler J, Burmester GR, Sorensen H et al (2014) Rituximab in patients with rheumatoid arthritis in routine practice (GERINIS): six-year results from a prospective, multicentre, non-interventional study in 2,484 patients. Arthritis Res Ther 16:R80CrossRefGoogle Scholar

Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2018

Authors and Affiliations

  • A. Krause
    • 1
    Email author
  • P. M. Aries
    • 2
  • S. Berger
    • 3
  • C. Fiehn
    • 4
  • H. Kellner
    • 5
  • H.-M. Lorenz
    • 6
  • L. Meier
    • 7
  • G. A. Müller
    • 8
  • U. Müller-Ladner
    • 9
  • A. Schwarting
    • 10
  • H.-P. Tony
    • 11
  • M. A. Peters
    • 12
  • J. Wendler
    • 13
  1. 1.Abteilung Rheumatologie und Klinische Immunologie, Klinik für Innere MedizinImmanuel KrankenhausBerlinGermany
  2. 2.Rheumatologie im StruenseehausHamburgGermany
  3. 3.Private PracticeNaunhofGermany
  4. 4.Praxis für Rheumatologie und klinische ImmunologieBaden-BadenGermany
  5. 5.Private Practice and Division of RheumatologyKH NeuwittelsbachMunichGermany
  6. 6.Division of RheumatologyUniversity Hospital HeidelbergHeidelbergGermany
  7. 7.RheumaPraxisHofheimGermany
  8. 8.Department of Nephrology and RheumatologyUniversity Hospital GöttingenGöttingenGermany
  9. 9.Department of Rheumatology and Clinical ImmunologyKerckhoff Hospital GmbHBad NauheimGermany
  10. 10.First Department of Medicine, University HospitalJohannes Gutenberg-UniversityMainzGermany
  11. 11.Division of Clinical Immunology/Rheumatology, Department of Internal Medicine IIUniversity of WürzburgWürzburgGermany
  12. 12.Medical Management RheumatologyRoche Pharma AGGrenzach-WyhlenGermany
  13. 13.Private PracticeErlangenGermany

Personalised recommendations