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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
Originalien

Abstract

Objective

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

Methods

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.

Results

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.

Conclusion

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

Keywords

Therapie Wirksamkeit Sicherheit Observational study Response latency Safety 

Rituximab im klinischen Alltag bei schwerer aktiver rheumatoider Arthritis

Eine prospektive, nichtinterventionelle Studie in Deutschland

Zusammenfassung

Ziel der Arbeit

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

Methoden

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.

Ergebnisse

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.

Schlussfolgerung

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

Schlüsselwörter

Therapy Effectiveness Safety Beobachtungsstudie Wirklatenz Sicherheit 

Notes

Acknowledgements

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.

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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

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