Logo

Early and late responses in patients with rheumatoid arthritis who were conventional synthetic disease-modifying anti-rheumatic drug inadequate responders and were treated with tocilizumab or switched to rituximab: an open-label phase 3 trial (MIRAI)

1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14

  1. Department of Medicine, Rheumatology and Clinical Immunology, Charité Campus Mitte, Medizinische Klinik und Poliklinik m.S. Rheumatologie und Klinische Immunologie, Charité Universitätsmedizin Berlin, Germany. thomas.doerner@charite.de
  2. Division of Rheumatology and Clinical Immunology, Department of Internal Medicine IV, Klinikum der Universität München, Campus Innenstadt, Munich, Germany.
  3. Department of Medicine, Rheumatology and Clinical Immunology, Charité Campus Mitte, Medizinische Klinik und Poliklinik m.S. Rheumatologie und Klinische Immunologie, Charité Universitätsmedizin Berlin, Germany.
  4. Klinik für Nephrologie und Rheumatologie, Med. Klinik III, University Hamburg-Eppendorf, Klinik für Nephrologie und Rheumatologie, Hamburg, Germany.
  5. Rheumatologie/klinische Immunologie, Medizinische Klinik und Poliklinik II, Klinikum der Universität Würzburg, Germany.
  6. Department of Neurophysiology and Pathophysiology, Rheumatologische Schwerpunktpraxis am Feuersee, Stuttgart, Germany.
  7. Private Practice, Ambulantes Rheumazentrum Erfurt, Germany.
  8. Private Practice and Division of Rheumatology, Schwerpunktpraxis für Rheumatologie und Gastroenterologie und Ärztlicher Leiter Abteilung Rheumatologie KH Neuwittelsbach, Munich, Germany.
  9. Private Practice, Aachen, Germany.
  10. Private Practice, Munich, Germany.
  11. Department of Internal Medicine, Klinikum der Universität zu Köln, Klinik für Innere Medizin I, Cologne, Germany.
  12. Rheumatologisches MVZ Dresden GmbH, Dresden, Germany.
  13. Medical Affairs, Roche Pharma AG, Grenzach, Germany.
  14. Rheumatologie/klinische Immunologie, Medizinische Klinik und Poliklinik II, Klinikum der Universität Würzburg, Germany.

CER11687 Submission on line
Full Papers

Free to view (click on article PDF icon to read the article)

Rheumatology Article
Rheumatology Article

 

Abstract

OBJECTIVES:
To evaluate early and late responses in biological-naïve patients with rheumatoid arthritis (RA) initiating tocilizumab and early tocilizumab non-responders who switched to rituximab.
METHODS:
In this open-label, non-randomised phase 3 study, RA patients with inadequate response to conventional synthetic DMARDs received tocilizumab 8 mg/kg intravenously at study begin and weeks 4, 8 and 12. After evaluation at week 16, early responders (Disease Activity Score based on 28 joints-erythrocyte sedimentation rate [DAS28-ESR] <2.6) completed the study; partial responders (DAS28-ESR decrease >1.2 or DAS28-ESR ≥2.6–≤3.2) were to continue tocilizumab through week 28; non-responders (DAS28-ESR decrease ≤1.2) switched to rituximab (1000 mg, weeks 16 and 18) with safety follow-up through week 66.
RESULTS:
Of 519 patients, 222 (42.8%) achieved early DAS28-ESR remission at week 16; 240 patients continued treatment, 213 (41.0%) received tocilizumab, and 27 (5.2%) switched to rituximab. At week 32 DAS28-ESR remission was achieved by 117/213 patients (54.9%) who continued tocilizumab and 4/27 patients (14.8%) who switched to rituximab; good EULAR response was achieved by 66.7% and 25.9% and CDAI remission by 19.2% and 14.8% of patients, respectively. Serious adverse events occurred through week 32 in 45/490 patients (9.2%) who received tocilizumab (serious infections, 2.7%) and through week 66 in 8/27 patients (29.6%) who switched to rituximab.
CONCLUSIONS:
Early response to tocilizumab was observed in 42.8% of patients. Half of early partial responders benefitted from continuing tocilizumab. Switching non-responders to rituximab seems feasible. No new safety signals were observed in patients treated with tocilizumab or switched to rituximab.

PMID: 31025930 [PubMed]

Received: 27/08/2018 - Accepted : 21/01/2019 - In Press: 16/04/2019