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)

Publication

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)

Journal Paper/Review - Apr 16, 2019

Dörner Thomas, Peters Marvin A, Schwenke Holger, Rubbert-Roth Andrea, Krüger Klaus, Kurthen Reiner, Kellner Herbert, Kästner Peter, Engel Andreas, Schmalzing Marc, Iking-Konert Christof, Burmester Gerd-Rüdiger, Schulze-Koops Hendrik, Tony Hans-Peter

Units

Rheumatologie

PubMed

31025930

Citation

Dörner T, Peters M, Schwenke H, Rubbert-Roth A, Krüger K, Kurthen R, Kellner H, Kästner P, Engel A, Schmalzing M, Iking-Konert C, Burmester G, Schulze-Koops H, Tony H. 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). Clin Exp Rheumatol 2019; 37:937-945.

Type

Journal Paper/Review (English)

Journal

Clin Exp Rheumatol 2019; 37

Publication Date

Apr 16, 2019

Issn Print

0392-856X

Pages

937-945

Brief description/objective

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.