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Clinical Trial
. 2010 Sep;49(9):1683-93.
doi: 10.1093/rheumatology/keq116. Epub 2010 May 12.

Efficacy and safety of various repeat treatment dosing regimens of rituximab in patients with active rheumatoid arthritis: results of a Phase III randomized study (MIRROR)

Andrea Rubbert-Roth  1 , Paul P Tak, Cristiano Zerbini, Jean-Luc Tremblay, Luis Carreño, Gillian Armstrong, Neil Collinson, Tim M Shaw; MIRROR Trial Investigators
Collaborators, Affiliations
Clinical Trial

Efficacy and safety of various repeat treatment dosing regimens of rituximab in patients with active rheumatoid arthritis: results of a Phase III randomized study (MIRROR)

Andrea Rubbert-Roth et al. Rheumatology (Oxford). 2010 Sep.

Abstract

Objective: To evaluate the efficacy and safety of three dosing and repeat treatment regimens of rituximab (RTX) plus MTX in patients with active RA.

Methods: Patients with active RA despite stable MTX (10-25 mg/week) were randomly assigned to one of the three treatment regimens comprising two courses of RTX given 24 weeks apart: 2 x 500 and 2 x 500 mg; 2 x 500 and 2 x 1000 mg (dose escalation); and 2 x 1000 and 2 x 1000 mg. The primary endpoint was proportion of patients achieving ACR20 at Week 48.

Results: At Week 48, ACR20 responses were not statistically significantly different between the dose regimens. Compared with RTX 2 x 500 mg (n = 134) or dose escalation (n = 119), ACR and European League Against Rheumatism (EULAR) outcomes in the RTX 2 x 1000 mg group (n = 93) were consistently higher, with significantly more patients achieving EULAR responses (P = 0.0495). At Week 48, rituximab 2 x 1000 mg was associated with a higher proportion of patients who, following retreatment, maintained or improved their Week 24 responses. Dose escalation from 2 x 500 to 2 x 1000 mg did not appear to be associated with improved outcomes compared with continual 2 x 500 mg. All RTX regimens demonstrated comparable safety.

Conclusions: RTX 2 x 500 and 2 x 1000 mg could not be clearly differentiated, although some efficacy outcomes suggest improved outcomes in the rituximab 2 x 1000 mg group. Retreatment from Week 24 resulted in a sustained suppression of disease activity through to Week 48.

Trial registration: ClinicalTrials.gov NCT00422383.

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Figures

F<sc>ig</sc>. 1
Fig. 1
Overview of study design.
F<sc>ig</sc>. 2
Fig. 2
Disposition of patients up to Week 48. aFourteen patients were randomly assigned to rituximab (RTX) 2 × 1000 mg, placebo. bSome patients received a treatment regimen other than that to which they were randomly assigned. cSix patients received placebo and 25 patients received RTX 2 × 500 mg for their second course (data on these 31 patients treated with non-protocol-specified regimens not shown). dOne patient did not receive a second course of treatment, but completed 25 weeks of follow-up.
F<sc>ig.</sc> 3
Fig. 3
Number of patients achieving an improvement in ACR criteria at Week 48 (mITT population). *P = 0.8156. **P = 0.2419 for RTX (2 × 500 and 2 × 500 mg) vs RTX (2 × 500 mg, 2 × 1000 mg) and RTX (2 × 1000 and 2 × 1000 mg), respectively.
F<sc>ig.</sc> 4
Fig. 4
Summary of clinical efficacy at Week 48. aDAS-28-ESR <2.6. *P = 0.0495 for RTX (2 × 500 and 2 × 500 mg) vs RTX (2 × 500 and 2 × 1000 mg). LDA: low disease activity.
F<sc>ig.</sc> 5
Fig. 5
Plot of mean change from baseline in DAS-28-ESR score by visit, last observation carried forward (LOCF) imputation (mITT population).
See this image and copyright information in PMC

Comment in

References

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