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).
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.
Rubbert-Roth
Andrea
A
Department of Internal Medicine, University of Cologne, Cologne, Germany. andrea.rubbert@medizin.uni-koeln.de
Tak
Paul P
PP
Zerbini
Cristiano
C
Tremblay
Jean-Luc
JL
Carreño
Luis
L
Armstrong
Gillian
G
Collinson
Neil
N
Shaw
Tim M
TM
D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage* / Q000009:adverse effects; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D016896:Treatment Outcome
D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D000069283:Rituximab
Ann Rheum Dis. 2007 Feb;66(2):143-50
17068064
Arthritis Rheum. 1995 Jun;38(6):727-35
7779114
J Rheumatol. 2005 May;32(5):811-9
15868614
Arthritis Rheum. 2008 Dec;58(12):3657-64
19035505
Arthritis Rheum. 1996 Jan;39(1):34-40
8546736
Rheumatology (Oxford). 2011 Dec;50(12):2223-32
21926153
Arthritis Rheum. 2007 Dec;56(12):3896-908
18050221
N Engl J Med. 2004 Jun 17;350(25):2572-81
15201414
Arthritis Rheum. 1995 Jan;38(1):44-8
7818570
Pharmacoeconomics. 2004;22(2 Suppl 1):27-38
15157002
Arthritis Rheum. 2008 Oct;58(10):2993-9
18821683
J Rheumatol. 1993 Mar;20(3):557-60
8478873
Arthritis Rheum. 2003 Jan;48(1):35-45
12528101
Arthritis Rheum. 2005 Aug;52(8):2263-71
16052582
Arthritis Rheum. 2006 Sep;54(9):2793-806
16947627
Arthritis Rheum. 2006 May;54(5):1390-400
16649186
Lancet. 1999 Dec 4;354(9194):1932-9
10622295
Med Care. 2003 May;41(5):582-92
12719681
Ann Rheum Dis. 2008 Oct;67(10):1444-7
18535115
J Clin Pharmacol. 2007 Sep;47(9):1119-28
17766699