Intervention
Autoantibodies and other markers
Was clinical endpoint met?
Rituximab 500–1000 mg 2 weeks
apart
Rituximab 1000 mg on days 1, 15,
168, 182
Increase of BLyS of 118%
Improvement of BILAG score in patients
with SLE
No statistically significant change in
lupus nephritis activity
SLE
Cambridge et al.1
Furie et al.2
Lu et al.3
Merrill et al.4
Rituximab 1000 mg,
750 mg of cyclophosphamide,
100–250 mg of
methylprednisolone 2 weeks apart
Rituximab 1000 mg on days 1,15,
168, 182
Tew et al..5
Rituximab 1000 mg on day 1, 15,
168, 182
Wallace et al.6
Belimumab (1,4,10 mg) given at
days 0,14, and 28. Then q28 days.
RA
Cambridge et al.7
Cohen et al.8
Emery et al.9
Thurlings et al.10
ANCA vasculitis
Stone et al.11
Rituximab in range doses
Rituximab 1000 mg on days 1 and
15
Ritixumab 500 or 1000 mg on days
1 and 15
Rituximab 1000 mg on days 1 and
15
Rituximab 375 mg/m2 qweekly for
4 weeks
Statistically significant decrease of
dsDNA
Statistically significant increase of C3
*Similar levels of decrease in dsDNA and
C3 in responders and nonresponders
Decrease of dsDNA 60%
Increase of C3 16%
Improvement of BILAG score in patients
with SLE
Decrease of dsDNA 76% in patients with
detectable anti-dsDNA at baseline
Increase of C3 of 129% in patients who
began with a low complement level
Increase of C4 of 173% in patients who
began with a low complement level
No significant changes in Anti RNP, antiSm, anti-Ro, or anti-LA.
Statistically significant decrease in
dsDNA
Statistically significant decrease in IgM
and IgG anti-cardiolipin
Decrease of dsDNA at 29%
Increase of C3 at 22%
No significant benefit in SLE activity
Significant decrease of IgA-RF, IgG-RF,
and ACPA levels in patient responders to
rituximab
Decrease of RF of 55% in patients who
are RF positive at baseline
Decrease in IgM RF ranging from 11.5%
to 47.9% in patient s treated with
rituximab with baseline positive RF
Statistically significant decrease of IgMRF
Statistically significant decrease of ACPA
Significant clinical improvement in
patients with RA
47% of the treatment group who were
ANCA positive became negative at 6
months
Rituximab was shown to be noninferior
to cyclophosphomide in treatment of
ANCA vasculitis
No significant clinical benefit in SLE
disease activity
Reduction of SLE disease activity was not
significant
Significant clinical improvement in
patients with RA
Significant clinical improvement in
patients with RA
N/A
Abbreviations: ACPA, anti-citrillunated protein antibody; ANCA, anti-neutrophil cytoplasmic antibodies; anti-RNP,
anti-ribonucleic protein; anti-Sm, anti Smith; BILAG; British Isles Assessment Group; BLyS, B Lymphocyte
Stimulator; C3, complement 3; C4, complement 4; dsDNA, double stranded DNA; RA, rheumatoid arthritis; RF,
rheumatoid factor; SLAM, Systemic Lupus Activity Measure; SLE, systemic lupus erythematosus.
References
1.
2.
3.
4.
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7.
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9.
10.
11.
Cambridge, G., et al. B cell depletion therapy in systemic lupus erythematosus:
relationships among serum B lymphocyte stimulator levels, autoantibody profile and
clinical response. Ann Rheum Dis 67, 1011-1016 (2008).
Furie, R., Rovin, B., Appel, G., Kamen, D.L., Fervenza, F.C., Spindler, A., et al. Effect of
Rituximab (RTX) On Anti-dsDNA and C3 Levels and Relationship to Response: Results
From the LUNAR Trial [abstract]. Arthritis Rheum 60, 271 (2009).
Lu, T.Y., et al. A retrospective seven-year analysis of the use of B cell depletion therapy
in systemic lupus erythematosus at University College London Hospital: the first fifty
patients. Arthritis Rheum 61, 482-487 (2009).
Merrill, J.T., et al. Efficacy and safety of rituximab in moderately-to-severely active
systemic lupus erythematosus: the randomized, double-blind, phase II/III systemic lupus
erythematosus evaluation of rituximab trial. Arthritis Rheum 62, 222-233.
Tew, G.W., et al. Baseline autoantibody profiles predict normalization of complement
and anti-dsDNA autoantibody levels following rituximab treatment in systemic lupus
erythematosus. Lupus 19, 146-157.
Wallace, D.J., et al. A phase II, randomized, double-blind, placebo-controlled, doseranging study of belimumab in patients with active systemic lupus erythematosus.
Arthritis Rheum 61, 1168-1178 (2009).
Cambridge, G., et al. Serologic changes following B lymphocyte depletion therapy for
rheumatoid arthritis. Arthritis Rheum 48, 2146-2154 (2003).
Cohen, S.B., et al. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis
factor therapy: Results of a multicenter, randomized, double-blind, placebo-controlled,
phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis
Rheum 54, 2793-2806 (2006).
Emery, P., et al. The efficacy and safety of rituximab in patients with active rheumatoid
arthritis despite methotrexate treatment: results of a phase IIB randomized, double-blind,
placebo-controlled, dose-ranging trial. Arthritis Rheum 54, 1390-1400 (2006).
Thurlings, R.M., et al. Synovial tissue response to rituximab: mechanism of action and
identification of biomarkers of response. Ann Rheum Dis 67, 917-925 (2008).
Stone, J.H., et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis.
N Engl J Med 363, 221-232 (2010).