Rituxan Clinical Data
3 critical roles B cells may play in RA
B cells are believed to contribute to the immune processes that lead to inflammation and joint damage in RA
Contributes to T-cell cytokine production and activation of other immune cells in the inflammatory cascade.1,2
In circumstances observed in vitro, B cells were able to present antigen up to 10,000-fold more efficiently than other antigen-presenting cells.3
Immune complexes composed of autoantibodies, including anti-CCP and RF, help perpetuate the inflammatory cascade.4-7
B cells are implicated in the production of proinflammatory cytokines such as IL-6, IL-1, and TNF.3,7,8
In some models, IL-6, IL-1, and TNF—as well as other factors—enhance RANKL, which mediates osteoclastogenesis.9-11
IMPORTANT SAFETY INFORMATIONCONCOMITANT USE WITH BIOLOGIC AGENTS AND DMARDS OTHER THAN METHOTREXATE IN RA:
- Limited data are available on the safety of the use of biologic agents or DMARDs other than methotrexate in patients exhibiting peripheral B-cell depletion following treatment with rituximab
- Observe patients closely for signs of infection if biologic agents and/or DMARDs are used concomitantly
Mechanism of action of Rituxan
CD20 is not found on stem cells, Pro-B cells, normal plasma cells, or other normal tissues.1
Because they lack CD20, stem cells and plasma cells are not selectively targeted by Rituxan.2
How Rituxan Works: MOA
Understanding how Rituxan works in Rheumatoid Arthritis.
- O'Neill SK, Shlomchik MJ, Glant TT, Cao Y, Doodes PD, Finnegan A. Antigen-specific B cells are required as APCs and autoantibody-producing cells for induction of severe autoimmune arthritis. J Immunol. 2005;174(6):3781-3788.
- Takemura S, Klimiuk PA, Braun A, Goronzy JJ, Weyland CM. T cell activation in rheumatoid synovium is B cell dependent. J Immunol. 2001;167(8):4710-4718.
- Lund FE, Garvy BA, Randall TD, Harris DP. Regulatory roles for cytokine-producing B cells in infection and autoimmune disease. Curr Dir Autoimmun. 2005;8:25-54.
- Roosnek E, Lanzavecchia A. Efficient and selective presentation of antigen-antibody complexes by rheumatoid factor B cells. J Exp Med. 1991;173(2):487-489.
- Abrahams VM, Cambridge G, Lydyard PM, Edwards JCW. Induction of tumor necrosis factor production by adhered human monocytes: a key role for FcY receptor type IIIA in rheumatoid arthritis. Arthritis Rheum. 2000;43(3):608-616.
- Sutton B, Corper A, Bonagura V, Taussig M. The structure and origin of rheumatoid factors. Immunol Today. 2000;21(4):177-183.
- Silverman GJ, Carson DA. Roles of B cells in rheumatoid arthritis. Arthritis Res Ther. 2003;5(suppl 4):S1-S6. doi:10.1186/ar1010.
- McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol. 2007;7(6):429-442.
- Duddy ME, Alter A, Bar-Or A. Distinct profiles of human B cell effector cytokines: A role in immune regulation? J Immunol. 2004;172(6):3422-3427.
- Lam J, Takeshita S, Barker JE, Osami K, Ross FP, Teitelbaum SL. TNF-α induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand. J Clin Invest. 2000;106(12):1481-1488.
- Wei S, Kitaura H, Zhou P, Ross FP, Teitelbaum SL. IL-1 mediates TNF-induced osteoclastogenesis. J Clin Invest. 2005;115(2):282-290. doi:10.1172/JCI200523394.
- Palmqvist P, Persson E, Conaway HH, Lerner UH. IL-6, leukemia inhibitory factor, and oncostatin M stimulate bone resorption and regulate the expression of receptor activator of NF-B ligand, osteoprotegerin, and receptor activator of NF-B in mouse calvariae. J Immunol. 2002;169(6):3353-3362.
- Rituxan [package insert]. South San Francisco, CA: Biogen Idec Inc., and Genentech USA, Inc.; February 2012.
- Cohen SB, Emery P, Greenwald MW, et al; for the REFLEX Trial Group. 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. 2006;54 (9):2793-2806. doi:10.1002/art.22025.