Best Practice & Research Clinical Rheumatology
Volume 24, Issue 4 , Pages 553-563 , August 2010

Targeting the B Cell in Rheumatoid Arthritis

  • Stanley B. Cohen, MD (Co-Medical Director, Clinical Professor of Internal Medicine)

      Affiliations

    • Metroplex Clinical Research Center, 8144 Walnut Hill Lane, Suite 800, Dallas TX 75231, USA
    • UT Southwestern Medical School, Dallas, TX, USA
    • Corresponding Author InformationTel.: +1 214 540 0646; Fax: +1 214 540 0617.

References 

  1. Edwards JC, Cambridge G. Sustained Improvement in Rheumatoid Arthritis following a Protocol to Designed to Deplete B Lymphocytes. Rheumatology. 2001;40:205–211
  2. Hamel K, Doodes P, Cao Y, et al. Suppression of Proteoglycan-Induced Arthritis by Anti-CD20 B cell Depletion therapy is Mediated by Reduction in Autoantibodies and CD4 + Reactivity. J of Immunology. 2008;180:4994–5003
  3. Eisenberg RA, et al. The Role of B cell Abnormalities in the Systemic Autoimmune Syndromes of lpr and gld Mice. Semin Immunol. 1994;6:49–54
  4. Takemura S, Klimiuk PA, Braun A, et al. T cell activation in rheumatoid arthritis is B cell dependent. J Immunol. 2001;167:4710–4718
  5. Edwards JCW, Cambridge G, Abrahams VM. Do self-perpetuating B lymphocytes drive human autoimmune disease?. Immunology. 1999;97:188–196
  6. Silverman GJ. Therapeutic B Cell Depletion and Regeneration in Rheumatoid Arthritis. Arth and Rheum. 2006;54:2356–2367
  7. Cambridge G, Leandro MJ, Edwards JCW, et al. Serologic Changes Following B Lymphocyte depletion therapy for rheumatoid arthritis. Arth and Rheum. 2003;48:2146–2154
  8. Rosnek E, LanzavecchiaEfficient A, Presentation Selective. of Antigen-antibody Complexes by rheumatoid Factor B cells. J Exp Med. 1991;173:487–489
  9. Fu YX, Huang G, Wang Y, et al. B Lymphocytes induce the formation of follicular dendritic cell clusters in a lymphotoxin alpha-dependent fashion. J Exp Med. 1998;187:1009–1018
  10. Einfield DA, Brown JP, Valentine MA, et al. Molecular Cloning of the Human B cell CD20 Receptor Predicts a Hydrophobic Protein with Multiple Transmembrane Domains. EMBO J. 1988;7:711–717
  11. Chynes RA, Towers TL, Presta LG, et al. Inhibitory Fc receptors modulate in vivo cytotoxicity against tumor targets. Nat Med. 2000;6:443–446
  12. Cartron G, Dacheux L, Salles G, et al. Therapeutic Activity of humanized anti-CD20 Monoclonal Antibody and polymorphism in IgG Fc Receptor FcGamma R111a Gene. Blood. 2002;99:754–758
  13. Emery P, Fleischmann RM, Filipwicz-Sosnowski A, et al. The Efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment: results of a Phase IIB Randomized Trial. Arth and Rheum. 2006;54:1390–1400
  14. Breedveld F, Agarwal S, Yin M, et al. Rituximab Pharmacokinetics in Patients with rheumatoid Arthritis: B cell Levels do not Correlate with Clinical Response. J Clin Pharmacol. 2007;47:1119–1131
  15. Looney RJ, Anolik JH, Campbell D, et al. B cell depletion as a novel treatment for systemic lupus erythematosus: a Phase I/II dose-escalation trial of Rituximab. Arthritis Rheum. 2004;50:2580–2589
  16. Dass S, Rawstron A, Vital E, et al. Highly sensitive B cell analysis predicts response to rituximab therapy in rheumatoid arthritis. Arthritis Rheum. 2008;58:2993–2999
  17. Onno Teng YK, Levarht Nivine EW, Hashemi M, et al. Immunohistochemical analysis as a means to predict responsiveness to rituximab treatment. Arthritis Rheum. 2007;56:3909–3918
  18. Leaandro MJ, Cambridge G, Ehrenstein MR, et al. Reconstitution of peripheral blood b cells after depletion with rituximab in patients with rheumatoid arthritis. Arthritis Rheum. 2006;54:613–620
  19. Thurlings RM, Vos K, Wijbrandts CA. Synovial tissue response to rituximab:mechanism of action and identification of biomarkers of response. Ann Rheum Dis. 2008;67:917–925
  20. Roll P, Dorner T, Tony HP. Anti-CD20 Therapy in patients with rheumatoid arthritis. Arthritis Rheum. 2008;58:1566–1575
  21. Edwards JC, Szczepanski L, Szechinski J, et al. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med. 2004;350:2572–2581
  22. Cohen S, Keystone E, Genovese M, et al. Continued inhibition of structural damage in rheumatoid arthritis patients treated with rituximab at 2 years: REFLEX study. Arthritis Rheum. 2006;54:1390–1400
  23. Tak P.P, Cohen S, Emery P et al. Clinical Repsonse Following The First Treatment Course with Rituximab: Effect of Baseline Autoantibody Status. EULAR meeting 2008. FRI0192.
  24. Silverman G, Schwartzman S, Townsend M et al. Identification of Biomarkers for enhanced Benefit to Rituximab in Rheumatoid Arthritis: Role of Autoantibodies and Inflammatory Markers. Abstract ACR meeting 2009
  25. Keystone E, Emery P, Peterfy CG, et al. Rituximab inhibits structural joint damage in patients with rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitor therapies. Ann Rheum Dis. 2009;68:216–221
  26. Emery P, Rigby WF, Combe B, et al. Efficacy and safety of rituximab as first-line biologic therapy in patients with active rheumatoid arthritis: results of a phase III randomized controlled study (SERENE). ACR Abstract 08-A-1290-ACR meeting 2008.
  27. Rubbert-Roth A, Tak PP, Bombardieri S, et al. Efficacy and safety of various dosing regimens of rituximab in patients with active RA; results of a phase III randomized study (MIRROR). ACR Abstract 08-A-1024-ACR meeting 2008.
  28. Mease PJ, Cohen S, Gaylis NB, et al. Efficacy, safety, and dose frequency of retreatment with rituximab in RA: results from a randomized controlled trial (SUNRISE). ACR Abstract 08-A-3705-ACR meeting 2008.
  29. Tak PP, Rigby W, Rubbert A et al. Inhibition Of Joint Damage and Improved Clinical Outcomes With a Combination Of Rituximab And Methotrexate In Patients With Early Active Rheumatoid Arthritis Who Are Naïve To Mtx: A Randomized Active Comparator Placebo Controlled Trial. EULAR meeting 2009:Abstract OP-0022
  30. Bingham C, Looney R, Deodhar A, et al. Results from a controlled clinical trial (SIERRA) to evaluate primary and recall responses to immunizations in RA patients treated with rituximab. ACR Abstract 08-A-3626-ACR Meeting 2008.
  31. Genovese M, Breedveld F, Emery P et al. Rate of Serious Infections in Rituximab Treated Patients with Rheumatoid Arthritis Who subsequently Received Other Biologic Therapies. Abstract 0097 EULAR 2009.
  32. Keystone E, Fleischmann R, Emery P, et al. Safety and efficacy of additional courses of rituximab in patients with active rheumatoid arthritis: An open-label extension analysis. Arthritis Rheum. 2007;56:3896–3908
  33. van Vollenhaven RF, Emery P, Bingham C.O. Long-Term Safety of Rituximab: Follow-up of the RA Clinical Trials and Re-Treatment Population. EULAR meeting 2009 meeting.OP-0026.
  34. Genentech and Biogen . Important Drug Warning New Safety Information. Avaliable at: http://www.fda.gov/medwatch/safety/2008/rituxan_DHCP_Final%2094411700.pdf2008;Accessed March 2, 2009
  35. Carson K, Evans A, Richey E, et al. Progressive Multifocal Leukoencephalopathy after Rituximab Therapy in HIV-negative Patients: a Report of 57 Cases from the Research on Adverse Drug Events and Reports Project. Blood. 2009;113:4834–4840
  36. Genovese M, Kaine J, Lowenstein M, et al. Ocrelizumab, a humanized anti-CD20 monoclonal antibody, in the treatment of patients with rheumatoid arthritis: A phase I/II randomized, blinded, placebo-controlled, dose-ranging study. Arthritis Rheum. 2008;58:2652–2661
  37. Burge D;Chopiak V,Dvoretskiy L, et al. TRU-015 Improves Rheumatoid Arthritis Disease Activity in a Randomized, Double-Blind, Placebo-Controlled, Multi-Center Phase 2 Dose Ranging Trial. Abstract. ACR meeting 2007.
  38. Stromatt S, Chopiak V, Dvoretskiy L et al. Sustained Safety and Efficacy of TRU-015 with Continued Retreatment of Rheumatoid Arthritis Subjects Following a Phase 2B Study. Abstract ACR meeting 2009.
  39. Østergaard M, Baslund B, Rigby W et al. Ofatumumab (HUMAX-CD20), A Fully HumanCD20 MONOCLONAL Antibody, In the Treatment of Rheumatoid Arthritis. Early results from an Ongoing, Double Blind, Randomized, Placebo Controlled Clinical Trial. EULAR meeting 2007:OP0232
  40. Schiemann B, Gommerman Jl, Vora K, et al. An essential role of BAFF in the normal development of b cells through a BCMA –Independent Pathway. Science. 2002;293:2111–2114
  41. Khare SD, Sarosi I, Xia Xz. Severe B cell Hyperplasia and Autoimmune disease in TALL-1 Transgenic Mice. Proc Natl Acad Sci USA. 2000;(7):3370–3375
  42. Carbonatto M, Yu P, Bertolino M, et al. nonclinical safety, pharmacokinetics, and pharmacodynamics of atacicept. Immunity. 2001;105:200–210
  43. Cheema GS, Roschke V, Baker KP, et al. Elevated Serum B lymphocyte stimulator levels in patients with systemic immune-based rheumatic diseases. Arth and Rheum. 2001;44:1313–1319
  44. Lavie F, Micell-Richard C, Ittah M. Increase of B Cell Activating Factor of the TNF Fasmily(BAFF) after Rituximab Treatment: insights into a new regulating system of BAFF production. Ann Rheum Dis. 2007;66:700–702
  45. McKay J, Chwalinska-Sadowska H, Boling E, et al. Belimumab, a fully human monoclonal antibody to B-lymphocyte stimulator, combined with standard of care therapy reduces the signs and symptoms of rheumatoid arthritis in a heterogeneous population. Arth and Rheum. 2005;S710;abstract 1920
  46. Genovese M, Filipowicz-Sosnowska A, Merrill J, et al. Differential Responsiveness to Belimumab in combination with Standard of Care therapy in RF+, TNF inhibitor and methotrexate partial responder subgroups with moderate-severe rheumatoid arthritis. abstract Arth and Rheum. 1989;S738
  47. Navarra S, Guzman2 R, Gallacher A. Belimumab, a BLyS-specific inhibitor, reduced disease activity, flares and prednisone use in patients with active sle: efficacy and safety results from the phase 3 BLISS-52 Study. Arth and Rheumatism. 2009;60(10):Supplement(PP.S1-S830)
  48. Tak PP, Thurlings RM, Rossier C, et al. Atacicept in patients with rheumatoid arthritis: Results of a multicenter, phase 1b, double-blind, placebo-controlled, dose-escalating, single- and repeated-dose study. Arth & Rheumatism. January 2008;58(Issue 1):61–72

PII: S1521-6942(09)00142-9

doi: 10.1016/j.berh.2009.11.006

Best Practice & Research Clinical Rheumatology
Volume 24, Issue 4 , Pages 553-563 , August 2010