skip to the content

Development of MabThera®

Pre-1995

A major role for B cells in rheumatoid arthritis (RA) is hypothesised following the discovery of rheumatoid factors. Initial interest wanes during the 1980s and early 1990s as the focus shifts to T cells.1,2

1997

MabThera® is approved in the US as the first B cell-targeted therapy for the treatment of relapsed indolent non-Hodgkin’s lymphoma (NHL).

1999

First indications of the potential for MabThera® in RA: remission of inflammatory arthropathy following MabThera® treatment of NHL.3

2001

Demonstration that T cell activation in the rheumatoid synovium is B cell dependent.4

2001

Preliminary data indicate the efficacy of MabThera® for the treatment of patients with RA.5–7

2004

A Phase IIa trial of MabThera® therapy in RA demonstrates significant and long-lasting treatment responses.8 A full clinical development programme is initiated.

2006

Results from the Phase IIb DANCER trial demonstrate the efficacy of 500 mg and 1000 mg doses of MabThera® at reducing the signs and symptoms of RA.9 The 1000 mg dose is associated with the attainment of high efficacy endpoints.

2006

Results of the multi-centre Phase III REFLEX trial are published, demonstrating significant and clinically meaningful benefits for patients who have had an inadequate response to TNF inhibitors.10

2006

MabThera® is approved in the EU and US for the treatment of patients with active RA and an inadequate response to TNF inhibitors.

2007

Consensus statement on the use of rituximab in patients with RA concludes that MabThera® “constitutes a major advance in the therapeutic armamentarium for patients with rheumatoid arthritis”.11

2007

Demonstration that repeat courses of MabThera® are associated with consistent and sustained efficacy, and no clinically significant safety concerns.12

2008

REFLEX trial data demonstrate significant improvements in patient-reported outcomes with MabThera® therapy.13

2009

Radiographic data from the REFLEX trial provide the first evidence that MabThera® therapy significantly slows the progression of structural joint damage in patients with RA.14

2010

Two year radiographic data from the REFLEX trial provide long term evidence that MabThera® slows progression of structural joint damage.15  Publication of long term safety data in 2578 patients demonstrates that MabThera® remains well tolerated.16
 
  1. Browning JL. Nat Rev Drug Discovery 2006;5:564–576.
  2. Edwards JCW & Cambridge G. Nat Rev Immunol 2006;6:394–403.
  3. Protheroe A, et al. Rheumatology 1999;38:1150–1152.
  4. Takemura S, et al. J Immunol 2001;167:4710–4718.
  5. Edwards JCW & Cambridge G. Rheumatology 2001;40:205–211.
  6. Leandro MJ, et al. Ann Rheum Dis 2002;61:883–888.
  7. De Vita S, et al. Arthritis Rheum 2002;46:2029–2033.
  8. Edwards JCW, et al. N Engl J Med 2004;350:2572–2581.
  9. Emery P, et al. Arthritis Rheum 2006;54:1390–1400.
  10. Cohen S, et al. Arthritis Rheum 2006;54:2793–2806.
  11. Smolen JS, et al. Ann Rheum Dis 2007;66:143–150.
  12. Keystone E, et al. Arthritis Rheum 2007;56:3896–3908.
  13. Keystone E, et al. Arthritis Rheum 2008;59:785–93.
  14. Keystone E, et al. Ann Rheum Dis 2009;68:216–221.
  15. Keystone E, et al. Ann Rheum Dis 2010;69:1158–61.
  16. van Vollenhoven RF, et al. J Rheumatol 2010;37:558–67.