Rheumatoid arthritis and B cells
Thirty years ago, B cells were considered a significant contributing factor in the pathophysiology of rheumatoid arthritis (RA) because of the association of the disease with polyclonal B cell activation and the presence of autoantibodies, such as rheumatoid factor (RF), and immune complexes in the joint ( Hirano 2002 ; Zvaifler 1973 ). However, for much of the past 20 years, RA has mainly been considered a T cell-mediated disease ( Hirano 2002 ). Only recently has new evidence rekindled strong interest in B cells and their important role in the pathogenesis of RA ( Silverman et al. 2003 ).
This rekindled interest is due to MabThera®, the first and only selective B cell therapy for RA ( Silverman et al. 2003 ; Shaw et al. 2003 ). MabThera treatment inhibits the progression of joint damage that is typical of the disease process in RA ( Keystone et al. 2006 ). It also provides lasting improvements in the signs and symptoms of the disease, such as swelling, pain, stiffness and fatigue ( Cohen et al. 2006 ). Furthermore, patients receiving MabThera have experienced clinically meaningful improvements in their disability and health-related quality of life (HRQOL), as measured by significant improvements in patient-reported outcomes on the Health Assessment Questionnaire Disability Index (HAQ-DI) and Mean Medical Outcomes Study Short-Form (36-item) Health Survey (SF-36). Repeat courses of MabThera, 6–12 months after the initial course of just two infusions, provide continued improvement of symptoms. Response to MabThera is maintained or further improved with repeated treatment courses ( Keystone et al. 2006 ; Tak et al. 2006 ).
Not only is MabThera an effective RA treatment but it also has a positive safety profile. MabThera selectively targets a subset of B cells that express CD20, leaving stem, pro-B and plasma cells unaffected. As a result, B cell populations recover after MabThera treatment and acquired immunity is left intact ( Edwards et al. 2004 ; Shaw et al. 2003 ; Silverman et al. 2003 ; Sell & Max 2001 ; Roitt et al. 2001 ; Cohen et al. 2006 ). Infusion reactions, which are the most common adverse event observed with MabThera, are mainly mild-to-moderate, easily managed and reduced with further infusions ( van Vollenhoven et al. 2005 ; van Vollenhoven et al. 2005 ; Cohen et al. 2006 ). In addition, the infection rate observed in patients treated with MabThera lies within the normal range for RA patients ( Moreland et al. 2006 ) and the safety profile of MabThera remains unchanged with repeated treatment courses. As well as being used in the treatment of RA, MabThera has been used to treat more than 730,000 oncology patients over a 7-year period without major safety concerns ( Cohen et al. 2006 ).
MabThera is administered on Day 1 and 15, with a dosing interval of 6–12 months according to disease activity ( Cohen et al. 2006 ). This unique dosing regimen allows clinic visits to be less frequent than with other RA infusion treatments. Overall, the average annual treatment costs of MabThera are lower than those of any other biologic disease-modifying anti-rheumatic drug (DMARD) ( Brown et al. 2006 ; Lewis et al. 2006 ; Alvarez et al. 2006 ; Schach et al. 2006 ). Therefore, MabThera offers an innovative, effective and lasting treatment for patients with RA.