B cell targeted therapies

Abstract

Although the precise pathogenesis of rheumatoid arthritis (RA) remains unclear, many cell populations, including monocytes, macrophages, endothelial cells, fibroblasts and B cells, participate in the inflammatory process. Ongoing research continues to evaluate the critical roles played by B cells in sustaining the chronic inflammatory process of RA. These findings have contributed to the development of targeted therapies that deplete B cells, such as rituximab, as well as inhibitors of B lymphocyte stimulation, such as belimumab. In a phase I trial, belimumab treatment significantly reduced CD20+ levels in patients with systemic lupus erythematosus. Phase I and phase II trials of rituximab found that rituximab plus methotrexate achieved significantly better American College of Rheumatology 50% responses for patients with RA than those patients receiving monotherapy with methotrexate. These clinical trial data present promising evidence for B cell targeted therapies as future therapeutic options for RA.

Figure 1

Rituximab in rheumatoid arthritis. Phase IIa: American College of Rheumatology (ACR) responses at 48 weeks (NRI). *P < 0.0001; ^†P = 0.003; ^‡P = 0.03; ^§P = 0.01; P values using Fisher's exact test, comparing MTX with each RTX group. CTX, cyclophosphamide; MTX, methotrexate; NRI, nonresponder imputation; RTX, rituximab. With permission from Edwards and coworkers [5]. Copyright ^© 2004 Massachusetts Medical Society. All rights reserved.

Figure 2

Rituximab in rheumatoid arthritis. Phase IIa: changes in total rheumatoid factor (median). CTX, cyclophosphamide; MTX, methotrexate; RTX, rituximab. Data from Edwards and coworkers [5] and from Emery and coworkers [6].