Rheumatoid Arthritis: Biologic Agents

Dr. Larry Moreland is the Margaret J. Miller Professor of Arthritis Research and Chief of the Division of Rheumatology and Clinical Immunology at the University of Pittsburgh. In addition, he has also been a consultant to Biogen/IDC, Genetech, Eli Lily, Incyte, and UCB in the last 12 months. Objectives for this presentation included identifying biologic agents in the use of RA; discussing the role of TNF inhibitors in rheumatoid arthritis; describing the role of B-cells in rheumatoid arthritis; and discussing what advances need to happen in order to better treat this condition. The case study for this particular presentation dealt with a patient named "LG," a 52-year old woman presenting with a four month history of additive symmetrical polyarthritis, whose "incapacitating" pain forced her to quit her job. The following information is comprised of highlights from this presentation.

Lessons Learned and Unmet Needs Regarding TNF Inhibitors for Rheumatoid Arthritis

- THNF inhibitors have proven to be effective. In fact, 50-66% of patients have ACR 50 when combined with MTX.

- Mechanisms of actions and kinetics in humans have shown to vary with different agents. Mechanisms of 1° and 2° failure are the primary focus of research interest.

What Are Some of the Roles of B-cells in Rheumatoid Arthritis?

- Activated B-cells secrete cytokines.

- B-cells may function as APCs in the synovium - this may result in T-cell activation.

- Activated B-cells differentiate into plasma cells and secrete immunoglobulins.

Rheumatoid Arthritis Therapy in 2009: What Are We Missing?

- Anti-TNF failures (mechanisms)

- Biomarkers that are able to predict the need for combination therapy as an initial treatment.

- Biomarkers that are able to predict long-term prognosis and consequently guide early therapeutic drug options.

- Pathology in the individual patient (ie, Rheumatoid Arthritis as a heterogenous disease)

Key references for this presentation included the following two sources:

The American College of Rheumatology 2008 Recommendations for the use of nonbiologic and biologic-disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum 2008; 59:762-784.

New Therapies for treatment of rheumatoid arthritis. Lancet 2007; 370:1861-1874