Monoclonal antibody treatments for rheumatoid arthritis
Department of Medicine, Division of Infectious Diseases and Immunology
Medical Subject Headings
Antibodies, Monoclonal; Arthritis, Rheumatoid; Biological Products; Clinical Trials as Topic; Drug Evaluation, Preclinical; Humans; Protein Engineering
Amino Acids, Peptides, and Proteins | Immune System Diseases | Immunoprophylaxis and Therapy | Musculoskeletal Diseases | Therapeutics
INTRODUCTION: Rheumatoid arthritis (RA) is a systemic disease and the most prevalent of all autoimmune disorders. Here we review recent advances in the development and availability of biologic agents with a focus on monoclonal antibody or smaller formats of targeted engineered therapeutics including novel, non-antibody-based therapeutics.
AREAS COVERED: Today an array of biologics blocking either proinflammatory cytokines or lymphocyte activation/survival are available that enable a substantial improvement over conventional disease-modifying antirheumatic drugs (DMARDs). We review the engineering process of antibody-based biologics, their preclinical and clinical application, and current efforts to treat RA by interfering with B-cell function (notable targets covered are CD20, CD38, B-cell activating factor, transmembrane activator and calcium-modulating and cyclophilin interactor), with T-cell function (CD3, CD4, CD28), with bone erosion (RANKL), and with cytokines or growth factors (tumor necrosis factor, interleukin-1 [IL-1], IL-6, IL-17, VEGF). Future treatment choices might encompass the blockade or modulation of danger-associated molecular patterns such as HMGB1, pattern recognition receptors, messenger RNAs or noncoding RNAs, histone acetylation, and inflammasome components.
EXPERT OPINION: Although current therapies can reduce the signs and symptoms of RA for many patients, the quest for a cure (or a more complete blockade of the structural damage) in RA is still ongoing and will need treatment approaches, which are not exclusively confined to blocking a particular cytokine, receptor, or autoreactive B or T cell involved in disease progression. To this end exciting treatment alternatives and drug targets are on the horizon that may become available to patients in the future.
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Citation: Bossaller L, Rothe A. Monoclonal antibody treatments for rheumatoid arthritis. Expert Opin Biol Ther. 2013 Sep;13(9):1257-72. doi: 10.1517/14712598.2013.811230. Link to article on publisher's site
Bossaller, Lukas and Rothe, Achim, "Monoclonal antibody treatments for rheumatoid arthritis" (2013). University of Massachusetts Medical School Faculty Publications. 380.