Monoclonal antibody treatments for rheumatoid arthritis
Department of Medicine, Division of Infectious Diseases and Immunology
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
Expert opinion on biological therapy
Bossaller, Lukas and Rothe, Achim, "Monoclonal antibody treatments for rheumatoid arthritis" (2013). University of Massachusetts Medical School Faculty Publications. 380.