title: Monoclonal antibody treatments for rheumatoid arthritis.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Massachusetts Medical School, Division of Infectious Diseases and Immunology, Worcester, MA, USA. Lukas.Bossaller@umassmed.edu
authors.forename: Lukas
authors.initials: L
authors.lastname: Bossaller
authors.forename: Achim
authors.initials: A
authors.lastname: Rothe
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000628:therapy*; D001688:Biological Products / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D006801:Humans; D015202:Protein Engineering
chemical_list: D000911:Antibodies, Monoclonal; D001688:Biological Products