Resetting Immune Tolerance for the Prevention of RA

Moderator(s)

• WR

  William Robinson, MD, PhD

  Stanford University

Speaker(s)

• 

  Ronald F Van Vollenhoven, MD, PhD

  Amsterdam UMC
• PT

  Peter Taylor, MD, PhD, MA

  University of Oxford
• 

  V. Michael Holers, MD

  University of Colorado

Rheumatoid arthritis (RA) has been postulated to develop in several phases; with inherited susceptibility factors in some cases leading to asymptomatic (or preclinical) citrullinated protein-directed autoimmunity, followed after some interval by the development of synovial infiltration and polyarticular disease. Yet, it is controversial whether progression to overt disease is uniformly unavoidable. In these presentations, different perspectives on preclinical autoimmunity will be presented. Rationales will also be discussed for the selection of agents with different mechanisms of action (MOA), proven for the treatment of active RA, and for arresting or even reversing pathogenesis at the preclinical stage. Faculty will then review interim progress in evaluations of rituximab, hydroxychloroquine and abatacept in individuals with preclinical autoimmunity, as well as also consider the merits other, potential interventions suggested by ongoing studies of the pathogenesis of preclinical RA. Our program will conclude with an interactive panel discussion.

Learning Objectives:

• Discuss the predisposing factors postulated to contribute to the progression of RA in distinct phases
• Explain evidence, from preclinical animal models and retrospective serologic studies, of the pathogenic mechanisms responsible for the development of preclinical autoimmunity and subsequent overt disease
• Consider the mechanisms of action of selected therapeutic agents that are attractive for use in early phase intervention clinical studies
• Review interim results in controlled intervention trials, when available, and consider the feasibility for inducing therapeutic healing of disease-associated breaches in immune tolerance

Presentations:

• 3:00 PM – 3:15 PM ET

  Targeting B-cells to Nip Autoimmune Diseases in the B(ud)?
  Ronald F Van Vollenhoven, MD, PhD – Amsterdam UMC
• 3:15 PM – 3:30 PM ET

  Co-Stimulation: A Pathway to Prevention?
  Peter C. Taylor, MD, PhD, MA – University of Oxford
• 3:30 PM – 3:45 PM ET

  Transitioning from “RA Drugs” Today to Mechanism-Based Interventions Tomorrow
  V. Michael Holers, MD – University of Colorado
• 3:45 PM – 4:00 PM ET

  Panel Discussion & Q&A