Targeting Novel RA Pathways Within the Cell: At the Cutting Edge of Therapy

Introduction/Background

JAK-STAT Pathway: Basic Operation

Discovery of the JAK-STAT Signaling Pathway

Complexity of Response to IFN Gamma: JAK/STAT Activation

JAK-STAT Pathway and Cytokine Signaling

Cell Communication

The JAK-STAT Pathway Is a Prime (and Primordial) Extra- and Intra-Cellular Communications Pathway

Evolutionary Conservation of the Physiologic Roles of the JAK-STAT Pathway: The Drosophila JAK/STAT Pathway

The Human Canonical Model of JAK-STAT Signaling

Cytokines, Factors, and Intracellular Signaling Components Implicated in the Pathogenesis of RA

Pathogenesis of RA: Triggers and Epigenetic and Post-Translational Disease-Related Modifications

Immune and Inflammatory Responses: Pathogenesis of Synovitis Characteristic of RA[a-c]

Cytokine Profiles That Subserve the Biology of Discrete Phases of the RA Disease Process

Many Cytokines and Growth Factors Converge on the JAK Signaling Pathway[a-c]

Cytokine Pathways and Blocking Agents: One Target at a Time[a-b]

The Biological Significance of Signaling Through Different JAK Combinations: Multiple Pathophysiologic Targets[a-d]

Elevated STAT3 Expression in Patients With Early RA

Stratifying Non- or Inadequate- Treatment Response in RA

Tofacitinib JAK 1 and JAK3 Inhibitor: Clinical Trial Results in RA

Baricitinib: Key Studies in RA Phase 3 Program and Their Characteristics

Topline Results for Baricitinib: RA-BEAM and RA-BUILD

RA-BEACON: Baricitinib in RA Patients With an Inadequate Response to TNF-Alpha Inhibitors

Patient-Reported Outcomes: RA-BEAM Phase 3 Trial of Baricitinib

Filgotinib: Results From the DARWIN 2 Trial

Summary and Conclusions

Abbreviations

Abbreviations (cont)

Abbreviations (cont)

Abbreviations (cont)