What is the precise immunopathobiologic mechanism of action for agents targeting IL-6 in the setting of RA? Are these MoAs synergistic with other MoAs? If so with which other agents should IL-6 targeting agents be used?
What are accepted treatment triggers for employing disease-modifying anti-rheumatic drugs (DMARDs)? And what classes of biologic agents — including IL-6 inhibitors and others — have demonstrated efficacy as monotherapy?
What new data related to the use of TNFIs and the use of IL-6 inhibitors do we have as it relates to drug persistence and safety profiles?
How does the IL-6 pathway and family of cytokines affect inflammation and non-joint clinical manifestations?
What biomarkers, clinical findings, or previous treatment history do you rely on to identify patients who might be uniquely responsive to IL-6 inhibition?
Can you discuss the unique mechanistic effects of IL-6 inhibition — including the role of GP 130 — that differentiate it from other cytokines that are targeted in RA? Can its signaling properties be transmitted to sites distal from inflammation?
Is there a systematic approach for aligning specific cohorts of patients with RA with specific therapies? With IL-6 inhibitors, TNFIs, or co-modulating activating agents?
What disease activity measures for RA do you consider to be most important?
Can you compare the translational implications of inhibiting the TNF vs IL-6 cytokine signaling systems? How are these differences manifested clinically?
When are combination approaches — with a DMARD and biologic — used to treat RA and when might monotherapeutic approaches be preferable?
What percentage of patients started on a TNFI will respond and to what degree will they respond?