What are the potential inflammatory interfaces that are affected by inhibition of the IL-6 cytokine pathway? How does each pathway potentially affect clinical manifestations of RA?
Are IL-6 inhibitors synergistic with methotrexate and how do they compare to TNFIs as far as their efficacy as monotherapy in patients with RA?
What is the precise immunopathobiologic mechanism of action (MoA) for agents targeting IL-6 in the setting of RA? How does IL-6 affect bone loss in RA?
What adverse effects should clinicians be aware of when treating RA patients with IL-6 inhibitors?
What are the risks for infection when treating RA patients with biologics?
What metabolic or hematologic markers should we monitor in patients on IL-6 therapy?
What is your assessment of the cardiovascular risk profile associated with IL-6 therapy? And the possible role of IL-6 inhibition as a mitigator of any effects related to LDL elevation?
When a suboptimal clinical response has been encountered with a traditional DMARD, what therapeutic approaches for escalating therapy are appropriate?
When a suboptimal clinical response has been encountered with TNF, do you recommend switching to a biologic with a different MoA, such as an IL-6 inhibitor or co-modulating agent?
Among the biologic agents, are there any significant efficacy or safety differentiators that prompt you to deploy one agent in preference to another, in any particular sequence?
How long of a trial using traditional DMARD therapy with methotrexate do you recommend prior to intensifying treatment with a biologic agent?
What are the strategies for individualizing treatment in patients with RA?