For patients with established rheumatoid arthritis and moderate to high disease activity who are unresponsive to TNF inhibitors, what is recommended?

When dealing with persistent moderate to high disease activity in patients with established rheumatoid arthritis who have not responded adequately to TNF inhibitors, the recommended approach is to initiate a non-TNF biologic. This strategy is based on the understanding that if a patient does not respond to one class of biologics, such as TNF inhibitors, switching to a different class can provide a better therapeutic outcome. Non-TNF biologics, such as IL-6 inhibitors (like tocilizumab) or B-cell depleting agents (like rituximab), offer mechanisms that may address the underlying disease processes that are not affected by TNF inhibitors.

Other options, such as simply increasing the dosage of the TNF inhibitor, are less supported because the lack of response indicates that the pathway targeted by TNF inhibition may not be adequate for that patient. Changing to methotrexate alone does not address the need for more aggressive therapy in the context of ongoing significant symptoms and inflammation. While corticosteroids can provide rapid relief for inflammation, they are typically not the first choice for long-term disease management due to potential side effects and do not modify the underlying disease course. Switching to a non-TNF biologic provides an opportunity to target different pathways involved in the inflammatory processes