One scenario of a difficult-to-treat patient really comes from the active inflammatory disease. This could be a patient with RA who is started on the ladder of treatment advancement, beginning with methotrexate, then a biologic, and then required a change in biologic—perhaps even several changes in biologics—and then, possibly, a small molecule. That is a challenging case for a rheumatologist, and the strategy there is to keep trying, and you may have to change the medication every 3 to 4 months until control of really active inflammatory disease is achieved. 

Then there is the patient whose joints and other indices seem to be improving and getting under control, but in whom there may be an issue with central sensitization, causing pain that is more widespread and “fibromyalgia-like.” So, in this case, there is pain augmentation. The question is, do rheumatologists recognize this process as well as we should? In this type of case, the approach may be different in that it may require additional treatment modalities: some counseling, physical moves, motivation, mobilization, and, perhaps, some agents that act upon the central nervous system in an attempt to resolve those issues. 

If we consider excessive pain and fatigue and intercurrent mood disorders in RA, we know that mood disorders are reported in a higher frequency in patients with RA than in the general population. Patients with mood disorders and central pain may not track directly with core indices of tender and swollen joints and inflammation.

Another issue is that we often do not spend a lot of time talking to our patients about depression because we find individuals with RA to be quite robust and resilient. We have always known that, for some reason, they seem to be able to endure more issues than patients with other types of arthritis. So, what we have been looking at now is whether patients with depression respond similarly to those without depression. This involves the use of certain surrogate markers, such as the 36-Item Short Form Health Survey, self-rated health, and health-related quality of life. We are just at the beginning of really trying to understand this, but it looks as if consistent responses in patient-reported data can be indicative of depression, and that these patients who we think may have depression are still able to respond just as well to RA therapy as other patients without depression or who may have less-severe depressive symptoms.