In the pre-biologic era, there was a subgroup of patients with rheumatoid arthritis (RA) receiving MTX who appeared to be in remission but still had progressive joint damage. These patients were a challenge to treat, as it can be difficult to identify someone who may clinically respond but is going to have progressive structural damage. There was some hope that biomarker assays, such as the multi-biomarker disease activity score, could do this, although their clinical benefit has been limited and we have never been able, proactively identify such patients very well. These types of concerns have largely faded with the advent of biologic therapy. Post hoc analyses of studies with tumor necrosis factor inhibitors have shown that there is virtually no correlation between the degree of response (eg, ACR20, ACR50, ACR70) and radiographic progression. If patients have any type of clinical response to biologics, then they have significant inhibition of progression of radiographic damage. In contrast, with MTX, an effect-response relationship was observed, with a better clinical response associated with less radiographic progression. Thus, the use of MTX is more challenging and has resulted in patients having a very low threshold for moving on from MTX to biologic therapy.

My personal approach is to target disease remission in patients on MTX monotherapy; if they are only in a state of low disease activity, then you have not done your job as a rheumatologist. Patients who are not in remission are clearly at a higher risk for structural progression and are likely at a higher risk for cardiovascular complications. Thus, if a patient cannot achieve remission on MTX monotherapy, I add a biologic. On the other hand, once a patient is on a biologic, I am not certain that there are adequate data to suggest that going from low disease activity (eg, slightly above target) to remission will improve structural outcomes. If, in that situation, the patient is happy with their treatment response, then there is not much evidence to tell me that I should adjust or accelerate their therapy. Certainly, in terms of structural damage, that approach is likely adequate. Overall, my ideal treatment goal for patients with RA is to make them feel as though they do not have the disease; a medical student should be able to examine patients and determine that they do not have any signs of RA. A challenging scenario is the patient who is currently in remission while at the office visit but is having flares between visits. The challenge is to figure out how significant the flare is and whether it is severe enough to warrant different long-term therapy. This is an area of ongoing research.