VIDEO: Biggest challenges in RA treatment

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First of all, I think that we struggle with patients who experience recurring infections in the setting of their immunosuppressive disease modifying therapies for rheumatoid arthritis. We still encounter people who have recurring skin or soft tissue infections. This often occurs in people who have other comorbidities. Part of that's just advancing age, or if they also happen to have Type II diabetes, or other factors that raise risks of skin and soft tissue infections, that can be a really complex situation. And sometimes it feels like, what are we really gonna do? We're having to weigh the decision of either stopping RA treatments or at least considerably scaling down the intensity of RA therapy against the burden of the disease, and pain, and suffering, and stiffness, and joint damage that may progress if we're not treating, and so those still are challenging patients. Fortunately, they're only a small subset of the overall population, but they're a very challenging subset to handle. The second example are patients with rheumatoid arthritis who have chronic lung disease, and that can be in the form of interstitial lung disease or obstructive lung disease, and patients with lung disease in the setting of RA can be very challenging. There is a lack of evidence supporting selection of any particular treatment, at least from clinical trials. We have some insights from observational studies, but of course, the evidence there is weaker than from clinical trials, so this could be a challenge, and many times we're trying to figure out, is it right to continue methotrexate? While historically that is thought to perhaps aggravate fibrosis in the setting of chronic lung disease, while more recent data suggests that perhaps methotrexate is a beneficial thing to continue in patients with lung disease. That's one example. The second is what biologic or targeted synthetic therapy may be best. And again, we really don't have trial insights to guide that. Some observational data suggests that abatacept may be one of the preferred therapies, and yet that may not always be effective for certain patients, or may not be as effective for their joint involvement as perhaps other options. And in some cases, that hasn't worked either, and so patients with lung disease can be quite challenging given the lack of evidence, and the tendency for lung disease in some subsets to progress and become very severe and hard to manage from the pulmonary standpoint. So that's a difficult subset, and the last subset I'll speak to are patients who have so-called difficult to treat rheumatoid arthritis. And this overlaps with the construct of refractory RA, that is patients who have failed perhaps two separate classes of biologic or targeted therapies for their RA, and experience persisting signs and symptoms of active rheumatoid arthritis. Sometimes that's truly due to refractory inflammatory disease, and in those patients we still see active swelling of joints due to underlying synovial inflammation, we may see persistent elevation of acute phase reactants, and those patients truly have refractory RA. In some situations, signs of active inflammation may be less evident and it merges with chronic pain in the setting of rheumatoid arthritis, which is also difficult to handle. Many times people like this also have a number of comorbidities that may be interfering with treatment, and that's part of why it's gotten to be difficult to treat. But truly, we still see people who have failed multiple classes. In some cases, it gets to be where they've essentially failed all our existing therapies and yet still are suffering from signs and symptoms of rheumatoid arthritis, and so I think that we still need to come to a mechanistic understanding of why some people are refractory to our existing therapies. Perhaps it's because we've gotten to a diagnosis late, or maybe we just have not used the right drug at the right time, and so all the while the disease becomes more refractory to treatment, or maybe there are, we still don't have all the the targets that we need to be able to treat, and so we need additional translational research to identify insights to those important questions.