Unmet Needs of Rheumatic Diseases

Sergio Schwartzman, MD: I think that the next quantum change in the management of patients with rheumatic diseases is not going to be a new drug. I think that the next quantum change will be personalized medicine. The way that personalized medicine will ultimately function is that we will have either biomarkers, or cytokine markers, or genetic markers, that will give us approximations as to what the likelihood of success with a given therapy will be. So, if I have a drug that’s approved for rheumatoid arthritis or psoriatic arthritis that has a 90% chance of being effective, I’m much more likely to use that than a drug that has a 30% chance of being effective. It’s been a challenging arena with regard to creating these biomarkers or genetic markers to predict response but one that obviously is generating a lot of research.

The other point that I would make about these biomarkers—and something that’s not frequently spoken about, but I think is as important as predicting response—is it’s important to predict safety. If I have this same therapy that has a 90% chance of being effective in a patient with rheumatoid arthritis but has a 95% chance of being associated with a serious infection, even though it’s going to be very effective, there’s no way that I’m going to use it. These biomarkers that we’re looking to develop have to address not only efficacy but safety, which is just as important. When that era comes, I think it will make the management of our rheumatic diseases much easier.

Co-manifestations and comorbidities are different, or at least I think of them as different entities. Let’s take rheumatoid arthritis as an example. A comorbidity of rheumatoid arthritis is the consequence of having an active inflammatory disease that’s not being controlled. For example, in rheumatoid arthritis, I would argue that a comorbidity would be osteoporosis or premature cardiovascular disease. Whereas, a co-manifestation is a distinct separate entity that may or may not be related to inflammatory disease. A co-manifestation of rheumatoid arthritis would be scleritis, the disease in the eye that now is infrequently seen because we manage rheumatoid arthritis so much better.

Since these conditions, the co-manifestations, are not that frequent, they’re not usually parts of clinical trials. We do have to understand that particularly with regard to co-manifestations, there are different responses to different approved therapies. If we continue with the concept of scleritis as an example in rheumatoid arthritis, there are data, for example, that rituximab—the B-cell targeted therapy—is effective in patients who have scleritis. Whereas, there’s not much data for targeted synthetics or other cytokine-driven therapies. There are case reports but not very much.

With regard to these co-manifestations, I think the rheumatic disease therapeutic landscape differs depending on which co-manifestation you are talking about. Comorbidities are really more, at least in my mind, a consequence of uncontrolled inflammation. Therefore, if you control the disease process, you’re less likely to have them. Premature cardiovascular morbidity is affected by controlling the disease process and maybe equally affected by different types of therapies. Same thing with osteoporosis.

Transcript edited for clarity.