Rheumatologists need to “get creative” while treating rheumatoid arthritis, according to Dr. Daniel Furst, a Carl Pearson Professor of Medicine and director of the Rheumatology Clinical Research Center at the University of California Los Angeles School of Medicine. To spur on creative therapeutic solutions for the disease, rheumatologists need to combine therapies to address patients with symptoms that are difficult to resolve.
According to Furst, these combinations include the use of disease-modifying anti-rheumatic drugs (DMARDs) and biologic therapies — some of which are more suitable than others, depending on the efficacy and side effects for each specific patient.
“You want to look at mechanisms that do not overlap, and you want to look at toxicities that do not overlap,” noted Furst in his presentation at the American College of Rheumatology State-of-the-Art Clinical Symposium.
As an example, Furst talked about sulfasalazine and methotrexate, both of which overlap in their mechanism of action in treating people with rheumatoid arthritis. However, there is less of an overlap between cyclosporine and abatacept, as well as between tofacitinib and tumor necrosis factor-alpha (TNF-a) inhibitors.
“When you do not have overlap of mechanisms, you have higher probability that they will work together and be additive to each other, not work against each other. This isn’t infallible, but it is a reasonable way to approach it,” he added.
The same approach is used with determining toxicity. Cyclosporine and methotrexate have overlapping mechanisms of action, but they do not overlap in terms of toxicity, and they can work quite well together, according to the researcher. In turn, tocilizumab and methotrexate do not present problems with toxicity, but very little improvement in patients was observed when this combination was used.
“In this case, the idea of non-overlap means we might not get the kick that we might get with TNF inhibitors plus methotrexate,” noted the researcher. In addition, there are cases in which medications seem to even work against each other.
For patients who have not responded well to several other prior treatments, or for those who have responded at first only, Furst suggested the combination of abatacept and cyclosporine, and later to add tofacitinib.
“We are adding some pretty strong drugs, but there should not be overlap of mechanisms and, even though the data are not there, it is something to do in this patient in whom nothing seems to work,” Furst concluded.
