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October 10, 2020
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'Newer meds' have opened the door for 'newer concepts' in treating RA

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While the broad range of available therapies to treat rheumatoid arthritis provides clinicians with options, there is still no clear-cut treatment algorithm for every patient, according to a presenter at the 2020 Congress of Clinical Rheumatology-West.

Arthur Kavanaugh, MD, professor of medicine at the University of California, San Diego, suggested that “newer meds” — namely, biologics and biosimilars — have led to “newer concepts” in treating the disease. “We have lots of choices, almost too many, so that we do not know how to use all of them,” he said. “But we are doing much better than we ever have before in RA.”

Source: Adobe Stock.
“TNF has been a very important target,” Arthur Kavanaugh, MD, told attendees. “The success we have seen in the clinic with TNF inhibitors has changed our approach to rheumatoid arthritis.”
Source: Adobe stock.

Kavanaugh stressed that having too many therapies is generally a good problem to have, particularly for rheumatologists, but that EULAR and other guideline documents do not contain clear algorithms. “Many of us rheumatologists tend to be ornery,” he said. “We like to mess around with things, and we do not like to follow an algorithm.”

With that in mind, Kavanaugh provided an exhaustive review of the drugs in the RA armamentarium.

Arthur Kavanaugh

“We generally start with methotrexate,” he said, describing the drug as the “anchor” of RA treatment.

In the event of poor response to methotrexate, EULAR recommendations suggest that a TNF inhibitor should be next in line. “TNF has been a very important target,” Kavanaugh said. “The success we have seen in the clinic with TNF inhibitors has changed our approach to rheumatoid arthritis.”

Turning to disease-modifying antirheumatic drugs (DMARDs), 2020 saw a lot of attention focused on hydroxychloroquine. “It is either the cure or the death of you,” Kavanaugh said. “This caused us to have discussions about the role of it.”

Kavanaugh said it has a role in RA largely because of its safety profile. “It is still a choice for people who have concerns about liver or kidney toxicity,” he said. “But we still have to answer questions about dosing.”

A further point to consider is that hydroxychloroquine can be beneficial as part of “triple therapy” with methotrexate and methyl sulfasalazine, according to Kavanaugh.

Beyond hydroxychloroquine, biologics have also received a lot of attention in recent years, according to Kavanaugh. He suggested that the T-cell modifier abatacept (Orencia, Bristol Myers Squibb) may be attractive due to its safety profile. However, caution is warranted. “We discovered in 2020 that getting rid of all T cells is not helpful in RA,” he said.

Kavanaugh suggested that rituximab (Rituxan, Genentech) presents an interesting case because it is used as second-line therapy much more commonly in Europe and other parts of the world than it is in the U.S. “There have been some recent data showing that B cell therapy may be incredibly important,” he said.

While three JAK inhibitors are currently approved for use in the U.S. — with more such approvals on the way — Kavanaugh warned that further investigation is warranted. “As much as we understand [about JAK inhibitors], there is still much that we still do not understand when it comes to using these molecules,” he said.

Biosimilars are similar to rituximab in that use in Europe and other parts of the world is much more prevalent than it is in the U.S. That said, if there was one overarching concern for Kavanaugh, it pertained to switching from the bio-originator to the biosimilar. “Those concerns have been allayed” by recent data sets, he said.

When it comes to tapering or continuing low-dose prednisone, Kavanaugh suggested that there is a “Rorschach” effect. “Depending on the physician and the patient, some may view that tapering is effective, while others believe that ongoing low-dose glucocorticoids can keep flares at bay,” he said.

Kavanaugh said he would be remiss if he did not address COVID-19 in the context of RA. The general message is that it is “not unreasonable” to continue medications, rather than discontinuing treatment in patients who are at risk or who have the virus, with the understanding that the clinical and research communities are still searching for answers. “Maybe it is a good option to control systemic inflammation” in RA among patients with COVID, he said.

Overall, Kavanaugh urged clinicians to stay up to date in order to optimize outcomes. “We need to look at the data, interpret the data, and then bring [treatments] to patients to improve the disease,” he said.