ATLANTA—When it comes to treating rheumatoid arthritis (RA) patients, most clinicians agree: One size does not fit all. Many treatment options exist, and seldom is there 100% consensus on what the first course of action or general approach should be.
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In the face of such variability, four clinicians took the stage at the 2019 ACR/ARP Annual Meeting in front of hundreds of their peers to answer questions—and face scrutiny over their answers—without prepared scripts or PowerPoint slides to guide them:
Joan Bathon, MD, a professor of medicine and chief of the Rheumatology Division at Columbia University College of Physicians and Surgeons, New York;
Vivian Bykerk, MD, FRCPC, director of the Inflammatory Arthritis Center of Excellence at the Hospital for Special Surgery, New York;
Paul Emery, FRCP MA, FMedSci, a professor of rheumatology at the University of Leeds and director of the Leeds Musculoskeletal Biomedical Research Centre at Leeds Teaching Hospitals NHS Trust, United Kingdom; and
Ted Mikuls, MD, the Umbach professor of rheumatology at the University of Nebraska Medical Center, Omaha, where he also serves as vice chair of research for the Department of Internal Medicine.
A Hypothetical Case
The clinicians were asked to diagnose and prescribe therapy for a 55-year-old female executive. She was fit and in good health, but had experienced two months of polyarthritis and stiffness, and was seropositive for rheumatoid arthritis. Would they start with a biologic or targeted treatment rather than methotrexate?
Dr. Emery said he would first evaluate the likelihood of success with methotrexate. If the indicators are the patient won’t do well on methotrexate, he said, “I’d recommend starting with combination therapy.”
“I almost never start with a biologic only,” said Dr. Bathon. “One exception is for women who plan on becoming pregnant. That would not be a concern for this patient. The only other situation [in which] I would consider a biologic early on would be in the situation Dr. Emery said: in a patient with predictors of severe erosive disease. Then I would use the biologic with methotrexate,” she said.
Barring contradictions, Dr. Mikuls said he would start with a biologic in only one instance in such a patient: “When hell freezes over. I would almost always use methotrexate first line in this patient.”
What About Corticosteroids?
The panelists were asked about bridging with prednisone. Dr. Emery said in 80% of cases he would prescribe steroids. “We use bone density as a biomarker of poor outcome, and the patients who actually suppressed their inflammation with steroids, gained bone,” he said. “I think you want to get patients well as quickly as possible, so we would use steroids short term. But all recommendations are to use them for the minimum term possible.”
Dr. Bathon said she’s not as keen on using steroids. “I do use them for the patient where their disease activity is so severe they’re disabled and can’t wait for methotrexate to kick in. I start them on prednisone—20 mg is the highest I use—and I taper it down over a month or so.”
“It’s a clinical decision based on the patient,” said Dr. Mikuls. “There are patients in our clinic that really need [prednisone], are losing productivity at home or at work, and need something to help while methotrexate takes effect. Usually, you can get rid of that within a few months. But I often have patients who absolutely don’t want steroids.”
Dr. Bykerk mentioned the tREACH study (i.e., Treatment in the Rotterdam Early Arthritis Cohort), which found that oral or intramuscular glucocorticoids were equally effective as bridging therapy for these patients. “The study found no differences between oral or intramuscular glucocorticoid bridging therapies, nor any differences in serious adverse events,” she said. “The problem with oral steroids is [the patient may] end up liking them too much.”
Patients with Cancer
The panelists were asked if malignancy colored their biologic choice.
Dr. Emery said that in the United Kingdom, they’ve had official guidelines for some time, “and anti-TNF [tumor necrosis factor], by its very name, suggests perhaps you shouldn’t use it [in] people with tumors—and we didn’t use it for five years. Now, our registry [results] are relatively reassuring that patients who have recurrences of cancer on biologics aren’t more frequently at risk than on conventional DMARDs [disease-
modifying anti-rheumatic drugs].”
Dr. Bathon said she basically agreed. “But sometimes there’s confusion that TNF inhibitors are discouraged for people with cancer. The databases negate a lot of that concern, but what people sometimes mistakenly think is if they avoid a TNF inhibitor, because of the potential association with malignancy, it’s safe to use all the other biologics instead. Safety datasets for those aren’t robust, so I don’t think we should extrapolate to say those are safer in patients with malignancy.”
Dr. Mikuls said not all malignancies are created equal. “With hematologic malignancies, I’m going to be more worried about anti-TNF. But Paul is absolutely right: The long-term observational data make us feel pretty good about anti-TNFs, particularly out a ways from malignancy.”
Dr. Mikuls said that with melanoma patients, he’d be worried about abatacept, “given what we know about checkpoint inhibition. So it depends on the cancer, and it’s always an ongoing risk-benefit analysis in the clinic with patients about these therapies.”
“I think it is a complicated question,” Dr. Bykerk said, “but there are many systematic reviews right now that suggest that with a solid malignancy you might want to wait a while [before starting an anti-TNF].”
The panelists were asked about precision medicine; specifically, where did they think this area of research is going?
“Finding the right therapy for the right person at the right time—at the beginning—
would make a huge difference,” said Dr. Emery. “For example, we spend a lot of time trying to predict methotrexate response and anticipate the nonresponders.”
“I think our precision treatments are much more advanced than our ability to determine which ones we should use,” said Dr. Bathon.
“Using just histology at baseline—for when you want to switch therapy—is not yet mature enough,” said Dr. Bykerk. “We need to understand the markers and that work is being done right now.” (Note: Dr. Bykerk has been involved with the Accelerating Medicines Partnership since 2014 to better understand the pathophysiology of RA.)
“There’s a lot of interesting research, but the question remains, ‘Is precision medicine where we all want it?’ It’s an obvious ‘no,’” Dr. Mikuls said. “We have a lot of work to do in that arena. It’s an exciting time, and I hope that in the next five to 10 years we’ll get there.”
Mike Fillon is a healthcare writer living in the Atlanta area.