Patients under the care of the U.S. Veterans Affairs who were older, non-white and had more comorbidities were less frequently given biologic initiation therapy to treat their rheumatoid arthritis (RA), according to a recent study.
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Explore This IssueDecember 2018
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Researchers sought to identify predictors of greater use of biologic therapies, as well as factors associated with persistent use of glucocorticoids, in patients with RA. Results of the large cohort study, which reviewed a decade of data, were published in The Journal of Rheumatology.1
“What stands out is that there are big differences in how [physicians] treat older and sicker versus younger and healthier patients,” says study author Michael George, MD, MSCE, a rheumatologist and instructor of medicine at Penn Medicine, a division of the University of Pennsylvania, Philadelphia.
The use of biologics raises questions of the possibilities of both undertreatment and overtreatment of patients with RA, note the authors. Those scenarios can change depending on access and treatment patterns.
Some patients whose disease could be controlled with conventional disease-modifying anti-rheumatic drugs may wind up being overtreated, while those who continue strictly with conventional treatments despite active disease could be undertreated, which can lead to chronic use of glucocorticoids, according to the authors.
“The goal would be to get people on the therapy they need right off the bat, as opposed to a trial-and-error [approach to] find the exact therapy someone needs,” explains Dr. George.
“For now, we don’t have a good way of predicting who is going to need which treatment and that’s why there is often a step-up approach, starting with methotrexate and then adding other medicines to it, like a biologic,” he says. “If that doesn’t work, we try a different one.”
Researchers gleaned clinical and administrative information from three U.S. Veterans Affairs databases spanning from 2005–16 to identify patients with RA who were receiving a first-ever prescription of methotrexate. To identify an inception cohort, the study required patients to have six months or more of baseline data within the VA system before the first methotrexate prescription.
Study criteria were designed to include a homogenous group of patients with RA that was severe enough to be prescribed methotrexate. Selecting a population with newly initiated methotrexate therapy enabled researchers to study patients at a similar phase of their disease who were first treated with methotrexate, considered the backbone of treatment for RA.
“People define early [biologic] use differently,” says Dr. George, explaining the study did not include patients who began biologics first, before any other type of therapy. “We were taking the more common situation of people who are starting methotrexate. … They are probably relatively early on in their disease.
“Then we look out two years to ask, ‘Who are the people who are going to go on to start a biologic within that time frame?’”
Of 39,789 patients who had a diagnosis of RA and a first prescription of methotrexate, there were 17,415 who met all inclusion criteria. Among the patients included in the study, 45% were 65 years or older, 88% were men, and 73% were white, according to the article.
Compared with the youngest group in the study, patients 65–80 years old were 58% less likely to get a biologic & those 80 or older were 80% less likely to get a biologic.
Almost half of the cohort (49%; 8,465 patients) received glucocorticoids at baseline, with a similar frequency across age groups. Greater use was seen in patients with higher Charlson comorbidity scores, depression, asthma and other respiratory conditions, and those treated concomitantly with hydroxychloroquine.
There were 3,263 patients in the study who received biologic therapy within two years of starting methotrexate, a cumulative incidence of 12.6% at one year and 20.6% at two years, according to the article. Results revealed biologic use decreased as the age of each group increased and was dramatically lower in older and non-white patients, as well as those with a greater comorbidity burden.
Compared with those who were younger than 50 years old, patients who were 50–65 were 26% less likely to get a biologic, according to the study. Patients 65–80 were 58% less likely to get a biologic and those 80 or older were 80% less likely to get a biologic compared with the youngest group in the study.
“We were surprised by how dramatic those findings were,” says Dr. George. “Even people just 65 and above were much less likely to be treated with a biologic therapy. It was really a very dramatic difference by age.”
Dr. George says a number of reasons may explain why older patients are less likely to be treated with biologics than younger people. It could be patient preference—older patients may resist trying newer therapies—for example. Another possibility is that physicians worry about infection or side effects in older populations, given that biologics used to treat the disease often come with a black box warning of serious risk of infection.
The finding that non-white patients get biologic treatment with less frequency is something that has been shown in previous studies, as well, says Dr. George. Why this occurs, although not addressed in the study, is an area of great importance that deserves further investigation, he says.
“There’s a lot of variation in how we are using biologic therapies,” says Dr. George.
“Patients who are older and patients who have other health problems are much less likely to be treated with a biologic therapy than patients who are younger and healthier,” he says. “But when we look at the alternative, we find that these patients are just as likely or more likely to be treated with prednisone, even though that might potentially be riskier.”
Treatment guidelines recommend conventional therapy be used first, before use of a biologic for patients with serious infection is considered, says Dr. George. Another piece of the puzzle to consider is the use of steroids.
Prednisone and other glucocorticoids are commonly used to effectively treat symptoms of RA, but even at moderate doses they have substantial side effects and safety issues, says Dr. George. Patients using long-term doses of prednisone above 10 mg a day could be at risk of infection, weight gain, diabetes, osteoporosis and other adverse outcomes.
Future research needs to look at the tradeoffs between prednisone and biologic use for healthy people and people who are sicker and older, says Dr. George.
“The treatment for rheumatoid arthritis has really been revolutionized in the past two decades,” says Dr. George. “We have an ever-expanding number of options to treat rheumatoid arthritis. [Treatment is] much more effective than in the past, but all medications come with some potential for side effects. So the challenge is to figure out how to best use these medications to make people better, but at the same time maximize safety.”
Catherine Kolonko is a medical writer based in Oregon.
- George MD, Sauer BC, Teng CC, et al. Biologic and glucocorticoid use after methotrexate initiation in patients with rheumatoid arthritis. J Rheumatol. 2018 Oct 1.