THE OFFICIAL NEWS SOURCE OF ACR CONVERGENCE 2022 • NOVEMBER 10-14



Great Debate participants consider early use of low-dose corticosteroids for RA

In a lively debate Sunday about the use of low-dose corticosteroids in the initial six months of therapy for rheumatoid arthritis and in the first one-to-three years of therapy, Maarten Boers, MD, PhD, MSc, and Eric M. Ruderman, MD, presented research and arguments supporting both the pros and cons of the issue.

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Maarten Boers, MD, PhD, MSc

“I think continuous low-dose glucocorticoids should comprise part of the management of RA during the initial six months of therapy,” said Dr. Boers, Professor of Clinical Epidemiology at the VU Medical Center in Amsterdam. “The benefits are it works, the harms are very limited, and the costs are low.”
He called RA a glucocorticoid-deficiency disease.

“There is practically no disease in which glucocorticoids work as well as in rheumatoid arthritis in terms of improving signs and symptoms,” he said.

During The Great Debate: Long-term, Low-dose Corticosteroids Use in the Treatment of Rheumatoid Arthritis, Dr. Boers cited a number of clinical trials to support his arguments, including trials of the COBRA and COBRA-light strategies in treating RA. COBRA therapy consists of early, intensive RA treatment with the combination of high-dose prednisolone, methotrexate, and sulfasalazine.

COBRA light therapy consists of low-dose prednisolone starting at 30mg/day, tapered to 7.5mg/day in nine weeks and methotrexate escalated to 25mg/week in nine weeks. COBRA-light was found to be non-inferior to COBRA therapy in lowering disease activity and radiologic progression of disease.

As part of a study of COBRA-light therapy conducted at his medical center, 41 RA patients were randomized to receive either 60mg or 30mg of prednisolone a day as monotherapy before starting methotrexate.

“The most surprising finding was that after one week of steroids, nine patients regressed to normal glucose tolerance. The chance of regressing to normal was related to early intervention. The earlier the intervention, the more likely they were to revert to normal glucose tolerance,” Dr. Boers said.

As to the question of whether glucocorticoids should be continued beyond six months into the one-to three-year period of RA therapy, Dr. Boers also argued the affirmative.

“I think RA patients should be on very low doses of glucocorticoids, preferably forever,” he said. “Certainly, glucocorticoids should be a component of the 12- to 36-month management of RA.”

He pointed to statistics on current practice management behaviors, saying surveys reveal that at any given time, 30 to 80 percent of RA patients will be on low-dose glucocorticoids. Clinical trial data show that about 50 percent of RA patients included in trials are on glucocorticoids.

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Eric M. Ruderman, MD

In arguing against the use of low-dose corticosteroids in the first six months of RA therapy and in the subsequent one to two years of therapy, Dr. Ruderman, Professor in Medicine-Rheumatology at Northwestern University’s Feinberg School of Medicine in Chicago, cited studies showing no significant differences in radiographic progression or outcomes in RA patients with the use of corticosteroids compared with no corticosteroids.

“In the first six months of therapy, it’s all about risks versus benefits. The potential benefits of corticosteroid therapy are a reduction in disease activity and perhaps a reduction in structural damage,” he said.

He cited results of the CAMERA II trial, in which patients with early RA were treated with a tight control scheme of climbing dosages of methotrexate plus either 10mg prednisone daily or placebo. After the two years of the trial, 70 percent of the patients treated with the tight control strategy without glucocorticoids had no erosions versus 82 percent of the patients treated with additional prednisone.

“The patients who stayed on prednisone had improvement relative to those not on prednisone for six months or so, but not for the rest of the study,” he said. “I would acknowledge that prednisone can lead to more rapid improvement in disease during the first six months of therapy, but at what cost in terms of side effects?” he said.

Dr. Ruderman said a Cochran Review published in 2009 looking at the effects of prednisone use in RA concluded that the risk of harm needed to be considered, especially the risk of fractures and infections. Even a low-level risk could be meaningful and important.

Among those risks are a higher rate of hospitalization for infections and higher rates of cardiovascular disease and cardiovascular mortality, he said.