Patients with rheumatoid arthritis (RA) in remission who tapered and then fully stopped either conventional synthetic disease-modifying antirheumatic drug (csDMARD) or tumor necrosis factor (TNF)–inhibitor therapy experienced more disease flares than those who received stable dose treatment in an open-label, randomized trial.
In the 3-year trial, called ARCTIC REWIND, 80% of patients taking stable doses of only csMARDs remained flare-free compared with 38% in another treatment arm taking only csDMARDs who tapered to a half dose and then discontinued all after 1 year. In patients who continued to receive half-dose csDMARDs for the entire study period, 57% remained flare-free.
University of Nebraska Medical Center
Dr. James O'Dell
A separate two treatment arms of the study that assessed the effect of tapering TNF-inhibitor treatment to withdrawal showed that only 25% of patients who tapered TNF inhibitor to withdrawal remained flare-free over 3 years compared with 85% who remained on a stable TNF-inhibitor dose.
Though the risk for flare was higher in both the half-dose csDMARD and drug-free groups, the results also suggested that tapering medication “could be a realistic option for some patients with rheumatoid arthritis in sustained remission on csDMARDs,” wrote Kaja Kjørholt, MD, of the Center for Treatment of Rheumatic and Musculoskeletal Diseases at Diakonhjemmet Hospital in Oslo, Norway, and colleagues.
The 3-year results for the csDMARD-only arms of the trial were published in The Lancet Rheumatology. The 3-year results of the TNF-inhibitor arms of the study were presented as an abstract at the annual meeting of the American College of Rheumatology (ACR).
Don’t Avoid Tapering But Take an Individualized Approach
Many rheumatologists will taper patients with RA in remission to lower doses of medication, but the protocols for this study do not reflect clinical practice, noted James R. O’Dell, MD, chief of the Division of Rheumatology at the University of Nebraska Medical Center in Omaha, Nebraska. He was not involved with the research.
“I don’t know of any rheumatologist who would ever think that it was a good idea to taper somebody completely off of all DMARDs,” he told this news organization. “The only surprise is that more of them didn’t flare,” he continued, though he suspected that more patients would flare if they were followed for more time. Rheumatologists also would take a much more individualized approach when tapering to lower doses, he added, and do so at a much slower rate than what was observed in this study.
Both the ACR and the European Alliance of Associations for Rheumatology recommendations for the management of RA stated that tapering DMARDs can be considered for patients who have sustained remission, but they do not mention discontinuing medication entirely.
In the TNF-inhibitor arms of the trial, the tapering group received a half dose of a TNF inhibitor for 4 months before stopping therapy entirely, which Dr. O’Dell noted was a large dip in too short a period.
“Nobody should be surprised that these people flared a lot,” he said. However, tapering to lower doses of a TNF inhibitor can be successful, he noted, adding that more than half of his patients taking a TNF inhibitor are on less than their original dose. Completely tapering off a TNF inhibitor is less common and depends on what other DMARDs a patient is taking, he said, and complete drug-free remission in this population is highly unlikely.
Dr. O’Dell emphasized that the takeaway from these results should not be to avoid tapering medication because of flare risk but instead a tailored approach — something that is not possible with a study protocol — is needed.
“We want our patients to have all the medicine they need and no more,” he said. “That sweet spot is different for each individual patient for how much TNF inhibition or how much conventional therapy they need. If we’re thoughtful about that in the clinic, we can find that sweet spot,” he said.