Tapering inferior to stable dose DMARDs for flare prevention in RA remission
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Tapering conventional synthetic DMARDs to a half-dose was inferior to stable-dose regimens for preventing flares during a 1-year period among patients in rheumatoid arthritis remission, according to data published in JAMA.
“Although [conventional synthetic DMARD (csDMARD)] therapy is commonly prescribed, the optimal method of dose reduction and withdrawal of csDMARD in RA is unclear,” Siri Lillegraven, MD, PhD, MPH, of Diakonhjemmet Hospital, in Oslo, Norway, and colleagues wrote. “One clinical trial that randomized patients in RA remission to either continued or discontinued csDMARD therapy showed increased rates of RA exacerbations in patients who stopped taking csDMARDs.”
“Observational data showed that tapering or discontinuing csDMARDs was associated with increased flare rates and that rapid reintroduction of therapy was associated with increased probability of regaining remission after flares,” they added. “Studies that tapered biologic DMARDs and combinations of csDMARDs and biologic DMARDs showed that these strategies might be appropriate in patients with sustained levels of very low disease activity, but it is unknown whether these data apply to patients who have attained remission with csDMARDs alone.”
To analyze the impact of tapering conventional synthetic DMARDs to a half-dose on the risk for flares, compared with those on a stable regimen, among patients in sustained RA remission, Lillegraven and colleagues conducted ARCTIC REWIND, a multicenter, randomized, parallel, open-label noninferiority study. The recruited 160 participants who had been in RA remission for 12 months, and were receiving stable conventional synthetic DMARD therapy, from 10 Norwegian hospital-based rheumatology centers.
Investigators randomly assigned participants 1:1 to either taper their therapy to a half dose or remain with a stable dose. The primary outcome was the proportion of patients with a disease flare between baseline and the 1-year follow-up. Researchers defined disease flare as a combination of a Disease Activity Score (DAS) greater than 1.6, an increase of 0.6 united or more in DAS, and at least 2 swollen joints, or if both the patient and researcher agreed that a clinically significant flare had occurred. The margin for noninferiority was set at a risk difference of 20%.
Among the participants, 156 received the allocated therapy, of whom 155 — 77 in the half-dose group and 78 in the stable-dose cohort — completed the study without any protocol violations, and thus included in the final analysis.
According to the researchers, flare occurred in 25% of those in the half-dose group, compared with 6% in the stable-dose group (risk difference = 18%; 95% CI, 7-29). Further, adverse events occurred in 44% of half-dose participants, compared with 54% in the stable-dose group. No patients discontinued due to adverse events, and no deaths occurred.
“Current treatment recommendations suggest to consider tapering of csDMARD in patients with RA who are in persistent remission with csDMARD treatment,” Lillegraven and colleagues wrote. “However, the recommendations are based on a relatively low grade of evidence. More research on this topic would be useful to address areas of uncertainty, eg, if it is possible to identify which patients can successfully taper treatment.
“Among patients with RA in remission taking csDMARD therapy, treatment with half-dose vs. stable-dose csDMARDs did not demonstrate noninferiority for the percentage of patients with disease flares over 12 months, and there were significantly fewer flares in the stable-dose group,” they added. “These findings do not support treatment with half-dose therapy.”
Perspective
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David A. McLain, MD, MACR, FACP, FRCP
Rheumatologists are often asked by patients that are doing well with rheumatoid arthritis if they can taper or stop their medications. Sometimes, as the clinician, we wonder ourselves if a patient in remission “really needs” their RA medication. This study looked at this question with a half dose taper vs. full dose conventional synthetic DMARDs in patients in remission.
The csDMARDs included methotrexate, sulfasalazine and hydroxychloroquine, tracking visits every 4 months. The results of this study show that tapering to half dose of a csDMARD resulted in a 25% flare rate compared to a 6% flare rate in the full-dose group.
This was a small study of 160 patients and the authors have called for a larger study; the results, however, demonstrate that for patients in remission, “don’t rock the boat”.
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