Tapering csDMARDs in RA remission fails to achieve non-inferiority vs. stable dose
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Key takeaways:
- Tapering regimens were linked to significantly higher flare risk among patients in RA remission.
- The results highlight the “complex” risk-benefit analysis of tapering.
Patients in rheumatoid arthritis remission who tapered off conventional synthetic disease-modifying antirheumatic drugs had higher risks for flares, with two methods failing to reach non-inferiority vs. stable dosage, according to data.
“An increasing number of patients with rheumatoid arthritis achieve sustained remission, even when using first-line treatment with methotrexate and other conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs),” Kaja E. Kjørholt, MD, of Diakonhjemmet Hospital, in Norway, told Healio regarding the study published in The Lancet Rheumatology.
“Tapering towards drug-free remission could be an attractive treatment goal among these patients due to potential reductions in adverse events, burden of taking medication, and health care cost,” she added. “However, evidence regarding effects of tapering or withdrawal of csDMARDs among patients with RA in remission using csDMARD treatment only were sparse before this study was designed.”
To weigh tapering methods against stable treatment in patients in RA remission, Kjørholt and colleagues conducted the 3-year, open-label, randomized controlled non-inferiority ARCTIC REWIND trial. Across 10 hospitals in Norway, adults in sustained remission from RA were randomly assigned in a 2:1:1 ratio to receive either a stable dose of csDMARDs (n = 80), a half dose (n = 42) or a half dose for a year, followed by 2 years of complete withdrawal (n = 38). Among the 156 patients who ultimately underwent their treatment strategy, the mean age was 55.3 years.
Patients completed follow-up visits every 4 months. At the baseline visit, both tapering groups reduced their csDMARD dose by half. The primary endpoint was disease flare over 3 years, analyzed in terms of the difference in flare-free survival and risk in the per-protocol population (n = 155), with a non-inferiority margin of 20%. Patients returned to their full dose if they experienced a disease flare.
Overall, the tapering groups demonstrated significantly increased risks for flares, according to the researchers. In the stable-dose group, 80% remained flare-free (95% CI, 69%-88%) vs. 57% in the half-dose group (95% CI, 41%-71%) and 38% in the group that tapered to withdrawal (95% CI, 22%-53%). The tapering groups failed to achieve non-inferiority vs. the stable dose group, with a difference in flare risk of 23% (95% CI, 6%-41%) for the half-dose group and 40% (95% CI, 22%-58%) for the taper-to-withdrawal group.
Still, tapering conventional synthetic DMARDs, and even withdrawing, “were realistic for some of the patients,” Kjørholt said, adding that the risk-benefit analysis is “complex.”
“Even though most patients regained remission after reinstatement of full-dose csDMARDs, tapering to half-dose was associated with an increased risk for joint damage, and a significant proportion of patients needed intensified DMARD treatment and use of glucocorticoids after the tapering to withdrawal attempt,” she said.
In addition, the research team was “somewhat surprised” to find that 27% of patients in the group that tapered to withdrawal used more intense DMARD treatment at the end of the study compared with the beginning of the study, Kjørholt said.
“Even though the initial csDMARD-treatment was reinstated upon flare, these patients needed to increase their csDMARD dose or add a biological DMARD to regain disease control,” she said.
“We were also a little surprised to see a significant difference in radiologic joint progression between the half-dose and the stable group, even though 57% of the patients who tapered treatment to half-dose did not flare and those who did regained remission quickly,” Kjørholt added. “On the other hand, there were surprisingly few flares in the stable group, suggesting good chances of remaining in remission as long as medication are continued.”
Perspective
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Daniel J. Wallace, MD, FACP, MACR
A group of 160 Norwegian patients with rheumatoid arthritis doing well on DMARDs were randomized to three different tapering regimens over a 3-year period. There was non-inferiority, or no real difference, among the groups in their ability to achieve or maintain long-term remission.
This emphasizes the experience of most rheumatologists that tapering regimens are best individualized based on unique clinic features and comorbidities that characterize each patient, and that there is no one approach that is more likely to induce remission. In the United States, more patients are subject to insurance restrictions and variabilities, and more patients are on biologics or small molecule therapy, which renders this treatment approach less reliable.
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Kjørholt KE, et al. Lancet Rheumatol. 2024;doi:10.1016/S2665-9913(24)00021-3.
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