Tapering of conventional synthetic DMARDs has been linked with increased risk of flare and, in some cases, radiographic joint progression compared to stable treatment in patients with rheumatoid arthritis, researchers report.
However, sustained drug-free remission was observed in just over two-thirds of patients who withdrew therapy after three years’ follow-up, they noted in a paper published in The Lancet Rheumatology (link here).
“Our data illustrate that the risk-benefit evaluation of tapering and withdrawal of conventional synthetic DMARDs is complex, as some patients achieve sustained drug-free remission, whereas others need intensified treatment after tapering or have radiographic joint damage progression,” the team of researchers said.
From a clinical perspective, because of the significantly increased risk of flare after tapering and withdrawal, patients should be closely monitored, “and the possibilities of tight control and patients’ own preferences should be considered before tapering,” they stressed.
The open-label, randomised controlled, non-inferiority trial ARCTIC REWIND compared outcomes associated with three different treatment regimens in patients with rheumatoid arthritis: stable conventional synthetic (cs) DMARDs (n=80); half-dose csDMARDs (n=42); and half-dose csDMARDs for one year followed by their complete withdrawal (n=38).
Patients included in the trial, from 10 hospitals in Norway, were aged 18-80 years and had sustained remission for at least one year on csDMARD therapy.
After three years of follow-up, 80% of the stable dose group were flare-free, compared to 57% of those who received a half-dose and 38% in the half-dose tapering to withdrawal study arm.
Compared to the group who received stable csDMARD treatment, there was a 23% higher risk of flare in the half-dose group (p=0·010) and a 40% higher risk in the tapering to withdrawal arm (p<0·0001).
“The risk of disease flare was significantly higher with the two tapering strategies than with stable-dose therapy, with an adjusted hazard ratio of flare 2.9 (95% CI 1.5-5.9) in the half-dose group, and 4.2 (2.2-8.2) in the half-dose tapering to withdrawal group,” according to the paper.
Notably, the analysis also revealed a statistically significant difference in joint damage between patients taking stable-dose csDMARDs and those taking half-dose csDMARDs; 19% in the latter group had radiological progression of three units or more (over three years) compared with 1% in the stable-dose group.
Most patients in all three groups had regained remission at the next visit following a flare, but at the end of the study, a significantly greater proportion in the withdrawal group than in the continued therapy group had intensified DMARD treatment (27% versus 14%, respectively).
Differences between the treatment arms were also observed in systemic glucocorticoid use: 15% in the stable-dose group, 18% in the half-dose group, and 51% of 37 patients in the half-dose tapering to withdrawal group.
“The ARCTIC REWIND trial is a really important study,” said Professor James Galloway, Professor of Rheumatology at King’s College London and an Honorary Consultant in Rheumatology at King’s College Hospital, commenting on the findings.
“Our colleagues in Norway have addressed a question that is highly relevant to routine practice in the care of patients with rheumatoid arthritis. The question is whether or not you can taper or withdraw conventional synthetic DMARD therapy in someone who has stable rheumatoid arthritis. The headline answer appears to be no, with substantially more patients flaring with either of the tapering strategies included,” he told the limbic.
“This is not say that no one should taper therapy, as clearly for some patients it is possible. However, the ARCTIC REWIND trial provides insight into the question and should help clinicians and patients make more informed treatment choices going forward”.