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14-05-2024 | Rheumatoid Arthritis | Editor's Choice | News

Conventional synthetic DMARD tapering increases flare risk for some patients with RA

Author: Radhika Dua


medwireNews: Tapering conventional synthetic disease-modifying antirheumatic drugs (DMARDs) to half dose or withdrawal in rheumatoid arthritis (RA) patients with sustained remission is associated with an increased risk for flare compared with stable treatment, although some patients do remain flare-free with such strategies, show findings from the ARCTIC REWIND trial.

“Our data illustrate that the risk–benefit evaluation of tapering and withdrawal of conventional synthetic DMARDs is complex,” point out the researchers in The Lancet Rheumatology.

They found that over a 3-year period, 80% of patients with RA receiving a stable dose of conventional synthetic DMARDs remained flare free, compared with 57% who tapered their treatment to half the dose and 38% who tapered their treatment to withdrawal.

Commenting on the findings, Elise van Mulligen (Leiden University Medical Center, the Netherlands) notes that while flare-free survival was the primary outcome of the study, DMARD-free remission as demonstrated by the patients who tapered treatment to withdrawal is an “important" and "highly relevant” outcome, given the “paucity of recent studies on tapering conventional synthetic DMARDs.”

Quoting a range of 10–20% given in a recent systematic review, she says that the 38% rates in this study “seems to substantiate that patients that only need conventional synthetic DMARDs might be better able to reach sustained DMARD-free remission compared to those on biological DMARDs.”

The trial, conducted at 10 hospitals in Norway, involved 156 patients (mean age 55.3 years; 67% women) with RA who had been in sustained remission for at least a year on stable conventional synthetic DMARDs. The participants were randomly assigned to one of three treatment strategies: continuous stable-dose conventional synthetic DMARDs for 36 months (n=78); half-dose conventional synthetic DMARDs for 36 months (n=41); or half-dose conventional synthetic DMARDs for 12 months followed by complete withdrawal of all conventional synthetic DMARDs from 12 to 36 months (n=37).

The conventional synthetic DMARDs included monotherapy or a combination of methotrexate, sulfasalazine, hydroxychloroquine, or leflunomide.

Over the 3 years, the absolute risk for flare, defined as a combination of a Disease Activity Score (DAS) greater than 1.6 points, an increase in score of more than 0.6 points, and at least two swollen joints, was a significant 23% greater for patients adopting the half-dose treatment strategy, compared with those continuing with stable-dose treatment, and a significant 40% greater for those tapering to withdrawal. In both cases the absolute risk exceeded the 20% margin for noninferiority. The corresponding adjusted hazard ratios were a significant 2.9 and 4.2. 

Kaja Kjørholt (Diakonhjemmet Hospital, Norway) and colleagues observe that, irrespective of whether patients had a flare, DAS remission (<1.6 points) at 3 years was achieved by 96% of 67 patients in the stable-dose group, 94% of 36 patients in the half-dose group, and 91% of 34 patients in the withdrawal group.

However, the rate of radiographic joint progression, as indicated by a van der Heijde–modified Sharp score of at least 3 points, was higher in the half-dose and withdrawal groups than the stable-dose group, at 19% and 11% versus 1%, respectively, “which might support continuing stable-dose conventional synthetic DMARD treatment,” say the researchers.

And treatment had to be intensified (increasing the dose or adding a biological DMARD) in more patients in the withdrawal group than the stable dose group, at 27% versus 14%, by the end of the study.

Adverse events occurred in 83% of patients in the stable-dose group, 90% of those in the half-dose group, and 97% of those in the withdrawal group, the most frequent of which was infection. Serious adverse events occurred in a respective 17%, 10%, and 16%, and there was one death considered unrelated to study medication in the stable-dose group.

“This study provides long-term results on several aspects of importance for shared decision making between the patient and the physician in the increasingly common clinical situation of long-term remission in patients with rheumatoid arthritis,” say Kjørholt et al.

“The patient should be thoroughly informed about the advantages and disadvantages of tapering, taking the patient’s situation and preferences, burden of potential side effects, and medical history into account before deciding on treatment strategy.”

They recommend that “due to significant increased risk of flare after tapering and withdrawal, the patients should be closely monitored, and the possibilities of tight control should be considered before tapering.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group.

Lancet Rheumatol 2024; 6: E268–E278
Lancet Rheumatol 2024; 6: E254–E255


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