Reducing DMARDs in patients in stable remission is feasible with close monitoring, a trial shows, but an Australian expert says several questions need to be addressed before tapering or dose-reduction strategies become routine in clinical practice.
The Rheumatoid Arthritis in Ongoing Remission (RETRO) study assessed the effect of tapering and stopping treatment with DMARDs in rheumatoid arthritis patients in stable remission.
The German randomised, controlled Phase III trial involved patients aged at least 18 years with rheumatoid arthritis for at least 12 months before randomisation. Eligible patients were randomly assigned, regardless of baseline treatment, to either continue 100% dose DMARD (continue group), taper to 50% dose DMARD (taper group), or 50% dose DMARD for 6 months before stopping DMARDs (stop group). Patients were then assessed every 3 months and screened for disease activity and relapse.
The data, published in The Lancet Rheumatology, show that remission was maintained after 12 months in more than half of patients in the taper group (59% of 93), compared to 81% in the continue group (n=93) and 43% (n=96) in the stop group.
In comparison with the continue group, stopping treatment and tapering treatment was linked with a respective 4.34 times and 3.02 times higher risk of disease relapse. However, the majority of patients who relapsed regained remission after taking their normal DMARDs dose again.
On the safety side, serious adverse events occurred in ten of 93 (11%) patients in the continue group, seven of 93 (8%) patients in the taper group, and 13 of 96 (14%) patients in the stop group, though none were considered to be related to the intervention.
The researchers, led by rheumatologist Dr Koray Tascilar, at the Universitätsklinikum Erlangen, concluded that decreasing use of antirheumatic drugs in patients with rheumatoid arthritis in stable remission is feasible, but would require “tight monitoring of disease activity” given the higher relapse rates observed in those with tapered doses in the study.
Questions remain
While there have been previous studies investigating dosing reduction in patients with rheumatic conditions, RETRO is particularly important as the baseline treatment of patients taking part in the trial “reflected combinations of conventional synthetic DMARDs and biological DMARDs seen in clinical practice,” noted Professor Catherine Hill, from the Faculty of Health and Medical Sciences at the University of Adelaide in a related comment.
The study also used a simple, pragmatic one-size-fits-all treatment-tapering strategy, she noted.
“The RETRO trial therefore represents a randomised controlled trial that emulates a real-life setting, with results directly relevant to clinical practice,” she wrote.
Nevertheless, while the findings indicate that treatment tapering or discontinuation is “a feasible goal for many real-world patients” who are in stable remission, “further refinements are needed” and there are “many questions that relate to a risk-benefit analysis of treatment discontinuation, and how success should be evaluated,” said Professor Hill.
Talking to the limbic, Professor Chris Edwards, Honorary Consultant Rheumatologist at University Hospital Southampton NHS Foundation Trust, who wasn’t involved in the trial, said RETRO is “a really interesting study” but also agreed that significant questions still need to be addressed before tapering or dose-reduction strategies become routine in UK clinical practice.
“There are a number of studies that have addressed dosing reduction and medicines optimisation strategies which have shown broadly similar findings that you can dose reduce in many people. But the questions that remain are, can you pick the people in whom you can dose reduce successfully, and if you can’t do that, do you have the resources to be able to see people frequently enough to allow their flare to be picked up prior to them doing any damage, whether that’s physical of psychological?”
Along similar lines, Hill concluded that “contemplation of treatment tapering or discontinuation in some patients with rheumatoid arthritis is remarkable and a measure of how far treatments have advanced. However, further work to address outstanding questions on who should taper and how best to do it is still required.”