Tapering study ‘an important missing link’

3 minute read

A big new study shows some RA patients will benefit from csDMARD tapering and withdrawal, but it’s not yet clear which ones.

A three-year study looking at tapering and withdrawal from conventional synthetic DMARDs in rheumatoid arthritis patients in stable remission has reported an increased risk of flares.

While most patients in the ARCTIC REWIND study regained remission after a flare, some experienced increased radiographic joint progression, and some required more medication than at their starting point.

However, there was a subgroup of patients for whom drug-free remission was achievable. 

“The findings could assist shared treatment decisions between clinicians and the growing group of patients with rheumatoid arthritis in remission,” wrote the authors in the Lancet Rheumatology.

“Due to significant 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.”

The study included 160 RA patients taking only csDMARDs who were in a one-year sustained remission. They were randomised 2:1:1 to continue their current treatment for three years, to halve the dose of treatment for three years or halve the dosage for one year then discontinue medication for two further years.

The primary endpoint was flare-free survival over the three years.

Of the patients in the stable dose group, 80% remained flare-free, compared with 57% of the half-dose group and 38% of the half-dose tapering to withdrawal group. When compared with the stable-dose group, the risk of flare corresponded to a hazard ratio of 2.9 in the half-dose group and 4.2 in the tapering to withdrawal group.

Patients in the tapering groups who experienced flares were returned to their original treatment regimen, while those in the stable-dose group were treated according to standard of care.

At the end of three years, despite flares, most patients were in remission: 96% of the stable-dose group, 94% of the half-dose group and 91% of the tapering to withdrawal group.

“Two conventional synthetic DMARD tapering strategies were associated with significantly lower rates of flare-free survival compared with stable conventional synthetic DMARD treatment, and the data do not support non-inferiority,” concluded the authors.

“However, drug-free remission was achievable for a significant subgroup of patients.”

The ARCTIC REWIND study is one of only a few studies looking at tapering strategies in patients using only csDMARDS.

In a linked comment, Dr Elise van Mulligen of Leiden University Medical Center in the Netherlands observed that the study showed higher rates of sustained DMARD-free remission in patients tapering csDMARDs compared with other studies that focused on biological DMARDs.

“This study adds an important missing link to the contemporary literature concerning tapering of conventional synthetic DMARDs and sustained DMARD-free remission in patient with rheumatoid arthritis,” wrote Dr van Mulligen.

She suggested this could come down to severity of disease: patients with milder disease have the highest chance of sustained DMARD-free remission, and patients on biological DMARDS are likely to have more severe disease.

Nevertheless, she reiterated the study authors’ acknowledgement that the risk-benefit analysis of csDMARD discontinuation is complex.

“Although 38% of patients could reach sustained DMARD-free remission, other patients need more intensive treatment and had more radiographic joint damage progression,” wrote Dr van Mulligen.

“In the future, reducing the risk of flare should be warranted in tapering studies. An option for this aim is providing proper risk stratification beforehand, for example by using anticitrullinated protein antibody-status.”

To this end, the study authors pointed to a need for further research “to identify prognostics factors for successful tapering and identify patients not suitable for tapering conventional synthetic DMARDs, with an aim of personalised medicine in the growing group of patients with rheumatoid arthritis in remission”.

Lancet Rheumatology 2024, online 4 April

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