Treatment Tapering and Withdrawal Feasible Following Remission in Patients With Rheumatoid Arthritis

Clasped hands of an elderly lady resting on a table alongside a variety of scattered medication tablets capsule and pills prescribed for her health and as diet.
In the Rheumatoid Arthritis in Ongoing Remission (RETRO) study, researchers studied the effect of tapering and withdrawal of DMARDs in patients with rheumatoid arthritis in stable remission.

Treatment tapering and withdrawal are feasible in patients with rheumatoid arthritis (RA) in stable remission, according to study results published in The Lancet Rheumatology.

With the available treatment options, approximately 50% of patients with RA achieve stable remission; however, controlled strategies are needed during management of this population. While previous observational studies have assessed the effect of tapering or withdrawal of treatment in patients in stable remission, limited data are available from randomized controlled trials.

The Rheumatoid Arthritis in Ongoing Remission (RETRO) study was aimed at determining the outcomes of tapering and withdrawal of disease-modifying antirheumatic drugs (DMARDs) in patients with RA in stable remission.

The multicenter, prospective, randomized, controlled, open-label phase 3 RETRO trial ( Identifier: NCT02779114) included adults with RA with at least 12 months of sustained remission, defined according to Disease Activity Score using 28 joints with erythrocyte sedimentation rate (DAS28-ESR) score of less than 2.6 units.

The study sample included 303 patients with RA in remission randomly assigned to continue 100% dose DMARD (continue group; n=100), taper to 50% dose DMARDs (taper group; n=102), or taper to 50% dose DMARD for 6 months before withdrawing the DMARDs (stop group; n=101).

The primary outcome was the percentage of patients in sustained remission, based on DAS28-ESR, without relapse at 12 months.

At 12 months, remission was maintained by 81.2% of patients in the continue group, 58.6% in the taper group, and 43.3% in the stop group (P =.0005). Compared with patients who continued 100% DMARD treatment, tapering DMARD dose was associated with a 3-fold increased risk for relapse (hazard ratio [HR], 3.02; 95% CI, 1.69-5.40; P =.0003) and treatment withdrawal was associated with more than a 4-fold increased risk for disease relapse (HR, 4.34; 95% CI, 2.48-7.60; P <.0001). The majority of these patients regained remission after reintroduction of 100% dose DMARDs.

During the 12 month study period, 38 serious adverse events were reported in 29 patients, including in 10 patients (11%) in the continue group, 7 patients (8%) in the taper group, and 13 patients (14%) in the stop group. However, none of these events were related to the study treatment or led to study withdrawal.

The study had several limitations, including inability to fully exclude underestimation of disease activity in the study groups and absence of radiographic data.

“The data show that despite increased disease relapses, a considerable proportion of patients with [RA] benefit from this flexible regimen, as they stay in remission despite tapering or even stopping DMARDs. These results might prevent overtreatment in a substantial number of patients with [RA],” the researchers concluded.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Tascilar K, Hagen M, Kleyer A, et al. Treatment tapering and stopping in patients with rheumatoid arthritis in stable remission (RETRO): a multicentre, randomised, controlled, open-label, phase 3 trial. Lancet Rheumatol. Published online October 1, 2021. doi:10.1016/S2665-9913(21)00220-4