Tapering or withdrawal of antirheumatic drugs in patients with rheumatoid arthritis (RA) in stable remission may be feasible, with maintenance of remission occurring in half of patients, according to study results published in Lancet Rheumatology.

Rheumatoid arthritis often requires long-term treatment with disease-modifying antirheumatic drugs (DMARDs). Strategies that include structured tapering of DMARDs and cessation of medications after successful tapering should be considered in the management of patients with RA in remission. 

Researchers conducted a prospective randomized controlled trial (Reduction of Therapy in RA Patients in Ongoing Remission [RETRO]; ClinicalTrials.gov Identifier: NCT02779114) to study DMARD maintenance, tapering, and discontinuation in patients with RA in stable remission.


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Adult patients with RA for at least 12 months whose disease was stable after receiving treatment for at least 6 months with at least 1 conventional synthetic DMARD (including methotrexate, leflunomide, sulfasalazine, azathioprine, or hydroxychloroquine) or a biologic DMARD (including abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, or tocilizumab), with or without conventional synthetic DMARDs, were included in the study. Patients receiving Janus kinase inhibitors were not included; however, use of stable low-dose oral glucocorticoids (≤5 mg/day prednisolone-equivalents) was allowed. Eligible patients also had sustained Disease Activity Score using 28 joints (DAS28) with erythrocyte sedimentation rate (ESR) remission (score <2.6 units).

A total of 282 patients were randomly assigned into 3 treatment groups and observed for 12 months (n=93 continue group, n=93 taper group, and n=96 stop group). In the continue (control) group, all DMARD treatments and glucocorticoids were continued at full dose without modification. In the taper group, doses of all DMARDs and glucocorticoids were reduced by 50%. In the stop group, doses of all DMARD treatments and glucocorticoids were reduced by 50% for 6 months and then, if disease had not relapsed, all treatments, including glucocorticoids, were stopped.

Median times to relapse among patients with relapse were 30.6 weeks (IQR, 14.9-39.7 weeks) in the continue group, 24.3 weeks (IQR, 12.3-43.0 weeks) in the taper group, and 26.1 weeks (IQR, 10.1-33.0 weeks) in the stop group.

Overall, 61% (n=173) of patients remained in DAS28 remission without any relapse during the 12-month study period, whereas 39% (n=109) had relapses. Relapse rates were significantly higher in patients who were tapered off or stopped receiving DMARDs than patients who were continued receiving a 100% dose. Remission was maintained at 12 months by 81.2% (95% CI, 73.3%-90.0%) in the continue group, 58.6% (95% CI, 49.2%-70.0%) in the taper group, and 43.3% (95% CI, 34.6%-55.5%) in the stop group (P =.0005). 

Women with RA, patients with a longer duration of disease, the presence of rheumatoid factor, anticitrullinated protein antibody (ACPA)-positive RA, or both, baseline treatment with biologics, and higher baseline DAS28 scores, were more likely to have a relapse after tapering or withdrawal of treatment.

At least 85% of the patients in each group were either in remission or had low disease-activity status at all visits. Most of these patients regained remission after reintroducing the DMARDs. The overall risk for remission loss after reduction or cessation of treatment vs continuation was similar between groups.

During the study period, there were 38 serious adverse events among 29 study participants, including 1 death due to probable myocardial infarction in the continue group. None of the serious adverse events were considered to be related to study treatment or led to withdrawal from the study.

Although the study was a randomized controlled trial, patients and assessors were not blinded from treatment; placebo substitution was not feasible; and that radiographic data were missing, making it difficult to identify radiographic progression in the reduction arms.

“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,” the researchers concluded.

Disclosure: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.

Reference

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. 2021;3:e767-777. doi: 10.1016/ S2665-9913(21)00220-4