Reducing doses of biologic or targeted synthetic disease-modifying antirheumatic drugs was noninferior to continuing standard treatment over 24 weeks in patients with rheumatoid arthritis (RA) and sustained disease control.
In the multicenter, open-label RESTORE-RA noninferiority trial, investigators enrolled 348 patients with RA across 12 tertiary rheumatology centers in South Korea between July 2020 and December 2024. Eligible patients were aged 19 to 74 years and had maintained low disease activity (LDA) for at least 6 months while receiving stable doses of biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). Patients were randomly assigned to continue standard dosing (n = 177) or undergo structured tapering (n = 171). Tapering involved extending dosing intervals for injectable biologics in 2 steps or reducing oral Janus kinase (JAK) inhibitor doses by approximately 50%, with treatment reescalation permitted if disease activity worsened.
The primary outcome was maintenance of LDA at week 24, defined as a Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) of 3.2 or lower. Secondary outcomes included remission rates, changes in disease activity measures, patient-reported outcomes, quality of life, and adverse events. Noninferiority was assessed using a prespecified margin of 10 percentage points.
At week 24, 149 of 169 patients (88.2%) in the tapering group maintained LDA compared with 155 of 173 (89.6%) in the continuation group in the per-protocol analysis. The results met the prespecified criterion for noninferiority. Findings were consistent in the full analysis set, in which LDA maintenance rates were 88.1% with tapering and 89.7% with continued treatment.
Although the primary outcome was comparable between groups, some secondary disease activity measures favored continued treatment. At week 12, remission based on DAS28 using C-reactive protein was achieved by 86.4% of patients undergoing tapering compared with 94.9% receiving continued treatment. At week 24, remission rates were comparable, although DAS28-ESR and Simplified Disease Activity Index scores remained higher in the tapering group. Patient-reported disease activity and quality-of-life measures did not differ significantly between groups.
Treatment reescalation helped restore LDA in most patients who lost disease control after tapering. Among 23 patients in the tapering group who lost LDA by week 12, 17 regained LDA by week 24 following protocol-guided treatment reescalation. However, 14 additional patients who maintained LDA at week 12 subsequently lost disease control by the final assessment.
Exploratory subgroup analyses suggested that responses to tapering differed across drug classes. Among patients receiving tumor necrosis factor (TNF) inhibitors, LDA was maintained in 94.5% of those undergoing tapering compared with 87.7% receiving continued treatment. In contrast, among patients receiving oral JAK inhibitors, maintenance rates were 80.3% with tapering compared with 92.2% with continued treatment. Within the tapering group, JAK inhibitor use was associated with lower odds of maintaining LDA at week 24 compared with TNF inhibitor use. These exploratory analyses were not powered to establish noninferiority within individual drug classes.
Adverse events were uncommon during the 24-week follow-up, with 25 reported overall:16 in the tapering group and 9 in the continuation group. One serious infection and 1 malignancy occurred in the tapering group, whereas neither was reported in the continuation group. No new safety signals related to dose tapering were identified.
The authors acknowledged several limitations, including the 24-week follow-up period, which was insufficient to assess long-term disease control, radiographic progression, or cumulative safety outcomes. The open-label design introduced potential performance and assessment bias, while differences in tapering schedules across drug classes made it difficult to determine whether treatment-specific responses reflected drug mechanism or the tapering strategy itself. Additionally, the trial enrolled 348 patients compared with the originally planned 446, and recruitment exclusively from South Korean centers may limit generalizability to other populations and health care settings. Using LDA maintenance as the primary outcome may also have been less sensitive than flare-based measures in detecting mild or transient worsening of disease activity.
“With careful patient selection, close monitoring, and timely treatment reescalation when needed, dose tapering may reduce treatment burden while maintaining disease control and health-related quality of life,” wrote lead study author Dong-Jin Park, PhD, of Chonnam National University Medical School and Hospital in Gwangju, South Korea, and colleagues, in the study's conclusion.
Despite the overall finding of noninferiority, the authors cautioned that tapering efficacy may vary by drug class and mechanism of action, underscoring the need for longer-term, drug-specific studies.
The study was supported by the Patient-Centered Clinical Research Coordinating Center, funded by the Ministry of Health & Welfare, Republic of Korea. Disclosures are available on the journal website.
Source: Arthritis & Rheumatology
