TOPLINE:

In patients with rheumatoid arthritis (RA) in remission, reducing doses of biologic disease-modifying antirheumatic drugs (DMARDs) was not noninferior to standard treatment in preventing disease flares at 1 year but had a similar safety profile. Prediction models performed well, and adding data on molecular markers improved their accuracy for flare risk and sustained remission.

METHODOLOGY:

• Researchers conducted a phase 4, open-label, noninferiority trial across five Spanish hospitals to compare flare rates with standard-dose vs dose-reduced biologic DMARDs in adults with RA in sustained remission and to identify predictors of flare and sustained remission.
• They included 195 adults with RA in sustained remission who were on stable biologic DMARDs for at least 6 months (mean age, 63 years; 83% female). Remission was defined as one of the following: having a Disease Activity Score in 28 joints (DAS28) ≤ 2.6, having a Simplified Disease Activity Index (SDAI) score ≤ 3.3, or meeting the American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) Boolean remission criteria.
• Patients were randomly assigned to either continue standard dosing (n = 99) or taper biologic therapy (n = 96) by reducing the dose or extending dosing intervals. Stable conventional DMARDs and oral steroids up to 10 mg/d were allowed.
• The primary outcome was the joint flare rate at 12 months, defined as the simultaneous loss of DAS28-, SDAI-, and ACR/EULAR Boolean-based remission. Researchers used a 10% noninferiority margin to test whether tapering was no more than 10 percentage points worse than standard dosing.
• Two prespecified clinical prediction models were developed — one for joint flares and one for sustained remission — using baseline clinical variables. Additional exploratory analyses incorporated data on molecular biomarkers to assess whether the model’s predictive accuracy improved.

TAKEAWAY:

• At 12 months, joint flares occurred in 22.7% vs 17.2% of patients in the dose reduction group vs the standard dose group. The risk difference was -5.5% (95% CI, -16.8% to 5.7%; P = .33), and the prespecified noninferiority margin was not met because the lower limit of the 95% CI exceeded the noninferiority margin of -10%.
• Flare-free survival was significantly lower with dose reduction at 18 and 24 months (P < .05 for both).
• The clinical flare prediction model performed well (area under the curve [AUC], 0.84), and its discriminative ability improved with the addition of molecular biomarker data (AUC, 0.91). The sustained remission model achieved an AUC of 0.77, which improved to 0.88 with the addition of molecular data.
• Adverse events did not differ significantly between groups.

IN PRACTICE:

“The development of accurate clinical and molecular models to predict both flare risk and sustained remission represents an important step toward precision medicine in RA. These tools may guide personalized treatment decisions, allowing safe implementation of tapering strategies in appropriately selected patients,” the authors of the study wrote.

SOURCE:

The study was led by Francisco J. Blanco, MD, PhD, Complexo Hospitalario Universitario de A Coruña in A Coruña, Spain. It was published online on January 29, 2026, in Rheumatology.

LIMITATIONS:

The study was open label, which may have introduced performance or expectation bias despite blinded disease activity assessments. Researchers did not include imaging; thus, they may have missed subclinical inflammation before flares. They used 1987 ACR criteria, which may have underrepresented early or seronegative disease.

DISCLOSURES:

The study received funding from Instituto de Salud Carlos III through multiple projects co-funded by the European Regional Development Fund and European Union-NextGenerationEU. Additional funding was provided by a grant from Xunta de Galicia. One PhD student reported receiving support from Cátedra FSR-UDC, Universidade da Coruña. Several authors reported receiving grants, speaker fees, contracts, and support for attending meetings and having other financial ties with multiple pharmaceutical and healthcare companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.