Remission versus low disease activity as treatment targets in rheumatoid arthritis: how to strike the right balance between too strict and too lenient targets? A meta-epidemiological study of individual patient data.

Abstract

Objectives: To evaluate the impact of using Simplified Disease Activity Index (SDAI)-LDA (low disease activity) versus different definitions of remission as a treatment target in established rheumatoid arthritis.

Methods: A meta-epidemiological study of individual patient data from eight randomised controlled trials was performed. Four definitions of the target were considered at 6 months: (1) SDAI-LDA: SDAI≤11; (2) SDAI-Remission: SDAI≤3.3; (3) 4V-Remission: Tender and swollen 28-joint counts and C reactive protein (mg/dL) all ≤1 and patient global assessment (PGA)≤2 and (4) 3-variable (3V)-Remission: as 4V, excluding PGA. The mean radiographic change in the modified total Sharp-van der Heijde score (mTSS) and the Good Radiographic Outcome rates (defined as a change of ≤0.5 units mTSS) over 2 years were compared among target definitions. Radiographic progression and the distribution of the individual criteria of the Boolean definition in the only LDA subgroup (3.3

Results: In total, 4374 patients (mean disease duration of 5.9 years (95% CI 4.6; 7.1)) were included. The pooled rate of SDAI-LDA at 6 months was 49%, with 13% in SDAI-remission. The 4V-Remission and 3V-Remission were achieved by 16% and 23%, respectively. Mean radiographic progression was 0.55 (0.14; 0.96) units for SDAI-LDA and 0.22 (-0.09; 0.54), 0.28 (-0.07; 0.62), 0.28 (-0.10; 0.65) for SDAI-Remission, 4V-Remission and 3V-Remission states, respectively. Patients with SDAI Pure-LDA presented significantly more radiographic progression than patients in SDAI-Remission (mean 0.72 vs 0.22 units, p<0.05). Over 53% of all patients achieving SDAI-LDA were not in 3V-Remission and had more mean radiographic progression over 2 years than those who met both targets (0.70 vs 0.25 units, p=0.014). Among patients with SDAI-LDA but not in SDAI-Remission, 40% scored PGA>2, reflecting relevant disease impact.

Conclusion: SDAI-LDA is associated with more structural damage over 2 years than any of the definitions of remission. It also allows substantial disease impact to go unchecked and uncontrolled. Physicians should strive for remission whenever possible and safe while also taking into account the different individual disease activity parameters included in the adopted definition.