Rheumatoid arthritis
and APLAR emphasise sustained remission as a key therapeutic objective, requiring continuous control of inflammation to prevent structural damage and opti- mise long-term outcomes. 11–13 However, both in clinical studies and real-world practice, relapse of RA remains a common challenge. 14 15 The findings indicate that drug tapering is a risk factor for relapse in univariable analysis and is confirmed as an independent risk factor in multivariable anal- ysis. Further analysis of the interaction between CliDR status and tapering reveals that drug tapering is associ- ated with an increased risk of relapse in the non-CliDR group compared to the CliDR group. This suggests that tapering may be relatively safe in CliDR patients, whereas in non-CliDR patients it exposes an already unstable immunologic milieu, resulting in disproportionately higher relapse rates. In previous studies, sustained remission rates are not satisfactory, especially when tapering the DMARDs. 16–18 A systematic review reported that four studies on synthetic DMARD showed flare rates ranging from 8% at 24 weeks to 63% at 4 months after de-escalation, 15 studies on tumour necrosis factor blockers reported estimated flare rates of 0.26 (95% CI 0.17 to 0.39) and 0.49 (95% CI 0.27 to 0.73) for good-quality and moderate-quality studies respectively by meta-analysis, three studies on tocilizumab demonstrated flare rates of 41% after 6 months, 55% at 1 year and 87% at 1 year and three studies on abatacept de-escalation presented flare rates of 34% at 1 year, 41% at 1 year and 72% at 6 months. 19 Enhancing sustained remission in RA may be achiev- able through full suppression of residual inflamma- tion and individualised risk-stratified management for patients prone to disease flares. 20 Inflammatory markers, including CRP and ESR, are used to evaluate systemic inflammation, while joint tenderness and swelling assess local inflammation. CliDR, which requires normal systemic inflammatory markers and zero local inflamma- tion, shows that strict inflammation control is beneficial for achieving long-term clinical remission. Previous studies have also suggested that deep remis- sion contributes to the maintenance of remission in RA. In a randomised controlled trial (RCT), studies have suggested that patients achieving deep remission (DAS28 ≤ 1.98) have a higher probability of remaining in remission when tapering biologics. 21 22 In a different study, the ARCTIC study’s more rigorous treatment target (DAS44<1.6 plus 0 of 44 swollen joint count) resulted in more patients achieving ACR/EULAR Boolean remis- sion during follow-up than in the Norwegian Very Early Arthritis Clinic (NOR‑VEAC) study (DAS28<2.6). 22 This view is also supported by the PREDICTRA (ImPact of Residual Inflammation Detected via Imaging TEch- niques, Drug Levels and Patient Characteristics on the Outcome of Dose TaperIng of Adalimumab in Clinical Remission Rheumatoid ArThritis (RA) Patients) data, as 64% of patients with established RA (mean disease duration of 12.9 years) who were in deep, long remission
(mean DAS28(ESR) of 1.7) for a mean of 5.4 years did not experience a flare after bDMARD tapering. 23 The HONOR (Humira discontinuation without func- tional and radiographic damage progressioN follOwing sustained Remission) study identified DAS28(ESR) ≤ 2.16 as a critical cut-off point for predicting flare; 78% of patients with mean DAS28(ESR) ≤ 2.16 at the time of adali- mumab withdrawal maintained remission after 6 months (vs 2% for DAS28(ESR)>2.16, <2.6). 24 In comparison with these studies, aiming for a stricter remission defini- tion may further enhance the potential benefits of a T2T strategy. The concept of ‘imaging remission’—defined as the absence of power-Doppler signal or MRI osteitis—has been proposed as an ultimate treatment goal. However, recent randomised trials found that imaging-guided tapering did not significantly reduce relapse rates beyond what was achieved with stringent clinical remission criteria alone. 25 26 Given technical and resource constraints asso- ciated with routine imaging, CliDR represents a more accessible and clinically actionable target for widespread use. Although patients achieving CliDR experience lower relapse rates during dose tapering, determining ‘when to reduce’ and ‘whether to stop’ therapy remains a crit- ical unmet need for individualised care. Recent evidence indicates that deep-learning imaging combined with multi-omics integration can accurately forecast disease activity and drug response, enabling data-driven, patient- specific decisions on tapering or withdrawal and shifting RA management from a one-size-fits-all approach to precision-based stratification. 27 This study has several limitations, including: (1) poten- tial selection bias from single-centre enrolment, which may restrict generalisability to broader populations due to institutional-specific treatment protocols and patient demographics; (2) restricted sample size reducing power to detect inter-group differences, although the sample size (n=145) provided adequate power (>85%) to detect moderate effect sizes (HR ≥ 1.8), it was underpowered (62%) to identify small-to-moderate effects (HR=1.5), potentially missing clinically relevant but statistically marginal differences; (3) third, because fewer than 10% of participants received bDMARDs, we could not eval- uate whether CliDR also predicts successful biologic tapering; dedicated studies or larger registries enriched with bDMARD-treated patients are required to address this question; (4) finally, as 97% of our cohort were ACPA-positive, we were unable to assess the influence of serostatus on outcomes. Future multicentre studies with broader serological representation and randomised trials are needed to confirm the generalisability of our findings. Furthermore, integrating PROs into the defini- tion of CliDR constitutes an important avenue for future research, as it may capture a distinct dimension of disease burden. In conclusion, our study demonstrates that achieving CliDR is a strong predictor of sustained remission and
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Li H, et al . RMD Open 2026; 12 :e006387. doi:10.1136/rmdopen-2025-006387
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