Persistent Burden in Early RA Despite Disease Control: insights from CareRA Trials Save

Advances in the treatment of rheumatoid arthritis (RA), particularly the treat-to-target strategy and the introduction of effective disease-modifying antirheumatic drugs (DMARDs), have improved the management of inflammation in RA. However, improved inflammatory markers do not always translate into a resolution of patients’ symptoms or improvements in functional capacity. A recent pooled analysis from the CareRA and CareRA2020 randomized controlled trials, presented at EULAR 2025, shed new light on this dissociation between biological disease control and patient-reported outcomes.

The study (Abstract: OP0330) aimed to explore how inflammatory disease activity and patient-reported disease impact evolve over time in early RA and identify predictors of persistent impact despite clinical improvements. Researchers analysed data from 608 patients with early RA who were treated using treat-to-target protocols. All patients received methotrexate and glucocorticoids as first-line therapy, with additional DMARDs introduced in those with inadequate response. Over a two-year follow-up period, data were collected on a range of measures, including a reweighted two-component DAS28 score (2C-DAS28), Health Assessment Questionnaire, and visual analogue scales (VAS) for pain and fatigue.

Using growth mixture modelling, four distinct patient trajectories were identified based on their patterns of disease activity and reported impact. Importantly, all groups showed substantial improvement in objective markers of inflammation (as captured by 2C-DAS28) but diverged considerably in their patient-reported outcomes. The largest group (38%) showed only partial improvement in symptoms, and a substantial proportion (34%) experienced “persistent impact”. This trajectory was more likely with higher baseline tender joint count and longer symptom duration (treatment delay). In the case of female sex, RF/ACPA-seropositivity or the presence of comorbidities were important in determining a persistent impact trajectory. In contrast, higher baseline swollen joint counts and inflammatory markers such as CRP were associated with more favourable trajectories. These findings highlight a subset of patients in whom the inflammatory burden appears to be less prominent, but who nonetheless report significant functional impairment and symptom burden.

A particularly important finding was that nearly one-third of patients in the “persistent impact” group escalated to biologic or targeted synthetic DMARDs by week 104, more than double the rate in groups with better patient-reported outcomes. This suggests a potential risk of overtreatment in cases where persistent symptoms may not be driven by active inflammation, raising critical questions about how best to tailor treatment in such patients.

In summary, while modern RA therapies are highly effective in controlling inflammation, this study underscores the importance of differentiating between inflammatory and non-inflammatory contributors to disease impact. Future strategies must better integrate patient-reported outcomes into clinical decision-making to avoid unnecessary treatment escalation and to provide more holistic care for those living with RA.

Abstract OP0330: ONE-IN-THREE PATIENTS WITH EARLY RHEUMATOID ARTHRITIS EXPERIENCE PERSISTENT DISEASE IMPACT DESPITE CONTROL OF INFLAMMATION: A LONGITUDINAL TRAJECTORY ANALYSIS OF TWO RANDOMIZED CONTROLLED TRIALS.