The impact of patients reported flares on functional impairment in rheumatoid arthritis patients with low-disease activity: A prospective cohort study based on the AMBRA trial

Background: Flares - episodes of worsening in disease activity - are common features in patients with rheumatoid arthritis (RA), even in remission or in low disease activity state. There are different definitions of flare. It is unknown whether patient reported flares lead to suboptimal long-term outcomes. Objectives: To investigate whether transient patient reported flares can influence functional disability in patients with established low active RA. Methods: Out of 287 patients from the AMBRA trial (1), 268 RA patients with low disease activity (DAS28CRP MCID of 0.22) was compared across three groups and the association between flare phenotype and functional outcome was analyzed by logistic regression. Results: 70% were female, median age [IQR] was 63 years [55;70], 73% were rheumatoid factor positive, 71% anti-CCP positive and all had established RA (median [IQR] 7 years [4;13]). Based on the flare questionnaire three groups were distinguished: No-flares group (n=77), transient flares group (n=141) and patients with persistent joint complaints (n=50). Worsening in functional capacity (HAQ>0.22) was seen in 13%, 21% and 40% of patients with no flares, with transient flares and those with persistent joint complaints, respectively (p=0.0015). Compared to the reference group (no flares) worsening in functional capacity was potentially related to "flare phenotype": OR 1.81 (95%CI: 0.83-3.94, p=0.134) for the transient flare status, and statistically significantly associated with persistent joint complaints OR 2.01 (1.22-3.31, p=0.006). Conclusions: RA patients with established low disease activity, who self-report persistent joint complaints have worse functional outcome compared to patients with transient flares and without flares.