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  • ABA overall drug retention time was similar across all

    2018-11-14

    ABA overall drug retention time was similar across all groups (p=0·11). However, as could be expected, ABA drug retention until discontinuation for ineffectiveness was much shorter among ‘inadequate responders’ (median time in years: GR, 4·7, RR: 5·3, IR: 2·0, p=0·03). The proportion of patients with EULAR good or moderate response rate (Lundex corrected) at 1year was higher among ‘rapid responders’ (GR: 22·1%, RR: 39·2%, IR: 6·4%).
    Discussion Safety and efficacy of ABA in early and established RA has been demonstrated in several studies, using population means or – one could say – a single trajectory (Westhovens et al., 2009, 2014; Kremer et al., 2014; Schiff et al., 2011, 2014). The present study focused on trajectory analyses of disease activity following the liquiritin of ABA, using growth mixture modeling to identify subgroups with similar response patterns. This study, which is a collaboration of nine national registries, is the first to analyze trajectories of disease activity in patients with established RA. Analysis of the entire sample identified three types of disease activity trajectories: a larger group of ‘gradual responders’ (91·7%), who improved gradually over time; a group of ‘rapid responders’ (5·6%), who started with a high DAS28 at baseline and improved quickly; and a smaller group of ‘inadequate responders’ (2·6%), who had a stable and relatively high disease activity over the first two years. Overall, socio-demographic and clinical characteristics at baseline were not strongly associated with future trajectory of disease activity after ABA treatment initiation. The importance of identifying these trajectories is reflected in the close association between clinical effectiveness and type of disease activity trajectory: The ‘inadequate responders’ discontinued ABA due to ineffectiveness much earlier compared to gradual and rapid responders. Furthermore, EULAR moderate or good response at 1year was reached by almost none of the “inadequate responders”, compared to more than a third of the ‘rapid responders’. Similarly to studies that examined disease activity trajectories in early RA (Barnabe et al., 2015; Siemons et al., 2014), we identified a large group of gradual responders and a small group of rapid responders. However, the present analysis also detected one group that displayed no improvement of their disease activity over time. The differences in findings could be due to study population or to the smaller sample size of previous studies. Whereas other studies focused on early RA patients on their first DMARD treatment, our analysis included more treatment resistant patients, often initiating a second or third line treatment, who often had long disease duration. In this difficult to treat patient group, it is not surprising to find inadequate responders, a subgroup probably composed of both primary non-responders and patients with secondary failures to this biologic agent. It is also possible that the smaller sample size and limited follow-up of other studies did not allow the detection of small trajectory subgroups. In general, the patients in the three trajectory types could not be separated by baseline characteristics, except for higher disease activity and functional disability at baseline among rapid responders. This finding is in line with previous studies of patients with established RA showing that high DAS28 (Narvaez et al., 2016) and high HAQ score at baseline are associated with good response to bDMARD at 3months (Kristensen et al., 2008). In contrast, studies of patients with early RA (i.e., with less chronicity) described a group of rapid responders with a lower DAS 28 at baseline, and found that patients\' trajectory types differed in socio-demographic characteristics (e.g., sex, race, education) (Barnabe et al., 2015). The discrepancies in findings may be explained by differences in study population. Much research is currently directed at identifying biomarkers to predict response and move towards personalized medicine; however no biomarkers have currently reached a level of discrimination to allow their use in clinical practice. Seropositivity for rheumatoid factor or anti-CCP antibodies has been consistently associated with a better effectiveness of ABA (Gottenberg et al., 2016), but were not associated with a specific disease activity trajectory in this analysis. Clinical effectiveness outcomes strongly differed between trajectories\' types, in line with previous studies of disease activity or disability trajectories over time, in which type of trajectories was associated with mortality (Norton et al., 2013), remission (Siemons et al., 2014), or radiographic progression (Barnabe et al., 2015).