THU0088 Serum Survivin Predicts Treatment Response in Active Rheumatoid Arthritis
Authors: A. Levitsky, M. Erlandsson, R.F. van Vollenhoven, M.I. Bokarewa
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> <i>Survivin</i> is an oncological biomarker. In rheumatoid arthritis (RA), elevated serum <i>survivin</i> is common and has been used to predict disease onset and progressive joint damage. <h3>Objectives</h3> We investigated the predictive capacity of <i>survivin</i> in clinical disease activity and/or response to various antirheumatic treatments in patients with early RA. <h3>Methods</h3> <i>Survivin</i> levels from serum were measured using ELISA at baseline in 302 patients enrolled in the Swedish pharmacotherapy (SWEFOT) trial with follow-up at 3, 12 and 24 months. After methotrexate (MTX) monotherapy for 3 months, responders (DAS28≤3.2) remained on MTX, while non-responders were randomized to triple therapy (MTX+sulfasalazine+hydroxychloroquine) or anti-TNF (MTX+infliximab). <i>Survivin</i> levels &gt;0.45 ng/mL were considered positive. Based on <i>survivin</i> status over 24 months, core-set outcomes (i.e. DAS28, HAQ, pain &amp; global VAS) were evaluated at 3, 12, and 24 months. <h3>Results</h3> Over one-third of all patients (n=114) were <i>survivin</i>-positive at baseline. S<i>urvivin</i>-positive ever-smokers (51/71 vs. 64/112, OR 1.91 [95% CI 1.01-3.62], p=0.045) and <i>survivin</i>-negative patients who converted to positive over 24 months (13/161 vs. 2/100, OR 4.39 [0.97, 19.88], p=0.037) responded seldom to MTX. At 3 months, <i>survivin-</i>positive patients who converted negative (n=11) had greater reductions in DAS28 (p=0.002), HAQ (p=0.011) and global VAS (p=0.025) vs. those who remained positive (n=28), which were maintained over 24 months. At 12 months, <i>survivin</i>-positive MTX-responders who continued monotherapy had a higher risk of disease re-activation on MTX compared to the <i>survivin</i>-negative patients (12/36 vs. 7/52, OR 3.21 [1.12-9.24], p=0.032) and showed no improvement in HAQ over 24 months. <i>Survivin</i>-positive MTX non-responders who converted to negative (n=32) or remained negative (n=83) had greater improvements from 3 to 12 months than those who converted to positive (n=13) (ΔDAS28&gt;1.2, 63% &amp; 60% vs. 31%, p=0.053, p=0.046, respectively). Among <i>survivin</i>-positive patients on triple therapy, converting to negative (n=19) yielded a lower DAS28 at 12 months (2.34 vs. 4.12, p=0.046) and a high frequency of DAS≤3.2 (86% vs. 37%, p=0.056) at 24 months vs. converting to positive (n=7). They also had lower pain (p=0.048) and global VAS (p=0.015) at 24 months compared to the same subgroup, which was not observed among anti-TNF – where no differences in core-set outcomes were observed between the <i>survivin</i> groups. <i>Survivin</i>-positive patients on anti-TNF had a higher risk to have active disease at 24 months compared to those on triple therapy (16/29 vs. 9/32, OR 3.15 [1.09-9.10], p=0.037). <h3>Conclusions</h3> <i>Survivin</i>-positive patients have worse 24-month outcomes than <i>survivin</i>-negative patients if treated with MTX monotherapy, but conversion to <i>survivin-</i>negative is associated with a good and stable response to MTX monotherapy. For <i>survivin</i>-positive patients with early RA who fail MTX, triple therapy is associated with a better likelihood for response than anti-TNF therapy. <h3>Disclosure of Interest</h3> A. Levitsky: None declared, M. Erlandsson: None declared, R. van Vollenhoven Grant/research support from: AbbVie, BMS, GSK, Pfizer, Roche, UCB, Consultant for: AbbVie, Biotest, BMS, Crescendo, GSK, Janssen, Lilly, Merck, Pfizer, Roche, UCB, Vertex, M. Bokarewa: None declared