Background Survivin is an oncological biomarker. In rheumatoid arthritis (RA), elevated serum survivin is common and has been used to predict disease onset and progressive joint damage.
Objectives We investigated the predictive capacity of survivin in clinical disease activity and/or response to various antirheumatic treatments in patients with early RA.
Methods Survivin 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). Survivin levels >0.45 ng/mL were considered positive. Based on survivin status over 24 months, core-set outcomes (i.e. DAS28, HAQ, pain & global VAS) were evaluated at 3, 12, and 24 months.
Results Over one-third of all patients (n=114) were survivin-positive at baseline. Survivin-positive ever-smokers (51/71 vs. 64/112, OR 1.91 [95% CI 1.01-3.62], p=0.045) and survivin-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, survivin-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, survivin-positive MTX-responders who continued monotherapy had a higher risk of disease re-activation on MTX compared to the survivin-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.
Survivin-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>1.2, 63% & 60% vs. 31%, p=0.053, p=0.046, respectively). Among survivin-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 survivin groups. Survivin-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).
Conclusions Survivin-positive patients have worse 24-month outcomes than survivin-negative patients if treated with MTX monotherapy, but conversion to survivin-negative is associated with a good and stable response to MTX monotherapy. For survivin-positive patients with early RA who fail MTX, triple therapy is associated with a better likelihood for response than anti-TNF therapy.
Disclosure of Interest 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
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