Session Information
Date: Monday, November 9, 2015
Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy Poster II
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose:
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. We investigated the predictive capacity of survivin for response to various antirheumatic treatments in patients with early RA.
Methods:
Survivin levels in serum were measured using ELISA in 302 patients enrolled in the Swedish pharmacotherapy (SWEFOT) trial at baseline and at 3, 12, and 24 months of follow-up. Survivin levels >0.45 ng/mL were considered positive. 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). The core-set outcomes (i.e. DAS28, HAQ, pain & global VAS) were evaluated at 3, 12, and 24 months in relation to survivin status.
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 4.30 [0.95, 19.49], p=0.037) responded seldom to MTX.
At 3 months, survivin-positive patients among MTX responders who converted to negative (n=11) had greater reductions in DAS28, HAQ and global VAS vs. those who remained positive (n=28). A delay in improvement from functional disability was shown among the patients who remained positive, as the HAQ value was already higher despite MTX response. At 12 months, survivin-positive MTX responders who continued monotherapy had a higher risk of disease re-activation compared to survivin-negative patients (12/36 vs. 7/52, OR 3.21 [1.12-9.24], p=0.032) and deteriorated in HAQ over 24 months.
Among survivin-positive patients on triple therapy, converting to negative (n=19) was associated with a lower DAS28 at 12 months (2.34 vs. 4.12, p=0.046) and a higher frequency of low disease activity (DAS≤3.2, 86% vs. 37%, p=0.056) at 24 months vs. converting to positive (n=7). Lower pain (p=0.048) and global VAS (p=0.015) at 12 months was also found 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. The patients on triple therapy who converted to negative attained a lower DAS28 at 12 months compared to those on anti-TNF (2.34 vs. 3.43, p=0.045). Survivin-positive patients on anti-TNF had a higher risk to have active disease at 24 months compared to those on triple therapy (DAS28>3.2, 16/29 vs. 9/32, OR 3.15 [1.09-9.10], p=0.037; DAS28, 3.50 vs. 2.37, p=0.020).
Conclusion:
Survivin-positive patients who initially respond to MTX monotherapy have worse long-term outcomes than survivin-negative patients, and conversion from positive to negative is associated with a good response to conventional disease-modifying antirheumatic drugs. For survivin-positive patients with early RA who fail MTX, triple therapy is associated with a better likelihood for response than anti-TNF therapy.
To cite this abstract in AMA style:
Levitsky A, Erlandsson MC, van Vollenhoven RF, Bokarewa MI. Serum Survivin Predicts Responses to Treatment in Active Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/serum-survivin-predicts-responses-to-treatment-in-active-rheumatoid-arthritis/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-survivin-predicts-responses-to-treatment-in-active-rheumatoid-arthritis/