NDLI: Serum survivin predicts responses to treatment in active rheumatoid arthritis: a post hoc analysis from the SWEFOT trial

Content Provider	Springer Nature : BioMed Central
Author	Levitsky, Adrian Erlandsson, Malin C. van Vollenhoven, Ronald F. Bokarewa, Maria I.
Abstract	Background The identification of biomarkers that predict optimal and individual choices of treatment for patients with rheumatoid arthritis gains increasing attention. The purpose of this study was to investigate if the proto-oncogene survivin might aid in treatment decisions in early rheumatoid arthritis. Methods Serum survivin levels were measured in 302 patients who completed the Swedish pharmacotherapy (SWEFOT) trial at baseline, 3, 12, and 24 months. Survivin levels > 0.45 ng/mL were considered positive. Based on the survivin status, core set outcomes measuring disease activity, functional disability, as well as global health and pain were evaluated after methotrexate (MTX) monotherapy at 3 months, and at 12 and 24 months of follow-up. Treatment of non-responders was randomly intensified with either a combination of disease-modifying antirheumatic drugs (triple therapy: MTX, sulfasalazine, and hydroxychloroquine) or by adding antibodies against tumor necrosis factor (anti-TNF). Results Antirheumatic treatment resulted in an overall decrease of serum survivin levels. Survivin-positive patients at baseline who initially responded to MTX had a higher risk of disease re-activation (OR 3.21 (95 % CI 1.12–9.24), P = 0.032) and failed to improve in their functional disability (P = 0.018) if having continued on MTX monotherapy compared to survivin-negative patients. Ever-smokers who were survivin-positive were less likely to respond to MTX than those who were survivin-negative (OR 1.91 (1.01–3.62), P = 0.045). In survivin-positive patients, triple therapy led to better improvements in disease activity than did MTX + anti-TNF. At 24 months, survivin-positive patients randomized to anti-TNF had a higher risk of active disease than those randomized to triple therapy (OR 3.15 (1.09–9.10), P = 0.037). Discussion We demonstrate for the first time that survivinis a valuable serologic marker that can distinguish drug-specific clinical responses in early rheumatoid arthritis through the pragmatic clinical setting of the care-based SWEFOT trial. Although treatment response cannot solely be attributable to survivinstatus, per protocol sensitivity analyses confirmed the superior effect of triple therapy on survivin-positive patients. Conclusions Survivin-positive patients have poor outcomes if treated with MTX monotherapy. A decrease of survivin levels during treatment is associated with better clinical responses. For survivin-positive patients who fail MTX, triple therapy is associated with better outcomes than anti-TNF therapy. Trial registration WHO database at the Karolinska University Hospital: CT20080004 ; ClinicalTrials.gov: NCT00764725 , registered 1 October 2008.
Related Links	https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-015-0485-2.pdf
Ending Page	10
Page Count	10
Starting Page	1
File Format	HTM / HTML
ISSN	17417015
DOI	10.1186/s12916-015-0485-2
Journal	BMC Medicine
Issue Number	1
Volume Number	13
Language	English
Publisher	BioMed Central
Publisher Date	2015-09-30
Access Restriction	Open
Subject Keyword	Medicine Public Health Biomedicine Survivin Rheumatoid arthritis Biomarkers Methotrexate Disease-modifying antirheumatic drugs Anti-TNF Disease activity Functional disability Medicine/Public Health
Content Type	Text
Resource Type	Article
Subject	Medicine
Journal Impact Factor	7.1/2023
5-Year Journal Impact Factor	8.8/2023

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