Session Type: Abstract Submissions (ACR)
Background/Purpose: The proto-oncogene survivin regulates cell division and inhibits apoptosis. Elevated levels may be found in patients with rheumatoid arthritis (RA) and their presence has been associated with joint destruction. Here, we investigated if survivin may be a marker or predictor of clinical disease activity and/or response to treatment in patients with early RA.
Methods: Serum levels of survivin 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, disease non-active patients (DAS28≤3.2, NAPs) remained on MTX, while active patients (APs) were randomized to triple therapy (MTX+sulfasalazine+hydroxychloroquine) or anti-TNF (MTX+infliximab). Analyses were based on intention-to-treat and performed with respect to baseline (BL) survivin status; conversion status from BL to 3 months; or from 3 to 12 (or 24) months, (+/+) vs. (+/-) or (-/-) vs. (-/+), respectively. Values >0.45 ng/mL were considered (+). Outcome measures included the reductions from BL to 3 months or from 3 to 12 months in the DAS28 and core-set outcomes; actual values at 3, 12, or 24 months; as well as EULAR responses.
Results: Out of 302 patients, 114 (38%) were survivin (+) at BL. The survivin (+) patients were significantly more often RF (+) (81% vs. 58%, p<0.001), but no differences were found over time vs. (-) at BL in the majority of outcome measures.
Among 294 patients with 3-month status, survivin-negative patients (-/-) (n=167) had a significantly better DAS28 and swollen joint count at 12 months vs. 3-month converters (-/+) (n=14) (median 2.89 vs. 3.76, 1.0 vs. 4.5, respectively; p<0.050). Converters to negative (+/-) by 3 months (n=11) vs. non-converters (+/+) (n=28) among NAPs had significantly greater reductions at 3 months in DAS28 and patient’s global visual analog scale (PG-VAS) (3.5 vs. 2.5, 40.0 vs. 23.5, respectively; p<0.010). Among APs, converters (+/-) by 3 months had improvements by 12 months.
Conversion (+/-) from 3 to 12 (or 24) months led to significant reductions among triple therapy from 3 to 12 months (n=12) vs. (+/+) (n=15) (PG-VAS, 19.5 vs. 0.0, p=0.024), which was not observed in the same interval among anti-TNF. The positive DAS28 reduction among triple therapy (+/-) vs. anti-TNF (+/-) (1.52 vs. 0.55, p=0.082) led to significantly more EULAR Good responders from 3 to 12 months (58% (7/12) vs. 0% (0/6), p=0.038).
Conclusion: Survivin status at BL did not predict the 3-month response to MTX. Non-elevated survivin (-/-) leads to better outcomes than (-/+) after 3 months’ MTX treatment, whereas conversion (+/-) by 3 months is associated with greater clinical improvements than (+/+) primarily among MTX responders at 3 months, but also by 12 months among 3-month MTX non-responders. Among patients randomized to triple therapy, those whose survivin converted (+/-) from 3 to 12 months had better 12-month outcomes than non-converters (+/+). This association was not seen for patients randomized to anti-TNF, suggesting that survivin may be associated with TNF-independent inflammatory pathways.
R. F. van Vollenhoven,
AbbVie, BMS, GSK, Pfizer, Roche, UCB,
AbbVie, Biotest, BMS, Crescendo, GSK, Janssen, Lilly, Merck, Pfizer, Roche, UCB, Vertex,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-survivin-in-early-rheumatoid-arthritis/