Background/Purpose: Secukinumab (SEC), a fully human monoclonal antibody that selectively neutralizes IL-17A, provided significant and sustained improvement in the signs and symptoms of active PsA, with sustained resolution of enthesitis in Phase 3 FUTURE 2 and FUTURE 3 studies.^1,2 This post-hoc analysis evaluated the effect of SEC on resolution of enthesitis count (EC; defined by Leeds Enthesitis Index) in PsA patients (pts) using pooled data from FUTURE 2 and FUTURE 3 studies.

Methods:  Study designs have been reported previously.^1,2 The results are reported only for SEC 300 and 150 mg (approved doses). Pts with baseline (BL) enthesitis (BLE) or without BLE (No BLE) were included. Evaluation through Week (Wk) 104 included: time to first resolution of enthesitis (i.e. EC = 0); shift analysis of BL EC (1 or 2 or 3‒6) to full resolution (FR) and partial resolution (PR; reduction of EC) at Wks 24 and 104; and number of new enthesitis sites developed in pts with No BLE. Individual status over time with respect to resolution of EC was also determined by heat map analysis using last observation carried forward. Data are as observed in the overall population; time to first resolution of enthesitis was analyzed in the overall population and by prior use of tumor necrosis factor inhibitor (TNFi-naïve and -inadequate responders [IR]).

Results: A total of 466 pts had BLE with a mean EC of 3.1±1.6, and 246 pts had no BLE. Median days to resolution of EC in BLE pts for SEC 300, 150 mg and PBO groups were 57, 85 and 167 in overall population; 57, 85 and 120 in TNFi-naïve pts; and 92, 82 and 169 in TNFi-IR pts, respectively. In pts with BL EC = 1 or 2, 72%/61% (SEC 300 mg), 71%/66% (SEC 150 mg) and 45%/44% (PBO), respectively, achieved FR at Wk 24, with FR in SEC groups sustained or increased to 77%/81% (SEC 300 mg) and 75%/88% (SEC 150 mg) at Wk 104. In BL EC = 3‒6, 81% (SEC 300 mg), 73% (SEC 150 mg) and 71% (PBO) of pts achieved FR and PR at Wk 24, with an increase of FR and PR to 88% (in both SEC 300 and 150 mg) at Wk 104 (Figure). A total of 89% of pts with No BLE did not develop enthesitis by Wk 104. Heat map analysis showed that SEC-treated pts at individual level had more resolution of EC than PBO pts at Wk 24.

Conclusion: Time to resolution of enthesitis was earlier with SEC than PBO in the overall population, with faster resolution observed in TNFi-naïve than TNFi-IR pts. Majority of SEC-treated pts with BL EC = 1 or 2 had FR by Wk 24, with further improvement by Wk 104. In pts with BL EC = 3‒6, greater improvement was observed with SEC 300 mg vs PBO in the proportion of pts with FR and PR of enthesitis at Wk 24; further improvements were observed in both SEC groups at Wk 104.

References: 1. McInnes IB, et al. Lancet 2015;386:1137–2. Nash P, et al. Arthritis Res Ther 2018;20:47.