Background: Minimal disease activity (MDA), a validated composite measure in PsA, is gaining acceptance as a target for achieving substantial disease control. Objectives: Secukinumab (SEC), an anti–IL-17A monoclonal antibody, significantly improved the signs and symptoms of PsA over 52 wks in the FUTURE 2 study. This post-hoc exploratory analysis assessed MDA response rates through 52 wks.
Methods: 397 patients (pts) with active PsA were randomized to subcutaneous (SC) SEC (300 mg, 150 mg, or 75 mg) or placebo (PBO) at baseline (BL), Wks 1, 2, and 3, and every 4 wks (q4w) from Wk 4. PBO pts were re-randomized to SEC 300 or 150 mg SC q4w from Wk 16 or 24, depending upon clinical response. Pts were considered in MDA when they met at least 5 of the following 7 criteria: 1) tender joint count less than or equal to 1; 2) swollen joint count less than or equal to 1; 3) Psoriasis Activity and Severity Index ≤1 or psoriasis affecting less than 3% body surface area at BL; 4) pt pain VAS less than or equal to15; 5) pt global disease activity VAS less than or equal to 20; 6) HAQ-DI less than or equal to 0.5; 7) tender entheseal points less than or equal to 1. MDA was assessed in the overall population and in pts stratified by prior anti-tumor necrosis factor (anti-TNF) therapy use (anti–TNF-naïve and inadequate response/intolerance to these agents [anti–TNF-IR]) and disease duration (less than or equal to 2 yrs vs greater than 2 yrs since diagnosis). Observed data are shown. 75 mg data are not reported as this was not considered an effective dose (no secondary endpoints were met).
Results: In the overall population, 23/100 (23%) and 27/97 (28%) pts achieved MDA at Wk 16 with SEC 150 mg and 300 mg, respectively, vs 9/88 (10%) pts with PBO; these response rates were sustained through Wk 52 (150 mg: 29/88 [33%]; 300 mg: 33/93 [35%]). In the anti–TNF-naïve cohort, a higher proportion of pts achieved MDA at Wk 16 with SEC 150 mg (20/63 [32%]) or 300 mg (22/65 [34%]) vs PBO (8/58 [14%]), with response rates sustained through Wk 52 (150 mg: 23/59 [39%]; 300 mg: 26/63 [41%]). Lower rates were observed in anti–TNF-IR pts (SEC vs PBO at Wk 16: 150 mg, 3/37 [8%]; 300 mg, 5/32 [16%]; PBO, 1/30 [3%]; Wk 52: 150 mg, 6/29 [21%]; 300 mg, 7/30 [23%]). The proportion of pts achieving MDA at Wk 16 and Wk 52 in the overall population was greater for those less than or equal to 2 yrs since diagnosis vs those greater than 2 yrs since diagnosis for both SEC 150 mg and 300 mg. The proportion of pts achieving MDA with SEC at Wk 16 was higher in anti–TNF-naïve pts with low disease duration vs pts with longer disease duration, and higher in the anti–TNF-naïve cohort than the anti–TNF-IR cohort at all times.
Conclusions: SEC pts had higher MDA response rates vs PBO pts at Wk 16, with response rates sustained through Wk 52. Response rates were consistent with those previously reported with anti-TNF therapies in comparable pt populations.1 This study is the first to report MDA in anti–TNF-IR pts. The finding that greater MDA can be achieved in early anti–TNF-naive PsA pts warrants further research.
