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 ≤1; 2) swollen joint count ≤1; 3) Psoriasis Activity and Severity Index ≤1 or psoriasis affecting <3% body surface area at BL; 4) pt pain VAS ≤15; 5) pt global disease activity VAS ≤20; 6) HAQ-DI ≤0.5; 7) tender entheseal points ≤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 (≤2 yrs vs >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 ≤2 yrs since diagnosis vs those >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 (Figure).
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.
Mease et al. J Rheumatol 2013;40:647–52
Acknowledgement The study was sponsored by Novartis Pharma AG.
Disclosure of Interest L. Coates Grant/research support from: Abbvie, Pfizer, Janssen, Consultant for: Abbvie, Celgene, Pfizer, UCB, MSD, Boehringer Ingelheim, Novartis, Lilly, P. Mease Grant/research support from: Abbvie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, Consultant for: Abbvie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, Speakers bureau: Abbvie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, B. Kirkham Grant/research support from: Abbvie, Novartis and Roche, Consultant for: Abbott, BMS, Chugai, MSD, Novartis, Pfizer, Roche and UCB, Speakers bureau: Abbott, BMS, Chugai, MSD, Novartis, Pfizer, Roche and UCB, L. McLeod Consultant for: Novartis through employment at RTI Health Solutions, Employee of: RTI Health Solutions, S. Mpofu Shareholder of: Novartis, Employee of: Novartis, C. Karyekar Shareholder of: Novartis, Employee of: Novartis, K. Gandhi Shareholder of: Novartis, Employee of: Novartis