POS1050 SECUKINUMAB LEADS TO IMPROVEMENT ACROSS PSORIATIC ARTHRITIS MANIFESTATIONS OVER 2 YEARS REGARDLESS OF PREVIOUS EXPOSURE TO A TNF INHIBITOR: A POST HOC ANALYSIS OF FUTURE 5
Authors: A. M. Orbai, M. E. Husni, D. D. Gladman, B. Parikh, X. Meng, C. Gaillez, P. J. Mease
Journal: Annals of the Rheumatic Diseases (2021)

Background: The goal of treating psoriatic arthritis (PsA) is to achieve very low disease activity or remission across disease manifestations. In the phase 3 FUTURE 5 study ( NCT02404350 ), patients receiving secukinumab (SEC) demonstrated sustained clinical improvements across PsA manifestations through Week 104. 1 However, the effect of previous tumor necrosis factor inhibitor (TNFi) exposure on achievement of remission across PsA manifestations was not explored. Objectives: To report exploratory efficacy analyses of SEC at Week 104 on stringent endpoints across PsA manifestations in patients who were TNFi naive or inadequate responders (TNF-IR). Methods: Patient data from FUTURE 5 were stratified by previous TNFi exposure and analyzed by treatment arm. At Week 104, patients received SEC 300 or 150 mg with subcutaneous loading dose (LD), SEC 150 mg without LD, or had received placebo up to Week 16 and were switched to SEC 300 or 150 mg between Weeks 16 or 24 based on tender and swollen joint count response. Patients with suboptimal clinical response to SEC 150 mg could escalate to SEC 300 mg after Week 52 per investigator judgment. 2 Exploratory efficacy analyses at Week 104 included resolution of TJC/SJC (0 tender/swollen joints), resolution of enthesitis and dactylitis, 75% improvement in the modified Nail Psoriasis Severity index (mNAPSI75), 100% improvement in the Psoriasis Area and Severity Index (PASI100), very low disease activity (VLDA), and Disease Activity in Psoriatic Arthritis (DAPSA) remission. Descriptive statistics are provided for each endpoint using an observed-case approach. Results: Regardless of previous TNFi exposure, SEC-treated patients achieved several stringent endpoints across PsA domains, including TJC/SJC resolution, resolution of dactylitis/enthesitis, mNAPSI75, and PASI100 at Week 104 (Table 1). TNFi-naive patients generally experienced greater improvements than TNF-IR patients (Table 1 above). Similar trends were observed for achievement of VLDA and DAPSA remission at Week 104 (Figure 1). Conclusion: SEC treatment resulted in sustained achievement of stringent endpoints across key PsA manifestations through Week 104 in both TNFi-naive and TNF-IR patients, with generally greater clinical responses among TNFi-naive patients. References: [1]Mease P, et al. Ann Rheum Dis . 2018;77:890-897. [2]Mease P, et al. Arthritis Rheumatol . 2019;71:(suppl 10) [abstract 1554]. Table 1. Achievement of Key Outcomes Across PsA Manifestations at Week 104 Among TNF-IR and TNFi-Naive Patients Treated With SEC SEC 300 mg SEC 150 mg a SEC 150 mg No Load b PBO–SEC 300 mg PBO–SEC 150 mg c Outcomes, n/M (% ) TNFi-naive n=154 TNF-IR n=68 TNFi-naive n=153 TNF-IR n=67 TNFi-naive n=157 TNF-IR n=65 TNFi-naive n=109 TNF-IR n=44 TNFi-naive n=114 TNF-IR n=39 TJC/SJC resolution 51/140 (36.4) 19/51 (37.3) 46/136 (33.8) 11/46 (23.9) 53/125 (42.4) 14/43 (32.6) 40/90 (44.4) 11/31 (35.5) 32/96 (33.3) 10/28 (35.7) Resolution of dactylitis 42/48 (87.5) 11/16 (68.8) 37/43 (86.0) 16/19 (84.2) 56/62 (90.3) 11/13 (84.6) 35/41 (85.4) 5/7 (71.4) 30/33 (90.9) 10/12 (83.3) Resolution of enthesitis 70/88 (79.5) 22/30 (73.3) 70/85 (82.4) 24/32 (75.0) 50/69 (72.5) 16/26 (61.5) 37/50 (74.0) 12/17 (70.6) 39/56 (69.6) 14/20 (70.0) mNAPSI75 61/73 (83.6) 15/26 (57.7) 66/76 (86.8) 16/23 (69.6) 61/80 (76.3) 13/18 (72.2) 42/51 (82.4) 13/17 (76.5) 34/64 (53.1) 7/14 (50.0) PASI100 34/68 (50.0) 14/29 (48.3) 41/85 (48.2) 5/19 (26.3) 33/73 (45.2) 4/18 (22.2) 23/45 (51.1) 9/18 (50.0) 19/46 (41.3) 6/13 (46.2) IR, inadequate responder; M, number of evaluable patients; mNAPSI, modified Nail Psoriasis Severity Index; PASI, Psoriasis Area and Severity Index; PBO, placebo; SEC, secukinumab; TJC/SJC resolution, 0 tender/swollen joints; TNFi, tumor necrosis factor inhibitor. a Includes 53 TNFi-naive and 23 TNF-IR patients with dose escalation. b Includes 58 TNFi-naive and 19 TNF-IR patients with dose escalation. c Includes 40 TNFi-naive and 12 TNF-IR patients with dose escalation. Figure 1. Acknowledgements: This study was funded by Novartis Pharma AG. The authors thank Prasanthi Mandalay, PhD, of ArticulateScience LLC, for providing medical writing support/editorial support, which was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ, in accordance with Good Publication Practice (GPP3) guidelines ( http://www.ismpp.org/gpp3 ). Disclosure of Interests: Ana-Maria Orbai Consultant of: Janssen, Eli Lilly, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Celgene, Horizon, Janssen, Eli Lilly, and Novartis, M Elaine Husni Consultant of: AbbVie, Amgen, Gilead, Janssen, Eli Lilly, Novartis, Pfizer, Regeneron, and UCB, Grant/research support from: Pfizer, Dafna D Gladman Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Galapagos, Gilead, Janssen, Eli Lilly, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Novartis, Pfizer, and UCB, Bhumik Parikh Employee of: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, Xiangyi Meng Employee of: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, Corine Gaillez Employee of: Novartis Pharma AG, Basel, Switzerland, Philip J Mease Speakers bureau: AbbVie, Amgen, Janssen, Eli Lilly, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Galapagos, Gilead, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Pfizer, Sun Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Gilead, Janssen, Eli Lilly, Novartis, Pfizer, Sun Pharma, and UCB.