Secukinumab Provides Sustained Improvements in the Signs and Symptoms of Active Psoriatic Arthritis: 104 Weeks Results from a Phase 3 Trial

Iain B McInnes¹, Philip J Mease², Christopher T. Ritchlin³, Proton Rahman⁴, Alice B Gottlieb⁵, Bruce Kirkham⁶, Radhika Kajekar⁷, Evie Maria Delicha⁸, Luminita Pricop⁹ and Shephard Mpofu⁸, ¹University of Glasgow, Glasgow, Great Britain, ²Swedish Medical Center and University of Washington, Seattle, WA, ³Allergy Immunology & Rheumatology, University of Rochester Medical Center, Rochester, NY, ⁴Rheumatology, St Claires Mercy Hospital, St Johns, NF, Canada, ⁵Tufts University School of Medicine, Boston, MA, ⁶Guy's & St Thomas' NHS Foundation Trust, London, United Kingdom, ⁷One Health Plaza, Novartis Pharmaceuticals Corporation, East Hanover, NJ, ⁸Novartis Pharma AG, Basel, Switzerland, ⁹Novartis Pharmaceuticals Corporation, East Hanover, NJ

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Biologics, interleukins (IL), monoclonal antibodies, psoriatic arthritis and treatment

Session Information

Date: Tuesday, November 15, 2016

Title: Spondylarthropathies and Psoriatic Arthritis – Clinical Aspects and Treatment - Poster III

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Secukinumab, a fully human anti–IL-17A monoclonal antibody, significantly improved signs and symptoms of psoriatic arthritis (PsA) over 52 weeks (wks) in FUTURE 2 study (NCT01752634).^1,2Here we present longer-term (104 wks) efficacy and safety data from this study.

Methods: Overall, 397 patients (pts) with active PsA were randomized to receive s.c. secukinumab (300, 150, or 75 mg) or placebo (PBO) at baseline, Wks 1, 2, 3, and 4, and every 4 wks (q4w) thereafter. PBO pts were re-randomized to secukinumab 300 or 150 mg s.c. q4w depending upon ACR20 response at Wk 16; pts were classified as responders (≥20% improvement from baseline in tender and swollen joint counts) or non-responders, with non-responders switching at Wk 16 and responders at Wk 24. Exploratory endpoints assessed at Wk 104 are from pts originally randomized to secukinumab at the beginning of the trial and included ACR20/50/70, PASI 75/90, DAS28-CRP, SF-36 PCS, HAQ-DI, dactylitis, and enthesitis. Data were assessed by multiple imputation applied to missing binary variables and mixed-model repeated measures for continuous variables. Analyses stratified by anti-TNFα status (anti–TNFα-naïve and anti–TNFα-inadequate response or intolerance to these agents [IR]) were pre-specified and are reported as observed. Safety analysis included all patients who received ≥1 dose of secukinumab and data presented as exposure adjusted incidence rates (EAIR) per 100 pt-years over entire treatment period.

Results: In total, 86/100 (86.0%), 76/100 (76.0%), and 65/99 (65.7%) pts in the secukinumab 300, 150, and 75 mg groups respectively completed 104 wks. At Wk 104, ACR20 response rates in the 300, 150, and 75 mg groups were 69.9%, 64.7%, and 50.1%, respectively. Sustained clinical improvements were observed through Wk 104 with secukinumab across other clinically important domains of PsA (Table). Responses were sustained through Wk 104 in anti‒TNFα-naïve pts and anti‒TNFα-IR. ACR20 response rates at Wk 104 in anti‒TNFα-naïve pts were 80.4%, 86.8%, and 68.6% with 300, 150, and 75 mg, respectively; corresponding rates in anti‒TNFα-IR pts were 60.7%, 41.7%, and 43.8%, respectively. Over the entire treatment period (mean [±SD] exposure to secukinumab of 709±210.99 days) the incidence, type and severity of adverse events were consistent with those reported previously. Specifically, EAIR for serious infections/infestations, candida infections, inflammatory bowel disease, malignant/unspecified tumors, and major adverse cardiac events with secukinumab were 1.6, 2.3, 0.5, 1.3, and 0.3, respectively.

Conclusion: Secukinumab 300 and 150 mg provided sustained improvements in signs and symptoms and multiple clinical domains of active PsA through 2 years of therapy. Secukinumab was well tolerated, with a safety profile consistent with that reported previously. References: 1. McInnes IB, et al. Lancet 2015;386:1137–46. 2. McInnes IB, et al. Ann Rheum Dis. 2015;74:352‒3.

Table: Summary of Efficacy Results at Wk 104
Variable	Secukinumab 300 mg s.c. (N = 100)	Secukinumab 150 mg s.c. (N = 100)	Secukinumab 75 mg s.c. (N = 99)
ACR20, % responders	69.4	64.4	50.3
ACR50, % responders	50.6	36.0	28.2
ACR70, % responders	33.1	23.1	14.9
^aPASI 75, % responders	79.5	73.3	58.4
^aPASI 90, % responders	69.6	52.5	33.7
SF-36 PCS, LS mean change from BL (SE)	6.8 (0.85)	5.0 (0.87)	4.1 (0.91)
DAS28-CRP, LS mean change from BL (SE)	‒1.9 (0.12)	‒1.7 (0.12)	‒1.5 (0.13)
HAQ-DI, LS mean change from BL (SE)	‒0.58 (0.05)	‒0.48 (0.06)	‒0.27 (0.06)
^bResolution of enthesitis, % responders	71.5	61.8	68.4
^cResolution of dactylitis, % responders	79.9	78.0	88.6
^aPASI responses assessed in pts with psoriasis affecting ≥3% body surface area at BL (300 mg: n = 41; 150 mg: n = 58; 75 mg: n = 50); ^bAssessed in patients (n = 56 [300 mg s.c], 64 [150 mg s.c.], and 67 [75 mg s.c]) with this symptom at BL; ^cAssessed in patients (n = 46 [300 mg s.c], 32 [150 mg s.c.], and 33 [75 mg s.c]) with this symptom at BL. BL, baseline; DAS28-CRP, 28-joint disease activity score using C-reactive protein; HAQ-DI, health assessment questionnaire-disability index;LS, least squares; N, number of patients randomized; PASI, psoriasis area and severity index;SE, standard error; SF-36 PCS, short form-36 physical component summary

Disclosure: I. B. McInnes, Abbvie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, and UCB, 2,Abbvie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, and UCB, 5,Abbvie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, and UCB, 8; P. J. Mease, Abbvie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, and UCB, 2,Abbvie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, and UCB, 5,Abbvie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, and UCB, 8; C. T. Ritchlin, Amgen, UCB, Abbvie, Novartis, and Janssen, 2,Amgen, UCB, Abbvie, Novartis, and Janssen, 5; P. Rahman, Abbott, Abbvie, Amgen, BMS, Celgene, Janssen, Novartis, Pfizer and Roche, 5,Pharmaceutical companies dealing with biologic agents in rheumatology, 9; A. B. Gottlieb, Amgen Inc., Astellas, Akros, Centocor (Janssen) Inc. , Celgene Corp., Bristol Myers Squibb Co., Beiersdorf Inc., Abbott Labs. (Abbvie), DUSA, TEVA, Actelion, UCB, Novo Nordisk, Novartis, Dermipsor Ltd., Incyte, Pfizer, Canfite, Lilly, Coronado, Vertex, Ka, 5,Centocor (Janssen) Inc., Amgen, Abbott (Abbvie), Novartis, Celgene, Pfizer, Lilly, Coronado, Levia, Merck, and Xenoport, 2; B. Kirkham, Abbvie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Roche, and UCB, 2,Abbvie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Roche, and UCB, 5,Abbvie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Roche, and UCB, 8; R. Kajekar, Novartis Pharmaceuticals Corporation, 3,Novartis Pharmaceuticals Corporation, 1; E. M. Delicha, Novartis Pharma AG, 1,Novartis Pharma AG, 3; L. Pricop, Novartis, 1,Novartis, 3; S. Mpofu, Novartis Pharma AG, 1,Novartis Pharma AG, 3.

To cite this abstract in AMA style:

McInnes IB, Mease PJ, Ritchlin CT, Rahman P, Gottlieb AB, Kirkham B, Kajekar R, Delicha EM, Pricop L, Mpofu S. Secukinumab Provides Sustained Improvements in the Signs and Symptoms of Active Psoriatic Arthritis: 104 Weeks Results from a Phase 3 Trial [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/secukinumab-provides-sustained-improvements-in-the-signs-and-symptoms-of-active-psoriatic-arthritis-104-weeks-results-from-a-phase-3-trial/. Accessed .

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