Secukinumab, a Human Anti–Interleukin-17A Monoclonal Antibody, Improves Active Psoriatic Arthritis and Inhibits Radiographic Progression: Efficacy and Safety Data from a Phase 3 Randomized, Multicenter, Double-Blind, Placebo-Controlled Study

Philip J. Mease¹, Iain B. McInnes², Bruce Kirkham³, Arthur Kavanaugh⁴, Proton Rahman⁵, Désirée van der Heijde⁶, Robert Landewé⁷, Peter Nash⁸, Luminita Pricop⁹, Jiacheng Yuan¹⁰, Hanno Richards¹¹ and Shephard Mpofu¹², ¹Swedish Medical Center and University of Washington, Seattle, WA, ²University of Glasgow, Glasgow, United Kingdom, ³Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom, ⁴UCSD School of Medicine, La Jolla, CA, ⁵Faculty of Medicine, Memorial University of Newfoundland, St. John's, NF, Canada, ⁶Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands, ⁷Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands, ⁸University of Queensland, Brisbane, Australia, ⁹Integrated Hospital Care (IHC) Franchise, Novartis Pharmaceuticals Corporation, East Hanover, NJ, ¹⁰Novartis Pharmaceuticals Corporation, East Hanover, NJ, ¹¹Clinical Immunology / Dermatology, Novartis Pharma AG, Basel, Switzerland, ¹²Novartis Pharma AG, Basel, Switzerland

Meeting: ACR/ARHP Annual Meeting 2014

Keywords: monoclonal antibodies, Psoriatic arthritis, randomized trials and treatment

Session Information

Title: Spondyloarthropathies and Psoriatic Arthritis II - Novel Treatments Psoriatic Arthritis

Session Type: Abstract Submissions (ACR)

Background/Purpose

Secukinumab has demonstrated significant and rapid efficacy in the treatment of psoriasis in two phase 3 studies. We present the first randomized, multicenter, double-blind, placebo (PBO)-controlled phase 3 study to assess the efficacy and safety of secukinumab in patients (pts) with PsA (FUTURE 1; NCT01392326).

Methods

606 adults with active, moderate to severe PsA were randomized to secukinumab or PBO. Pts on secukinumab received 10 mg/kg i.v. loading dose at baseline, Week (Wk) 2 and Wk 4, then either 75 mg s.c. (10 IV→75 SC) or 150 mg s.c. (10 IV→150 SC) every 4 wks from Wk 8. PBO was given on the same schedules. Patients naïve to anti-TNF therapy (~70%) and those intolerant of or inadequate responders to anti-TNF therapy (TNF-IR; ~30%), were stratified across groups. Statistical analyses for the primary and multiple secondary endpoints used non-responder imputation (binary variables), mixed-effects repeated measures model (continuous variables), and linear extrapolation (radiographic data), following a pre-defined hierarchical hypothesis testing strategy to adjust for multiplicity.

Results

Demographics and baseline characteristics were balanced between groups. Both 10 IV→75 SC and 10 IV→150 SC demonstrated significantly higher ACR20 responses vs. PBO at Wk 24 (50.5% and 50.0% vs. 17.3%, respectively; P< 0.0001 vs. PBO). All pre-specified secondary endpoints, including dactylitis, enthesitis, SF36-PCS, HAQ-DI, DAS28-CRP, ACR50, PASI 75, PASI 90, and mTSS score were achieved by Wk 24 and reached statistical significance; active dose separated from PBO as early as Wk 1 for ACR20, DAS28-CRP, and HAQ-DI. Drug exposure levels were similar in the secukinumab groups up to the primary endpoint due to i.v. loading. Improvements in all primary and secondary endpoints were sustained through Wk 52. At Wk 52, ACR 20/50/70 responses, using an observed analysis, were 66.9%, 38.4% and 25.6% for 10 IV→75 SC and 69.5%, 50.0% and 28.2% for 10 IV→150 SC. In both TNF-naïve and TNF-IR groups, secukinumab demonstrated superiority at Wk 24 in ACR20/50/70, PASI 75/90, HAQ-DI, SF36-PCS, dactylitis and enthesitis at both doses and the effect was maintained through Wk 52. Secukinumab significantly inhibited radiographic structural joint damage at Wk 24 vs. PBO. AEs at Wk 16: 60.4% (10 IV→75 SC), 64.9% (10 IV→150 SC) and 58.4% (PBO); non-fatal SAE rates: 2.5%, 4.5% and 5.0%, respectively. Mean, median, and maximum exposures: 438.5, 456.0 and 721 days; AE/non-fatal SAE rates: 78.1%/8.6% and 82.4%/12.9% in pts who received secukinumab 75 mg s.c. or 150 mg s.c., respectively, at any point in the study.

Table. Summary of selected 24-week efficacy results
Week 24 Data	Secukinumab 10 mg/kg IV → 75 mg SC	Secukinumab 10 mg/kg IV → 150 mg SC	PBO
ACR20 (% responders)	50.5*	50.0*	17.3
ACR50 (% responders)	30.7*	34.7*	7.4
ACR70 (% responders)	16.8*	18.8*	2.0
DAS28-CRP (mean change from BL) Overall (n=606)	–1.67*	–1.62*	–0.77
^aDactylitis (presence of, %) Overall (n=324)	43.3*	51.9*	84.5
^aEnthesitis (presence of, %) Overall (n=372)	51.2*	54.0*	87.2
*P < 0.0001 vs. PBO; ^aData from pts with dactylitis (n = 324) and enthesitis (n = 372) at baseline. ACR, American College of Rheumatology response criteria; BL, baseline; DAS28-CRP, Disease Activity Score 28 using C-reactive protein; IV, intravenous; pts, patients; SC, subcutaneous

Conclusion

In this first phase 3 trial to evaluate highly selective IL-17A inhibition in pts with PsA, secukinumab provided rapid, clinically significant and sustained improvements in signs and symptoms, and inhibited joint structural damage. Secukinumab was well tolerated through 52 wks.

Disclosure:

P. J. Mease,

Research grants from AbbVie, Amgen, Biogen Idec, BMS, Celgene, Crescendo, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, and Vertex,

Consulting fees from AbbVie, Amgen, Biogen Idec, BMS, Celgene, Covagen, Crescendo, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, and Vertex,

Speakers’ bureau for AbbVie, Amgen, Biogen Idec, BMS, Crescendo, Janssen, Lilly, Pfizer, and UCB,

I. B. McInnes,

Consulting fees from Novartis, Amgen, Janssen, BMS, Pfizer, UCB, Abbvie, Celgene and Lilly,

B. Kirkham,

Research grants from AbbVie and UCB,

Consulting fees from Novartis, AbbVie, BMS, Lilly, and MSD,

Speakers’ bureau for BMS, MSD, and UCB,

A. Kavanaugh,

Consulting fees from Novartis ,

P. Rahman,

Consulting fees for Abbott, AbbVie, Amgen, BMS, Celgene, Janssen, Novartis, Pfizer and Roche,

D. van der Heijde,

Consulting fees from AbbVie, Amgen, AstraZeneca, Augurex, BMS, Celgene, Centocor, Chugai, Covagen, Daiichi, Eli-Lilly, Galapagos, GSK, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB, Vertex. D,

Research grants from AbbVie, Amgen, AstraZeneca, Augurex, BMS, Celgene, Centocor, Chugai, Covagen, Daiichi, Eli-Lilly, Galapagos, GSK, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB, Vertex. D,

R. Landewé,

Consulting fees from Abbott/AbbVie, Ablynx, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Centocor, GlaxoSmithKline, Novartis, Merck, Pfizer, Roche, Schering-Plough, UCB, Wyeth,

Advisory boards for Abbott/AbbVie, Ablynx, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Centocor, GlaxoSmithKline, Novartis, Merck, Pfizer, Roche, Schering-Plough, UCB, Wyeth,

Research grants from Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB, Wyeth,

Speaker fees: Abbott, Amgen, Bristol-Myers Squibb, Centocor, Merck, Pfizer, Roche, Schering-Plough, UCB, Wyeth,

Rheumatology Consultancy BV,

P. Nash,

Research grants from Novartis, Abbvie, Roche, Pfizer, BMS, Janssen, and Celgene,

Honoraria for lectures and advice from Novartis, Abbvie, Roche, Pfizer, BMS, Janssen, and Celgene,

L. Pricop,

Employee of Novartis ,

Novartis stock,

J. Yuan,

Employee of Novartis ,

H. Richards,

Employee of Novartis ,

S. Mpofu,

Novartis stock ,

Employee of Novartis ,

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