Article Text

PDF
THU0414 Secukinumab Inhibits Radiographic Progression in Patients with Psoriatic Arthritis: Data from a Phase 3 Randomized, Multicenter, Double-Blind, Placebo-Controlled Study (Future 1)
  1. D. van der Heijde1,
  2. R. Landewé2,
  3. P. Mease3,
  4. I.B. McInnes4,
  5. P.G. Conaghan5,
  6. L. Pricop6,
  7. G. Ligozio6,
  8. H. Richards7,
  9. S. Mpofu7
  1. 1Leiden University Medical Center, Leiden
  2. 2University of Amsterdam and Atrium Medical Center, Amsterdam, Netherlands
  3. 3Swedish Medical Center and University of Washington, Washington, United States
  4. 4University of Glasgow, Glasgow
  5. 5University of Leeds, Leeds, United Kingdom
  6. 6Novartis Pharmaceuticals Corporation, East Hanover, United States
  7. 7Novartis Pharma AG, Basel, Switzerland

Abstract

Objectives To investigate the effect of secukinumab, a human anti–interleukin-17A monoclonal antibody, on radiographic progression in PsA patients (pts) in the FUTURE 1 study (NCT01392326).

Methods 606 adults with active PsA were randomized to secukinumab or placebo (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. At Wk 16, PBO pts who had ≥20% reduction in both tender and swollen joint count (responders) remained on PBO until Wk 24, and non-responders were re-randomized to secukinumab 75 or 150 mg. The van der Heijde modified Sharp total scores (mTSS), and erosion and joint space narrowing (JSN) scores were determined at baseline, Wks 16/24 (depending on clinical response) and 52. Analysis of effect on radiographic progression at Wk 24 used linear extrapolation for patients with X-ray assessments at Wk 16 and followed a pre-defined hierarchical testing procedure to adjust for multiplicity. Wk 52 analyses used evaluable data. Assessment of no structural progression, defined as a change in mTSS from baseline to Wk 24 of ≤0.5, was included as an exploratory endpoint.

Results Secukinumab significantly inhibited radiographic progression at 24 wks; mean changes in mTSS from baseline to Wk 24 were 0.08 (pooled secukinumab doses), 0.13 (10 IV→150 SC) and 0.02 (10 IV→75 SC) vs 0.57 for PBO. Inhibition of joint structural damage was sustained with secukinumab through Wk 52. In x-ray completers, inhibition of radiographic progression was demonstrated in PBO pts who switched to secukinumab; mean change in mTSS from Wk 24 to Wk 52 was –0.03 (Table). The proportion of pts with no disease progression from baseline to Wk 24 was higher for secukinumab groups (10 IV→150 SC and 10 IV→75 SC, respectively) vs PBO; 82.3% and 92.3% vs 75.7%. Through Wk 24 to Wk 52 the proportion of pts with no disease progression was sustained in the secukinumab groups (85.7% and 85.8%), and increased in pts initially randomized to PBO following active treatment (86.8%).

Conclusions Sustained inhibition of radiographic disease progression was observed with secukinumab through Wk 52. Switching to secukinumab inhibited radiographic disease progression in pts initially randomized to PBO.

Acknowledgements Medical writing support was provided by Rachel Mason at Seren Communications (Tytherington, UK), and was funded by Novartis.

Disclosure of Interest D. Van Der Heijde Grant/research support 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, and Vertex, Consultant for: 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, and Vertex, Paid instructor for: Director of Imaging Rheumatology bv, R. Landewé Grant/research support from: Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB, and Wyeth, Consultant for: Abbott/AbbVie, Ablynx, Amgen, AstraZeneca, Bristol-Myers Squibb, Centocor, GlaxoSmithKline, Novartis, Merck, Pfizer, Roche, Schering-Plough, UCB, and Wyeth, Paid instructor for: RL is director of Rheumatology Consultancy BV, which is a registered company under Dutch law, Speakers bureau: Abbott, Amgen, Bristol-Myers Squibb, Centocor, Merck, Pfizer, Roche, Schering-Plough, UCB, and Wyeth, P. Mease Grant/research support from: AbbVie, Amgen, Biogen Idec, BMS, Celgene, Crescendo, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, and Vertex, Consultant for: AbbVie, Amgen, Biogen Idec, BMS, Celgene, Covagen, Crescendo, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, and Vertex, Speakers bureau: AbbVie, Amgen, Biogen Idec, BMS, Crescendo, Janssen, Lilly, Pfizer, and UCB, I. McInnes Consultant for: Novartis, Amgen, Janssen, BMS, Pfizer, UCB, Abbvie, Celgene, and Lilly, P. Conaghan Consultant for: Abbvie, Merck, Roche, Pfizer, Novartis, and UCB, Speakers bureau: Abbvie, Merck, Roche, Pfizer, Novartis, and UCB, L. Pricop Shareholder of: Novartis, Employee of: Novartis, G. Ligozio Shareholder of: Novartis, Employee of: Novartis, H. Richards Employee of: Novartis, S. Mpofu Shareholder of: Novartis, Employee of: Novartis

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.