ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: L1

Secukinumab, a Human Anti-Interleukin-17A Monoclonal Antibody, Improves Active Psoriatic Arthritis: 24-Week Efficacy and Safety Data from a Phase 3 Randomized, Multicenter, Double-Blind, Placebo-Controlled Study Using Subcutaneous Dosing

Iain B. McInnes1,2, Philip J. Mease3, Bruce Kirkham4, Arthur Kavanaugh5, Christopher T. Ritchlin6, Proton Rahman7, Désirée van der Heijde8, Robert B. M. Landewé9, Philip G. Conaghan10, Hanno Richards11, Gregory Ligozio12, Luminita Pricop13 and Shephard Mpofu14, 1University of Glasgow, Glasgow, Scotland, 2University of Glasgow, Glasgow, United Kingdom, 3Swedish Medical Center and University of Washington, Seattle, WA, 4Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom, 5UC San Diego School of Medicine, La Jolla, CA, 6Allergy Immunology & Rheumatology, University of Rochester Medical Center, Rochester, NY, 7Memorial University, St John's, NF, Canada, 8Leiden University Medical Center, Leiden, Netherlands, 9University of Amsterdam and Atrium Medical Center, Amsterdam, Netherlands, 10University of Leeds, Leeds, United Kingdom, 11Clinical Immunology / Dermatology, Novartis Pharma AG, Basel, Switzerland, 12Novartis Pharmaceuticals Corporation, East Hanover, NJ, 13Integrated Hospital Care (IHC) Franchise, Novartis Pharmaceuticals Corporation, East Hanover, NJ, 14Novartis Pharma AG, Basel, Switzerland

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: , ,

Session Information

Title: ACR Late-breaking Abstracts Session

Session Type: Late-Breaking Abstracts

Background/Purpose: Secukinumab, a human anti–IL-17A monoclonal antibody, has shown efficacy in the treatment of psoriasis in phase 3 studies with subcutaneous (s.c.) dosing as well as in the treatment of psoriatic arthritis (PsA) with an intravenous loading and s.c. maintenance dose regimen (FUTURE 1; NCT01392326). We present data from FUTURE 2 (NCT01752634), the first double-blind, placebo (PBO)-controlled phase 3 study to evaluate secukinumab s.c. loading and maintenance dosing in subjects with PsA.

Methods: 397 adults with active PsA classified according to CASPAR criteria were randomized to receive s.c. secukinumab (300, 150 or 75 mg) or PBO at baseline, Week (Wk) 1, 2, 3, 4 and the respective dose every 4 wks thereafter. Subjects were stratified according to prior anti-TNF therapy; 65% of subjects were TNF-naïve and 35% were TNF-IR. The primary endpoint was ACR20 response at Wk 24. Secondary endpoints were PASI 75/90, Disease Activity Score 28 using C-reactive protein (DAS28-CRP), Short Form-36 Physical Component Summary (SF-36 PCS), Health Assessment Questionnaire-Disability Index (HAQ-DI), ACR50, dactylitis and enthesitis. Statistical analyses for primary and secondary endpoints used non-responder imputation (binary variables) or mixed-effects repeated measures modelling (continuous variables), with hierarchical testing to adjust for multiplicity.

Results: At Wk 24, ACR20 responses were significantly greater with secukinumab than PBO: 54.0%, 51.0% and 29.3% vs. 15.3%, with secukinumab 300, 150 and 75 mg vs. PBO, respectively (P < 0.0001 for secukinumab 300 and 150 mg; P < 0.05 for 75 mg vs. PBO), with improvements observed by Wk 3 for secukinumab 300 and 150 mg. Improvements in ACR50/70 responses were observed with secukinumab 300 and 150 mg (Table). Secukinumab 300 and 150 mg also improved PASI 75/90 scores (Table), DAS28-CRP, SF-36 PCS, HAQ-DI, dactylitis and enthesitis (Table) vs. PBO. Efficacy was observed with secukinumab 300 and 150 mg in both TNF-naïve and TNF-IR subgroups. Secukinumab 300 mg was associated with greater improvements than the lower doses in ACR responses, PASI 75/90 scores, SF-36 PCS, HAQ-DI, dactylitis and enthesitis in the TNF-IR group. The overall incidence of adverse events (AEs) up to Wk 16 was similar across secukinumab dose groups and placebo; 53.8% of subjects in the pooled secukinumab group and 58.2% in the PBO group reported an AE; serious AEs were reported in 3.3% and 2.0% of subjects, respectively.

Conclusion: Secukinumab 300 and 150 mg s.c. demonstrated rapid and clinically significant improvements in the signs and symptoms of active PsA. Improvements were demonstrated in TNF-IR and TNF-naïve subjects, validating the efficacy of IL-17 inhibition in this disease across the range of prior treatment history. The safety profile of secukinumab was consistent with that previously reported in subjects with PsA and psoriasis.

Table. Summary of selected 24-week efficacy results

Week 24 Data

Secukinumab 300 mg s.c.

Secukinumab 150 mg s.c.

Secukinumab 75 mg s.c.

PBO

aACR20 (% responders)

54.0*

51.0*

29.3‡

15.3

   TNF-IR (% responders)

45.5‡

29.7

14.7

14.3

  TNF-naïve (% responders)

58.2‡

63.5‡

36.9‡

15.9

aACR50 (% responders)

35.0§

35.0

18.2

7.1

ACR70 (% responders)

20.0‡

21.0‡

6.1

1.0

aPASI 75/90 (% responders)

63.4*/48.8†

48.3§/32.8§

28.0/12.0

16.3/9.3

bDactylitis (resolution of, %)

56.5‡

50.0‡

30.3

14.8

bEnthesitis (resolution of, %)

48.2‡

42.2‡

32.4

22.5

*P < 0.0001; †P < 0.001; §P < 0.01; ‡P < 0.05

aP-values adjusted for multiplicity

bData from patients with dactylitis (n = 138) and enthesitis (n = 253) at baseline.

ACR, American College of Rheumatology response criteria; PASI, Psoriasis Area and Severity Index; PBO, placebo; s.c., subcutaneous; TNF-IR, inadequate response to/intolerant of tumor necrosis factor inhibitor therapy

 

Disclosure:

I. B. McInnes,

Pfizer, UCB and BMS,

2,

Novartis, Amgen, Janssen, BMS, Pfizer, UCB, AbbVie, Celgene and Lilly,

5;

P. J. Mease,

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

2,

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

5,

AbbVie, Amgen, Biogen Idec, BMS, Crescendo, Janssen, Lilly, Pfizer, and UCB ,

8;

B. Kirkham,

AbbVie and UCB,

2,

Novartis, AbbVie, BMS, Lilly, and MSD,

5,

BMS, MSD and UCB ,

8;

A. Kavanaugh,

Novartis Pharmaceutical Corporation,

5;

C. T. Ritchlin,

Amgen and UCB,

2,

Novartis Pharmaceutical Corporation,

5;

P. Rahman,

Abbott, AbbVie, Amgen, BMS, Celgene, Janssen, Novartis, Pfizer and Roche and consultant to pharmaceutical companies dealing with biologic agents in rheumatology ,

5;

D. van der Heijde,

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,

5,

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,

2,

Director of Imaging Rheumatology BV,

6;

R. B. M. Landewé,

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

5,

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

2,

Abbott, Amgen, Bristol-Myers Squibb, Centocor, Merck, Pfizer, Roche, Schering-Plough, UCB and Wyeth,

8,

Director of Rheumatology Consultancy BV, which is a registered company under Dutch law,

6;

P. G. Conaghan,

Abbvie, Merck, Roche, Pfizer, Novartis and UCB,

5;

H. Richards,

Novartis Pharma AG,

3;

G. Ligozio,

Novartis Pharmaceuticals Corporation,

1,

Novartis Pharmaceuticals Corporation,

3;

L. Pricop,

Novartis Pharmaceuticals Corporation,

1,

Novartis Pharmaceuticals Corporation,

3;

S. Mpofu,

Novartis Pharma AG,

1,

Novartis Pharma AG,

3.

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