ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 952

A Phase IIb, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Multicenter Study to Evaluate the Efficacy and Safety of Clazakizumab, an Anti-IL-6 Monoclonal Antibody, in Adults with Active Psoriatic Arthritis

Philip J. Mease1, A B Gottlieb2, A Berman3, E Drescher4, J Xing5, S Banerjee5 and R Wong5, 1Swedish Medical Center and University of Washington, Seattle, WA, 2Tufts Medical Center and Tufts University School of Medicine, Boston, MA, 3Centro Médico Privado de Reumatología, Tucuman, Argentina, 4Csolnoky Ferenc Hospital, Veszprém, Hungary, 5Bristol-Myers Squibb, Princeton, NJ

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: ,

Session Information

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

Session Type: Abstract Submissions (ACR)

Background/Purpose: New treatment options for psoriatic arthritis (PsA) are needed and interleukin-6 (IL-6), a cytokine with a central role in chronic inflammation, is a potential therapeutic target. This Phase IIb study evaluated the efficacy of 3 doses of SC clazakizumab (CLZ) – a potent, selective antibody to the IL-6 cytokine – with or without MTX versus placebo (PBO) in patients (pts) with PsA. Methods: Pts with PsA according to the Classification Criteria for Psoriatic Arthritis (CASPAR) and active disease, who had an inadequate response to NSAIDs and/or DMARDs, were randomized to 1 of 4 treatment arms: CLZ 25, 100, or 200 mg, or PBO, with or without MTX, every 4 wks for 24 wks. The primary endpoint was ACR20 response rate at Wk 16. Additional secondary endpoints evaluated at Wk 24 include ACR20/50/70 and Psoriasis Area and Severity Index 75 (PASI75) response rates; changes in HAQ-DI and DAS28 (CRP); and dactylitis and enthesitis scores. All pts who discontinued or received rescue treatment prior to Wk 16 were imputed as non-responders at the Wk 16 analysis and all subsequent visits. Results: A total of 165 pts were treated and analyzed. Baseline characteristics were balanced, including use of background MTX in ~70% of pts, except mean body weight (approximately 8 kg lower in PBO and CLZ 25 mg arms) and disease duration (3–5 yrs less in CLZ 100 and 200 mg arms). The study primary endpoint was met, with ACR20 response rates significantly higher in the CLZ 100 mg arm vs PBO (52.4 vs 29.3%, p=0.039) and numerically higher in the CLZ 25 and 200 mg arms (46.3 [p=0.101] and 39.0% [p=0.178], respectively) at Wk 16. The table shows secondary endpoints. ACR20/50/70 response rates were higher than PBO for all CLZ treatment arms at Wk 24, but no clear dose response was seen. Mean decreases from baseline to Wk 24 in DAS28 (CRP), HAQ-DI, the number of dactylitic digits and Spondyloarthritis Research Consortium of Canada (SPARCC) enthesitis score were greater in all CLZ treatment arms compared with PBO. PASI75 response rates were 12.2% in the PBO arm and between 12.2 and 28.6% in the CLZ arms at Wk 24. Through Wk 24, the rates of serious adverse events (SAEs) were similar across PBO, CLZ 25 and CLZ 100 mg arms (4.9, 4.9 and 4.8%, respectively) and higher for the CLZ 200 mg arm (9.8%), which was associated with more discontinuations. No serious infections, tuberculosis, malignancies, gastrointestinal perforations or unusual SAEs, were observed during the study period. Consistent with IL-6 blockade, non-clinically significant liver enzyme elevations and reductions in platelet and neutrophil counts were observed in the 3 CLZ treatment arms.

Week 24 results PBO
(n=41) 		CLZ 25 mg
(n=41) 		CLZ 100 mg
(n=42) 		CLZ 200 mg
(n=41)
ACR20, % (95% CI) 34.1 (19.6, 48.7) 56.1 (40.9, 71.3) 57.1 (42.2, 72.1) 39.0 (24.1, 54.0)
ACR50, % (95% CI) 14.6 (3.8, 25.5) 34.1 (19.6, 48.7) 35.7 (21.2, 50.2) 24.4 (11.2, 37.5)
ACR70, % (95% CI) 4.9 (0.6, 16.5) 19.5 (7.4, 31.6) 23.8 (10.9, 36.7) 12.2 (2.2, 22.2)
DAS28 (CRP), mean CFB (95% CI) % CFB* –0.93
(–1.31, –0.55)
–18.6 		–2.26
(–2.65, –1.88)
–43.7 		–2.25
(–2.62, –1.87)
–43.9 		–2.16
(–2.55, –1.76)
–44.3
HAQ-DI, mean CFB
(95% CI) % CFB* 		–0.26
(–0.43, –0.09)
–19.0 		–0.46
(–0.63, –0.29)
–31.7 		–0.43
(–0.59, –0.26)
–32.1 		–0.34
(–0.52, –0.17)
–25.0
SPARCC, mean CFB (95% CI) % CFB* –1.3
(–2.4, –0.3)
–22.8 		–3.6 (–4.6, –2.6)
–72.0 		–2.7
(–3.7, –1.7)
–60.0 		–2.5
(–3.7, –1.4)
–59.5
LEI, mean CFB (95% CI) % CFB* –1.1
(–1.5, –0.7)
–44.0 		–1.3
(–1.6, –0.9)
–72.2 		–1.4
(–1.8, –1.1)
–77.8 		–1.1
(–1.5, –0.7)
–61.1
Mean no. dactylitic digits in pts with dactylitis at baseline (SD) % CFB* 2.5
(3.78)

+4.2

1.4
(2.1)

–51.7

0.2
(0.4)

–90.0

0.8
(1.53)

–68.0

PASI75, %
(95% CI) 		12.2
(2.2, 22.2) 		19.5
(7.4, 31.6) 		28.6
(14.9, 42.2) 		12.2
(2.2, 22.2)
CFB=change from baseline; LEI=Leeds Enthesitis Index *Calculated based on mean values at baseline and Week 24.

  Conclusion: Clazakizumab is effective in controlling clinical features of PsA such as arthritis, enthesitis and dactylitis, with modest skin benefits. The safety profile was acceptable and consistent with IL-6 blockade. This is the first demonstration of a beneficial effect of targeting IL-6 in PsA and further studies are warranted.

Disclosure:

P. J. Mease,

AbbVie, Amgen, Biogen Idec, Bristol-Myers Squibb, Celgene, Crescendo, Genentech, Jansses, Lilly, Merck, Novartis, Pfizer, UCB, Vertex,

2,

AbbVie, Amgen, Biogen Idec, Bristol-Myers Squibb, Celgene, Covagen, Crescendo, Genentech, Jansses, Lilly, Merck, Novartis, Pfizer, UCB, Vertex,

5,

AbbVie, Amgen, Biogen Idec, Bristol-Myers Squibb, Crescendo, Genentech, Jansses, Lilly, Pfizer, UCB,

8;

A. B. Gottlieb,

Amgen, Astellas, Akros, Centocor (Janssen), Celgene, Bristol-Myers Squibb, Beiersdorf, Abbott Labs (AbbVie), Teva, Actelion, UCB, Novo Nordisk, Novartis, Dermipsor, Incyte, Pfizer, Canfite, Lilly, Coronado, Vertex, Karyopharm, CSL Behring Biotherapies for,

5,

Centocor (Janssen), Amgen, Abbott (Abbvie), Novartis, Celgene, Pfizer, Lilly, Coronado, Levia, Merck,

2;

A. Berman,
None;

E. Drescher,
None;

J. Xing,

Bristol-Myers Squibb,

3;

S. Banerjee,

Bristol-Myers Squibb,

1,

Bristol-Myers Squibb,

3;

R. Wong,

Bristol-Myers Squibb,

1,

Bristol-Myers Squibb,

3.

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