Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose
Reducing the burden of skin manifestations of psoriatic arthritis (PsA) is an important aspect of disease management. Secukinumab, a human anti–IL-17A monoclonal antibody, has demonstrated rapid and sustained efficacy in the treatment of psoriasis in phase 3 trials, including in the subset of patients (pts) with PsA. Here we present the effect of secukinumab on dermatological parameters in pts enrolled in FUTURE 1 (NCT01392326), the first phase 3 trial to evaluate the efficacy of IL-17A inhibition in pts with PsA.
Methods
Adults with moderate to severe PsA according to ClASsification of Psoriatic ARthritis criteria were randomized to a secukinumab 10 mg/kg intravenous (i.v.) loading dose at baseline (BL), Week (Wk) 2, and Wk 4, then either 75 mg subcutaneously (s.c.; 10 IV→75 SC) or 150 mg s.c. (10 IV→150 SC) every 4 wks from Wk 8, or placebo (PBO) on the same i.v. and s.c. schedules. Assessments of psoriasis burden included 75% and 90% improvement in Psoriasis Area and Severity Index (PASI 75/90), Investigator’s Global Assessment (modified 2011) score of 0 or 1 (IGA 0/1), target lesion score (TLS), modified Nail Psoriasis Severity Index (mNAPSI), and the Dermatology Life Quality Index (DLQI). The effect of treatment on high-sensitivity C-reactive protein (hsCRP) levels, a marker of skin and joint inflammation, was also monitored.
Results
From the full analysis set (FAS) of 606 pts, 325 (53.6%) had psoriasis affecting ≥ 3% of body surface area at BL (psoriasis subset), 510 (84.2%) had a psoriatic target lesion ≥ 2 cm in diameter (TLS subset) and 435 (71.8%) had nail involvement (nail subset). Improvements in dermatology parameters with secukinumab vs. PBO at Wk 24 are presented in the table. In the psoriasis subset, 10 IV→75 SC and 10 IV→150 SC significantly improved the proportion of PASI 75, PASI 90, and IGA 0/1 responders vs. PBO at Wk 24, and provided clinically meaningful improvement (≥ 4-point change from BL) in DLQI, with most pts having a decline in DLQI score from > 10 (severe) at BL to < 4 at Wk 24. Pts in the TLS subset experienced a rapid (from Wk 1) and significant improvement in TLS with secukinumab vs. PBO at Wk 24, while mNAPSI was significantly improved with secukinumab in the nail subset. hsCRP values were significantly lower with secukinumab vs. PBO from Wk 1 through Wk 24 (FAS).The improvements in dermatological parameters observed with secukinumab at Wk 24 were sustained through Wk 52.
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Table. Effect of treatment on skin and involvement at Week 24 |
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BL and Wk 24 Data |
Secukinumab 10 mg/kg IV → 75 mg SC |
Secukinumab 10 mg/kg IV → 150 mg SC |
Placebo |
|
aPASI Responses BL score PASI 75/90, % responders |
6.4 64.8* / 49.1* |
9.2 61.1* / 45.4* |
8.9 8.3 / 3.7 |
|
aIGA 0/1, % responders |
54.6* |
49.1* |
3.7 |
|
bTLS BL Mean change from BL |
5.5 –4.46* |
6.0 –4.64* |
6.1 –1.31 |
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cmNAPSI BL Mean change from BL |
18.6 –12.3* |
18.7 –10.9* |
17.5 –4.1 |
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aDLQI total score BL Mean change from BL |
11.2 –7.87* |
12.6 –8.80* |
12.5 0.70 |
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*P < 0.0001 vs. placebo; aData from patients with psoriasis affecting ≥ 3% of body surface area at BL (n=325); bTLS data from patients with psoriatic target lesion ≥ 2 cm in diameter (n=510); cData from patients with nail psoriasis (n=435). BL, baseline; DLQI, Dermatology Life Quality Index;IGA, Investigator’s Global Assessment; IV, intravenous; mNAPSI, modified Nail Psoriasis Severity Index; PASI, Psoriasis Area and Severity Index; SC, subcutaneous; TLS, target lesion score |
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Conclusion
This is the first phase 3 trial in pts with active PsA to demonstrate that selective IL-17A inhibition with secukinumab significantly reduces the severity of plaque and nail psoriasis and improves quality of life in those pts with a significant concomitant psoriasis burden in addition to their joint disease.
Disclosure:
A. B. Gottlieb,
Consulting fees from 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,,
5,
Advisory Board Agreements: 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, ,
9,
Research/Educational Grants (paid to Tufts Medical Center): Centocor (Janssen), Amgen, Abbott (Abbvie), Novartis, Celgene, Pfizer, Lilly, Coronado, Levia, Merck,
2;
P. J. Mease,
Research grants from AbbVie, Amgen, Biogen Idec, BMS, Celgene, Crescendo, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, and Vertex,
2,
Consulting fees from: AbbVie, Amgen, Biogen Idec, BMS, Celgene, Covagen, Crescendo, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, and Vertex,
5,
Speakers’ bureau for AbbVie, Amgen, Biogen Idec, BMS, Crescendo, Janssen, Lilly, Pfizer, and UCB ,
8;
I. B. McInnes,
Consulting fees from Novartis, Amgen, Janssen, BMS, Pfizer, UCB, Abbvie, Celgene and Lilly,
5;
B. Kirkham,
Research grants from AbbVie and UCB,
2,
Consulting fees from Novartis, AbbVie, BMS, Lilly, and MSD,
5,
Speakers’ bureau for BMS, MSD, and UCB ,
8;
A. Kavanaugh,
Consulting fees from Novartis,
5;
P. Rahman,
Consulting fees from Abbott, AbbVie, Amgen, BMS, Celgene, Janssen, Novartis, Pfizer and Roche,
5;
P. Nash,
from Novartis, Abbvie, Roche, Pfizer, BMS, Janssen, and Celgene,
2,
Honoraria for lectures and advice from Novartis, Abbvie, Roche, Pfizer, BMS, Janssen, and Celgene,
9;
L. Pricop,
Employee of Novartis ,
3,
Novartis stock ,
1;
J. Yuan,
Employee of Novartis ,
3;
H. Richards,
Employee of Novartis ,
3;
S. Mpofu,
Novartis stock ,
1,
Employee of Novartis ,
3.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/secukinumab-a-human-anti-interleukin-17a-monoclonal-antibody-significantly-reduces-psoriasis-burden-in-patients-with-psoriatic-arthritis-results-from-a-phase-3-randomized-controlled-trial/