Secukinumab inhibition of interleukin-17A in patients with psoriatic arthritis

Mease, Philip J., McInnes, Iain B., Kirkham, Bruce, Kavanaugh, Arthur, Rahman, Proton, Van Der Heijde, Desiree, Landewe, Robert, Nash, Peter, Pricop, Luminita, Yuan, Jiacheng, Richards, Hanno B. and Mpofu, Shephard (2015) Secukinumab inhibition of interleukin-17A in patients with psoriatic arthritis. New England Journal of Medicine, 373 14: 1329-1339. doi:10.1056/NEJMoa1412679


Author Mease, Philip J.
McInnes, Iain B.
Kirkham, Bruce
Kavanaugh, Arthur
Rahman, Proton
Van Der Heijde, Desiree
Landewe, Robert
Nash, Peter
Pricop, Luminita
Yuan, Jiacheng
Richards, Hanno B.
Mpofu, Shephard
Title Secukinumab inhibition of interleukin-17A in patients with psoriatic arthritis
Journal name New England Journal of Medicine   Check publisher's open access policy
ISSN 1533-4406
0028-4793
Publication date 2015-10-01
Year available 2015
Sub-type Article (original research)
DOI 10.1056/NEJMoa1412679
Open Access Status Not Open Access
Volume 373
Issue 14
Start page 1329
End page 1339
Total pages 11
Place of publication Waltham, Massachusetts, United States
Publisher Massachussetts Medical Society
Collection year 2016
Language eng
Formatted abstract
BACKGROUND
In a phase 2 study, the inhibition of the interleukin-17A receptor improved signs and symptoms of psoriatic arthritis. We sought to evaluate the efficacy and safety of secukinumab, an anti–interleukin-17A monoclonal antibody, in such patients.

METHODS

In this double-blind, phase 3 study, 606 patients with psoriatic arthritis were randomly assigned in a 1:1:1 ratio to receive intravenous secukinumab (at a dose of 10 mg per kilogram) at weeks 0, 2, and 4, followed by subcutaneous secukinumab at a dose of either 150 mg or 75 mg every 4 weeks, or placebo. Patients in the placebo group were switched to subcutaneous secukinumab at a dose of 150 mg or 75 mg at week 16 or 24, depending on clinical response. The primary end point was the proportion of patients with an American College of Rheumatology 20 (ACR20) response at week 24, defined as a 20% improvement from baseline in the number of tender and swollen joints and at least three other important domains.

RESULTS
ACR20 response rates at week 24 were significantly higher in the group receiving secukinumab at doses of 150 mg (50.0%) and 75 mg (50.5%) than in those receiving placebo (17.3%) (P<0.001 for both comparisons with placebo). Secondary end points, including the ACR50 response and joint structural damage, were significantly better in the secukinumab groups than in the placebo group. Improvements were sustained through 52 weeks. Infections, including candida, were more common in the secukinumab groups. Throughout the study (mean secukinumab exposure, 438.5 days; mean placebo exposure, 128.5 days), four patients in the secukinumab groups had a stroke (0.6 per 100 patient-years; 95% confidence interval [CI], 0.2 to 1.5), and two had a myocardial infarction (0.3 per 100 patient-years; 95% CI, 0.0 to 1.0), as compared with no patients in the placebo group.

Conclusions
Secukinumab was more effective than placebo in patients with psoriatic arthritis, which validates interleukin-17A as a therapeutic target. Infections were more common in the secukinumab groups than in the placebo group. The study was neither large enough nor long enough to evaluate uncommon serious adverse events or the risks associated with long-term use.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
 
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