Responsiveness of serum C‐reactive protein, interleukin‐17A, and interleukin‐17F levels to ustekinumab in psoriatic arthritis: lessons from two phase III, multicenter, double‐blind, placebo‐controlled trials

Siebert, S. , Sweet, K., Dasgupta, B., Campbell, K., McInnes, I. B. and Loza, M. J. (2019) Responsiveness of serum C‐reactive protein, interleukin‐17A, and interleukin‐17F levels to ustekinumab in psoriatic arthritis: lessons from two phase III, multicenter, double‐blind, placebo‐controlled trials. Arthritis and Rheumatology, 71(10), pp. 1660-1669. (doi:10.1002/art.40921) (PMID:31070869)

[img] Text
187066.pdf - Accepted Version
Restricted to Repository staff only until 9 May 2020.

1MB

Abstract

Objective: To evaluate the associations of C‐reactive protein (CRP) and circulating Th17‐associated cytokine levels with psoriatic arthritis (PsA) disease activity and therapeutic response to ustekinumab. Methods: Interleukin‐17A (IL‐17A), IL‐17F, IL‐23, and CRP concentrations were measured in serum samples collected as part of the 2 PSUMMIT phase III studies of ustekinumab in PsA (n = 927). In post hoc analyses, relationships of IL‐17A, IL‐17F, and CRP levels at baseline, week 4, and week 24 with baseline skin and joint disease activity and response to therapy were evaluated using generalized linear models and Pearson's product‐moment correlation tests. Results: Baseline serum levels of IL‐17A and IL‐17F were positively correlated with baseline skin disease scores (r = 0.39–0.62). IL‐23 levels were correlated with skin disease scores to a lesser extent (r = 0.26–0.31). No significant correlations were observed between these cytokine or CRP levels and baseline joint disease activity. There was no significant association of baseline levels of IL‐17A, IL‐17F, IL‐23, or CRP with therapeutic response to ustekinumab in either the skin or joints. Significant reductions from baseline in levels of IL‐17A, IL‐17F, and CRP were seen in patients treated with ustekinumab compared to those treated with placebo. Ustekinumab‐treated patients in whom 75% improvement in the Psoriasis Area and Severity Index score or 20% improvement according to the American College of Rheumatology criteria was achieved after 24 weeks of treatment had greater reductions in CRP level (geometric mean decreases of 51–58% versus 32–33%; P < 0.05), but not IL‐17A or IL‐17F levels, than nonresponders. Conclusion: Baseline serum IL‐23/IL‐17 levels correlated with skin, but not joint, disease activity, suggesting tissue‐specific variation. However, neither baseline Th17‐associated cytokine levels nor CRP level were predictive of therapeutic response to ustekinumab in the skin or joints, despite rapid reductions in their levels following ustekinumab therapy.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Siebert, Dr Stefan
Authors: Siebert, S., Sweet, K., Dasgupta, B., Campbell, K., McInnes, I. B., and Loza, M. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Arthritis and Rheumatology
Publisher:Wiley
ISSN:2326-5191
ISSN (Online):2326-5205
Published Online:09 May 2019
Copyright Holders:Copyright © 2019 American College of Rheumatology
First Published:First published in Arthritis and Rheumatology 71(10):1660-1669
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

University Staff: Request a correction | Enlighten Editors: Update this record

Downloads per month over past year

View more statistics