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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
Author(s) -
Siebert Stefan,
Sweet Kristen,
Dasgupta Bidisha,
Campbell Kim,
McInnes Iain B.,
Loza Matthew J.
Publication year - 2019
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.40921
Subject(s) - ustekinumab , medicine , psoriatic arthritis , c reactive protein , psoriasis area and severity index , interleukin 17 , post hoc analysis , interleukin 23 , psoriasis , placebo , gastroenterology , interleukin , vitamin d and neurology , randomization , cytokine , rheumatology , arthritis , immunology , clinical trial , disease , pathology , inflammation , adalimumab , alternative medicine
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.