SAT0344 The effect of guselkumab on enthesitis: results from a phase 2 study in patients with active psoriatic arthritis
Authors: P. Helliwell, A.B. Gottlieb, A. Deodhar, W.-H. Boehncke, D. McGonagle, X.L. Xu, S. Xu, Y. Wang, E.C. Hsia, C.S. Karyekar, P. Mease
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> In a Phase 2 study, Guselkumab (GUS) was shown to be safe and effective in patients (pts) w/active psoriatic arthritis (PsA) w/meaningful improvements in enthesitis. <h3>Objectives</h3> To evaluate the effect of GUS on enthesitis in a subset of pts w/enthesitis at baseline (BL) from the phase 2 PsA study of GUS. <h3>Methods</h3> Pts w/active PsA and ≥3% body surface area of plaque psoriasis, despite current or previous treatment, were randomised 2:1 to receive 100 mg subcutaneous GUS or placebo (PBO) at weeks (wks) 0, 4, then every 8 wks (q8w) during a 24-wk double-blind treatment period. At wk16, pts w/&lt;5% improvement in swollen and tender joint counts early escaped (EE) to open-label ustekinumab. At wk24, the PBO group crossed over to receive GUS at wks 24, 28 then q8w(PBO→GUS) and the GUS group continued receiving GUS (GUS→GUS)) through wk44. Enthesitis was assessed using the Leeds enthesitis index (LEI). Enthesitis scores during the 24-wk double-blind treatment was analysed using LOCF imputation for missing data and EE. Enthesitis after wk24 was analysed using observed data. <h3>Results</h3> Of 149 total pts w/active PsA, 107 (72%) presented w/enthesitis at BL (PBO n=31, mean [SD] LEI=2.6 [1.48], median [range]=2.0;<sup>1, 6</sup> GUS n=76, mean (SD) LEI=2.7 [1.54], median [range]=2.0<sup>1, 6</sup>) and 85 continued at Wk24 (PBO→GUS n=18; GUS→GUS n=67). Except for higher tender/swollen joint counts and CRP, BL characteristics of the enthesitis subset was similar to the overall population. GUS significantly reduced the LEI by wk8 (mean [SD] change from baseline, PBO: −0.4 [1.59]; GUS: −1.2 [1.65]; p=0.037), and through wk24 (mean [SD] change from baseline, PBO: −0.7 [1.53]; GUS: −1.5 [1.81]; p=0.045). GUS also significantly increased the% of pts w/enthesitis resolution (figure 1). After wk24, the PBO→GUS group achieved rapid, sustained resolution (wk56: mean[SD] change from BL=−2.1 [1.65]; 62.5% of pts w/resolution), similar to GUS→GUS group (wk56: mean[SD] change from BL=−1.9 [1.59], 70.8% of pts w/resolution). Improvement in enthesitis was observed at each enthesitis site assessed, and was greater in ACR20 (Table) responders vs non-responders in GUS-treated patients and was correlated w/improvement in tender (R=0.37, p=0.001) and swollen (R=0.27, p=0.020) joint counts, physician's (R=0.47, p&lt;0.0001) and patient's global assessment of disease activity (R=0.32, p=0.005), and SF36 PCS (R=0.27, p=0.02) and MCS (R=0.35, p=0.002). <h3>Conclusions</h3> GUS treatment produces rapid and sustained improvement of enthesitis in pts w/active PsA, which correlates w/improvement in joint symptoms and patient-reported outcomes. <h3>Disclosure of Interest</h3> P. Helliwell Grant/research support from: Janssen Research and Development, LLC, A. Gottlieb Grant/research support from: Janssen Research and Development, LLC, A. Deodhar Grant/research support from: Janssen Research and Development, LLC, W.-H. Boehncke Grant/research support from: Janssen Research and Development, LLC, D. McGonagle Grant/research support from: Janssen Research and Development, LLC, X. Xu Employee of: Johnson and Johnson, S. Xu Employee of: Johnson and Johnson, Y. Wang Employee of: Johnson and Johnson, E. Hsia Employee of: Johnson and Johnson, C. Karyekar Employee of: Johnson and Johnson, P. Mease Grant/research support from: Janssen Research and Development, LLC