SAT0321 Ixekizumab treatment significantly improves enthesitis and dactylitis in patients with active psoriatic arthritis: results from the spirit trials
Authors: D.D. Gladman, A.-M. Orbai, G. Gallo, J. Birt, S. Rathmann, H. Marzo-Ortega
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Psoriatic arthritis (PsA) is a chronic inflammatory disease with heterogeneous musculoskeletal manifestations including enthesitis and dactylitis. Ixekizumab (IXE), an interleukin-17A antagonist, is approved in the USA for the treatment of PsA including patients with pre-existing enthesitis or dactylitis. <h3>Objectives</h3> To investigate the impact of IXE treatment on the resolution of enthesitis or dactylitis and whether such improvements were associated with improved function and health-related quality of life (HRQoL). <h3>Methods</h3> Patients with active PsA who were biologic-naïve (SPIRIT-P1; NCT01695239) or with prior inadequate response to tumour necrosis factor inhibitor(s) (SPIRIT-P2; NCT02349295) were randomised to placebo (PBO) or 80 mg IXE every 4 weeks (IXEQ4W) or 2 weeks (IXEQ2W), after a 160 mg starting dose. All patients who were inadequate responders at Week 16 received rescue therapy (changes in background therapy). Leeds Enthesitis Index (LEI), Leeds Dactylitis Index-Basic (LDI-B), Health Assessment Questionnaire Disability Index (HAQ-DI), and EuroQoL-5D Visual Analogue Scale (EQ-5D VAS) were measured at Week 24. Missing data or data from inadequate responders were considered non-response or imputed with last observation carried forward for categorical and continuous measures, respectively. Statistical comparisons between PBO and IXE treatment groups were performed with a logistic regression model using Wald's test with treatment and study as factors. In post hoc-analyses, associations between enthesitis and dactylitis with HAQ-DI and EQ-5D VAS are based on an ANCOVA model adjusting for study and Disease Activity of Psoriatic Arthritis (DAPSA). <h3>Results</h3> In the integrated SPIRIT-P1 and -P2 dataset (n=679), 403 patients (59% of total) had baseline enthesitis (LEI &gt;0) with a mean 2.9 LEI score, and 155 patients (23% of total) had baseline dactylitis (LDI-B &gt;0) with a mean 56.4 LDI-B score. Relative to PBO, IXE treatment resulted in significantly higher resolution of enthesitis (SPIRIT-P1) and dactylitis (SPIRIT-P1 and -P2) after 24 weeks.<sup>1,2</sup> In the integrated SPIRIT-P1 and –P2 dataset, both IXEQ4W and IXEQ2W had significantly higher enthesitis and dactylitis resolution than PBO treatment at Week 24 (Table). In ad-hoc analysis, IXE treatment had significantly higher resolution of enthesitis compared to PBO at the entheseal points comprising the LEI score (Table). For all PBO- and IXE-treated patients at Week 24, least squares mean (SE) HAQ-DI changes from baseline were −0.44 (0.05) and −0.25 (0.03; p&lt;0.01) for patients who did and did not resolve enthesitis, and −0.41 (0.06) and −0.31 (0.07; p=0.34) for patients who did and did not resolve dactylitis. Corresponding EQ-5D VAS improvements were 12.3 (2.2) and 5.8 (1.5; p=0.02) for patients who did and did not resolve enthesitis, and 10.8 (2.8) and 9.8 (3.5; p=0.83) for patients who did and did not resolve dactylitis. <h3>Conclusions</h3> Treatment with IXE resulted in significant improvement in enthesitis and dactylitis in patients with pre-existing enthesitis or dactylitis. Resolution of enthesitis symptoms was associated with improvements in patients' function and HRQoL. <h3>References</h3> [1] Mease, et al. ARD2017;76(1):79. [2] Nash, et al. Lancet2017;389(10085):2317. <h3>Disclosure of Interest</h3> D. Gladman Grant/research support from: Abbvie, Amgen, Celgene, Janssen, Novartis, Pfizer, UCB, Consultant for: Abbvie, Amgen, BMS, Celgene, Eli Lilly and Company, Janssen, Novartis, Pfizer, UCB, A.-M. Orbai Grant/research support from: Abbvie, Celgene, Eli Lilly, Horizon, Janssen, Novartis, Pfizer, Consultant for: Eli Lilly, Janssen, Novartis, Pfizer, UCB, G. Gallo Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, J. Birt Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, S. Rathmann Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, H. Marzo-Ortega Grant/research support from: Janssen, Speakers bureau: Abbvie, Celgene, Janssen, MSD, Novartis, Pfizer and UCB