Ixekizumab treatment significantly improves enthesitis and dactylitis in patients with active psoriatic arthritis: Results from the spirit trials

Background: 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. Objectives: 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). Methods: 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 (HAQDI), and EuroQoL-5D Visual Analogue Scale (EQ-5D VAS) were measured at Week 24. Missing data or data from inadequate responders were considered nonresponse 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). Results: In the integrated SPIRIT-P1 and -P2 dataset (n=679), 403 patients (59% of total) had baseline enthesitis (LEI >0) with a mean 2.9 LEI score, and 155 patients (23% of total) had baseline dactylitis (LDI-B >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.1,2 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<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. Conclusions: 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 (Table Presented).