Background/Purpose: Ixekizumab (IXE), an IL-17A antagonist, is approved in the USA for the treatment of PsA including patients (pts) with pre-existing enthesitis or dactylitis. Previous results have shown significantly higher resolution of enthesitis (SPIRIT-P1) and dactylitis (SPIRIT-P1 and -P2) after 24 wks.^1,2 The purpose of the study was 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: Pts with active PsA who were biologic-naïve (SPIRIT-P1)¹ or with prior inadequate response to tumor necrosis factor inhibitor(s) (SPIRIT-P2)² were randomized to placebo (PBO) or 80-mg IXE every 4 (IXEQ4W) or 2 weeks (wks; IXEQ2W), after a 160-mg starting dose. At Wk 16, all inadequate responders received rescue therapy (changes in background therapy). Leeds Enthesitis Index (LEI), Leeds Dactylitis Index-Basic (LDI-B), HAQ Disability Index (HAQ-DI), and EuroQoL-5D Visual Analog Scale (EQ-5D VAS) were measured at Wk 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 PsA (DAPSA).

Results: In the integrated SPIRIT-P1 and -P2 dataset (N=679), 403 pts (59% of total) had baseline enthesitis (LEI>0) with a mean 2.9 LEI score, and 155 pts (23% of total) had baseline dactylitis (LDI-B>0) with a mean 56.4 LDI-B score. Both IXEQ4W and IXEQ2W had significantly higher enthesitis and dactylitis resolution than PBO at Wk 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 pts at Wk 24, least squares mean (SE) HAQ-DI improvement from baseline were -0.44 (0.05) and -0.25 (0.03; p<0.01) for pts who did and did not resolve enthesitis, and -0.41 (0.06)  and -0.31 (0.07; p=0.34) for pts 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 pts who did and did not resolve enthesitis, and 10.8 (2.8) and 9.8 (3.5; p=0.83) for pts who did and did not resolve dactylitis.

Conclusion: Treatment with IXE resulted in significant improvement in enthesitis and dactylitis in pts with pre-existing enthesitis or dactylitis. Resolution of enthesitis symptoms was associated with improvements in pts’ function and HRQoL.

References

1. Mease et al. 2017 ARD 76(1):79

2. Nash et al. 2017 Lancet 389(10085):2317