Background/Purpose: Enthesitis is a key feature of all types of spondyloarthritis (SpA) that substantially contributes to the overall burden of disease. Inhibition of the key effector cytokines of enthesitis, IL‑17, IL‑23, and TNF, has proved effective in resolution of PsA and axial (ax)SpA.¹ Secukinumab (SEC) is a fully human monoclonal antibody that directly inhibits IL-17A and significantly reduces entheseal inflammation in patients (pts) with PsA.² The clinical efficacy and safety outcomes from the ACHILLES trial in a heterogeneous SpA population (PsA and axSpA pts) with enthesitis at the Achilles tendon treated with SEC are presented.

Methods: ACHILLES study included pts (≥18 years) with a diagnosis of active PsA (CASPAR criteria and ≥1 TJC and SJC) or axSpA (ASAS axSpA criteria and total BASDAI ≥4) and MRI-positive heel enthesitis (according to the investigator’s judgement) refractory to standard treatment. Pts were randomized to receive s.c. SEC 150 mg, 300 mg or placebo (PBO) at baseline, Weeks (Wks) 1, 2, 3 and 4, followed by once every 4 wks. At Wk 24, pts on PBO were switched to SEC 150 or 300 mg. The primary endpoint was the proportion of pts achieving resolution of Achilles tendon enthesitis at the affected foot (assessed by the respective subcomponent of Leeds Enthesitis Index, LEI) with SEC vs PBO at Wk 24. Assessments at Wks 24 and 52 included LEI, heel pain (by NRS [0-10]), physician’s and pt’s heel enthesopathy activity and global assessment of disease activities (by VAS [0–100]), and quality of life (QoL, SF-36 v2). Analysis comparing treatments with respect to the primary efficacy variable used a logistic regression model and continuous variables were analyzed using an Analysis of covariance model. Missing values were handled using mixed-effects model repeated measures and last observation carry forward method.

Results: A total of 204 pts (128 PsA, 76 axSpA) were included (SEC, N=102; PBO, N=102; Table 1). A numerically higher percentage of SEC-treated pts, though not statistically significant vs PBO, reported resolution of Achilles tendon enthesitis at the affected foot (42.2% vs 31.4%) and in LEI (33.3% vs 23.5%) at Wk 24 (Table 2); statistically significant LEI improvement was achieved in PsA pts treated with SEC vs PBO (35.9% vs 18.8%, p=0.025). Pts with a BMI < 30 kg/m² improved considerably with SEC vs PBO (49.2% vs 24.6%). Heel pain significantly improved in SEC-treated pts vs PBO (Table 2). Significant improvements in physician and pt reported heel enthesopathy activity along with physician and pt global assessment of disease activity were observed in SEC-treated pts vs PBO. SEC provided sustained improvements in all efficacy endpoints through Wk 52. The safety profile of SEC was consistent with previous studies.

Conclusion: Although SEC was not significantly superior to PBO in the resolution of Achilles tendon enthesitis as assessed by the LEI subcomponent at the affected foot, it significantly improved the burden of heel enthesitis, global disease activity, and QoL in pts with active SpA refractory to standard treatment.

References:

1. Schett G, et al. Nat Rev Rheumatol. 2017;13:731–741.
2. Coates LC, et al. Arthritis Res Ther. 2019;21:266.

Table 1: Demographics and Baseline Characteristics

Table 2: Clinical Efficacy Endpoints up to Week 52

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-and-safety-of-secukinumab-in-patients-with-spondyloarthritis-and-enthesitis-at-the-achilles-tendon-52-weeks-results-from-a-randomized-placebo-controlled-phase-3b-trial/