Efficacy and safety of secukinumab in patients with spondyloarthritis and enthesitis at the Achilles tendon: results from a phase 3b trial

Abstract

Objective ACHILLES aimed to demonstrate efficacy of secukinumab on Achilles’ tendon enthesitis in spondyloarthritis (SpA) patients. Methods Patients ≥18 years (n = 204) with active PsA or axial SpA and heel enthesitis were randomized 1:1 to secukinumab 150/300 mg or placebo up to week 24, and thereafter placebo patients were switched to secukinumab. Results At week 24, a higher, yet statistically non-significant (P = 0.136), proportion of patients in secukinumab vs placebo reported resolution of Achilles tendon enthesitis in affected foot (42.2% vs 31.4%; odds ratio [OR] = 1.63; 95% CI: 0.87, 3.08). Proportion of patients reporting resolution of enthesitis based on Leeds Enthesitis Index was higher with secukinumab vs placebo (33.3% vs 23.5%; OR = 1.65; 95% CI: 0.85, 3.25) at week 24. Mean change from baseline in heel pain at week 24 was higher in secukinumab patients vs placebo (−2.8 [3.0] vs −1.9 [2.7]). Greater improvements with secukinumab were observed in heel enthesopathy activity and global assessment of disease activity. Imaging evaluation by local reading confirmed heel enthesitis on MRI at screening for all patients. Based on central reading, 56% presented with bone marrow oedema and/or tendinitis; according to Heel Enthesitis MRI Scoring System (HEMRIS) post hoc analysis, 76% had signs of entheseal inflammation while 86% had entheseal inflammation and/or structural changes. Conclusion A substantial proportion of patients showed no signs of inflammation on the centrally read MRIs despite a clinical diagnosis of heel enthesitis, thus highlighting that the discrepancy between the clinical and imaging assessments of enthesitis requires further investigation. Although ACHILLES did not meet the primary end point, the study reported clinically meaningful improvements in patient-related outcomes. Trial registration clinicaltrials.gov, NCT02771210

Clinical efficacy of JAK inhibitors on enthesitis in spondyloarthropathy: A scoping literature review

“…There are studies demonstrating the effect of biologic DMARDs on peripheral enthesitis imaging in patients with PsA and AxSpA, including ultrasound (Aydin et al., 2010; Hu et al., 2015; Narcisi et al., 2022; Wang et al., 2015) and MRI (Althoff et al., 2016; Dougados et al., 2010; Yanaba et al., 2015) for TNF inhibitors, and MRI (Behrens et al., 2022) for IL‐17 inhibitors. While data exist for JAK inhibitors on MRI improvements in axial spine inflammation (Maksymowych et al., 2018, 2022; van der Heijde et al., 2018), there is a lack of data on peripheral enthesitis imaging, and it remains unknown whether improvements in the enthesitis scores (LEI/MASES/SPARCC) translates into improvements in MRI abnormalities such as bone marrow oedema; or ultrasound abnormalities, such as insertion doppler signal, erosion, calcifications/enthesophytes, entheseal thickness and hypoechogenicity (Balint et al., 2018).…”

Effect of Ixekizumab on Enthesitis-related arthritis non-responsive to anti-TNF treatment, a case report

“…IL-17A inhibitors were demonstrated to be effective in entheseal in ammation in adult's PsA and SpA. In a phase 3b clinical trial, greater improvements with secukinumab (a fully human monoclonal antibody that directly inhibits IL-17A) were observed in heel enthesitis and global assessment of disease activity [7] . At present, there are few data about the e cacy and safety of inhibition IL-17A for the treatment of pediatric enthesitis and ERA.…”

“…Interleukin (IL)-17A is a proin ammatory cytokine, involving in joint in ammation and joint erosion, mostly reported in the pathogenesis of psoriasis arthritis (PsA) and AS [5] . Activation of IL-17/IL-23 axis was positively correlated with HLA-B27 and was found to be involved in the pathogenesis of enthesitis [6,7] . Ixekizumab is a fully humanized immunoglobulin G4 that selectively neutralizes IL-17A, which has been guideline approved for the treatment of PsA and AS, after TNF inhibitors failure in adults [8] .…”

Efficacy and safety of biological DMARDs: a systematic literature review informing the 2022 update of the ASAS-EULAR recommendations for the management of axial spondyloarthritis

“…In total, 14 placebo-controlled trials assessed the efficacy of IL-17i (Table 2, Supplementary Tables S3.37-S3.66). [25][26][27][28][29][30][31][32][33][34][35][36][37][38] Patients with r-axSpA on secukinumab showed greater improvement compared to placebo in two phase III trials (ASAS20 58.1-60.5% versus 36.6-36.8%, low/unclear RoB). 25,27 Another phase III trial at low RoB saw numerically higher response rates for secukinumab compared to placebo in patients with r-axSpA, although results were not statistically significant (ASAS20 59.5-61.5% versus 47.0%) (Table 3).…”