Resolution of synovitis and arrest of catabolic and anabolic bone changes in patients with psoriatic arthritis by IL-17A blockade with secukinumab: results from the prospective PSARTROS study

Abstract

Background: Although the effects of interleukin-17A (IL-17A) inhibition on the signs and symptoms of psoriatic arthritis (PsA) are well defined, little is known about its impact of local inflammatory and structural changes in the joints. The PSARTROS study was designed to elucidate the effects of IL-17A inhibition on inflammation and bone changes in joints affected by PsA.

Methods: This was a prospective open-label study in 20 patients with active PsA receiving 24 weeks of treatment with the IL-17A inhibitor secukinumab. Magnetic resonance imaging (MRI), power Doppler ultrasound (PDUS), and high-resolution peripheral quantitative computer tomography (HR-pQCT) of the hands were performed at baseline and after 24 weeks to assess synovitis, periarticular inflammation, bone erosion, enthesiophyte formation, and bone structure. Demographic and clinical measures of joint disease (DAPSA and DAS28-ESR), skin disease (PASI and BSA), and composite measures (minimal disease activity, or MDA) were also recorded.

Results: Treatment with secukinumab led to significant improvement of signs and symptoms of PsA; 46% reached MDA and 52% DAPSA low disease activity. MRI synovitis (P = 0.034) and signal in PDUS (P = 0.030) significantly decreased after 24 weeks of treatment. Bone erosions in MRI and HR-pQCT and enthesiophytes in the HR-pQCT did not show any progression, and structural integrity and functional bone strength remained stable.

Conclusions: IL-17 inhibition by secukinumab over 24 weeks led to a significant decrease of synovial inflammation and no progression of catabolic and anabolic bone changes in the joints of patients with PsA.

Trial registration: ClinicalTrials.gov Identifier: NCT02483234 , June 26, 2015; retrospectively registered.

Keywords: Bone; Enthesiophytes; Erosions; Psoriatic arthritis; Synovitis; bDMARDs.

Fig. 1

Prevalence of inflammatory and structural changes in the joints of patients with psoriatic arthritis. a On left, baseline imaging analysis and comparative presentation of the prevalence of synovitis, bone erosions, and enthesiophytes in power Doppler ultrasound (PDUS), magnetic resonance imaging (MRI), and high-resolution peripheral quantitative computed tomography (HR-pQCT); on right, prevalence of enthesiophytes according to size using HR-pQCT (grade 1: height < 4 mm, grade 2: height ≥ 4 mm, grade 3: diffuse proliferation). b Coronal and axial images of the same enthesiophytes (upper panel: grade 1, lower panel: grade 3) in MRI and HR-pQCT. Arrow indicates the lesion. Abbreviation: N/A not applicable

Fig. 2

Effects of secukinumab treatment on the inflammatory changes in the joints of patients with psoriatic arthritis. a Comparison of inflammatory changes in the joints of psoriatic arthritis (PsA) patients using magnetic resonance imaging (MRI) at baseline (BL) and after 24 weeks (Wk24) of secukinumab treatment. Psoriatic arthritis MRI scores (PsAMRIS) for synovitis and total PsAMRIS scores are shown. b Representative coronal T1-weighted fat-suppressed post-gadolinium MRI images of the hand of the same patient with PsA at baseline and after 24 weeks are depicted. Baseline image shows synovitis (arrows) and periarticular inflammation at enthesial sites (arrowheads), which resolved after 24 weeks of secukinumab treatment. c Comparison of inflammatory changes in the joints of PsA patients using power Doppler ultrasound (PDUS) at baseline (BL) and after 24 weeks (Wk24) of secukinumab treatment. OMERACT ultrasound scores for synovial hypertrophy and power Doppler activity as well as global OMERACT ultrasound scores are shown. Data are presented as median and interquartile ranges. *P ≤0.05; **P ≤0.01

Fig. 3

Effects of secukinumab treatment on the articular and extra-articular structural bone changes in patients with psoriatic arthritis. a Comparison of bone erosions in the joints of psoriatic arthritis (PsA) patients using magnetic resonance imaging (MRI, left) and high-resolution peripheral quantitative computed tomography (HR-pQCT, right) at baseline (BL) and after 24 weeks (Wk24) of secukinumab treatment. MRI data represent Psoriatic arthritis MRI scores (PsAMRIS) for erosions, and HR-pQCT data represent erosion volumes. b Comparison of enthesiophytes in the joints of PsA patients using MRI (left) and HR-pQCT (right) at baseline (BL) and after 24 weeks (Wk24) of secukinumab treatment. MRI data represent Psoriatic arthritis MRI scores (PsAMRIS) for proliferations, and HR-pQCT data represent enthesiophyte grades according to size. c Comparison of bone micro-structural data of the distal radius of PsA patients using HR-pQCT at baseline (BL) and after 24 weeks (Wk24) of secukinumab treatment. Cortical and trabecular volumetric bone density (vBMD), cortical thickness, and trabecular numbers are shown. d Comparison of biomechanical properties of radial bones of PsA patients using HR-pQCT measurements at baseline (BL) and after 24 weeks (Wk24) of secukinumab treatment. Data show failure load and bone stiffness based on micro-finite element analysis. Data are presented as median and interquartile ranges. Abbreviations: kN kiloNewton, mgHA/cm³ milligram of hydroxyapatite per cube centimeter, N Newton