Modification of structural lesions on MRI of the sacroiliac joints by etanercept in the EMBARK trial: a 12-week randomised placebo-controlled trial in patients with non-radiographic axial spondyloarthritis

Abstract

Objective: To evaluate the impact on structural lesions observed on MRI in the sacroiliac joints (SIJ) at 12 weeks in patients with non-radiographic axial spondyloarthritis (nr-axSpA) receiving etanercept or placebo in EMBARK (Effect of Etanercept on Symptoms and Objective Inflammation in nr-axSpA, a 104 week study).

Methods: Patients were randomised to double-blind etanercept 50 mg/week or placebo for 12 weeks. Structural lesions at baseline and 12 weeks were scored by two independent readers using the Spondyloarthritis Research Consortium of Canada (SPARCC) SIJ structural score (SSS) on T1-weighted MRI. Change in SPARCC SSS and correlation with improvement in clinical outcomes was evaluated.

Results: MRI scans from 185 patients (etanercept, n=88; placebo, n=97) were reviewed. At baseline, there were no significant differences in mean SPARCC SSS between etanercept and placebo. From baseline to 12 weeks, change in mean SPARCC SSS was significantly greater for etanercept than placebo for erosion (-0.57 vs -0.08, respectively, adjusted p value=0.017) and backfill (0.36 vs 0.06, adjusted p value=0.022). A treatment difference was also present for the subgroup of patients with SIJ inflammation on MRI (SPARCC bone marrow oedema ≥2): erosion: -0.81 versus -0.13 for etanercept versus placebo, respectively, p=0.007; backfill: 0.48 versus 0.08, respectively, p=0.032. Decrease in erosion and increase in backfill correlated with improvement in more clinical outcomes for etanercept than placebo.

Conclusion: Treatment with etanercept was associated with significantly greater reduction in erosions and increase in backfill at 12 weeks compared with placebo, consistent with a very early reparative response to antitumour necrosis factor therapy. The impact on disease progression in spondyloarthritis should be studied further.

Trial registration number: NCT01258738; Post-results.

Keywords: anti-TNF; magnetic resonance imaging; spondyloarthritis.

Conflict of interest statement

Competing interests: WPM has received consulting fees from AbbVie, Amgen, Lilly, Janssen, Pfizer, Sanofi and UCB and is the chief medical officer of CaRE Arthritis Ltd. MD is a consultant for and has received research funding/grants from AbbVie, Lilly, Merck, Pfizer, Sanofi and UCB. HJ, RP, LM and JFB are employees of and own stock in Pfizer. AS is an employee of inVentiv Health and was contracted by Pfizer to provide statistical support for the development of this paper. SW and RGL have no competing interests to declare.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1

Mean change from baseline to week 12 with SE in (A) erosion, (B) erosion according to SPARCC BME ≥2 or

Figure 2

Cumulative probability of change from baseline to week 12 in (A) erosion, (B) backfill and (C) fat metaplasia, average of the readers. Erosion and fat metaplasia range in score from 0 to 40. Backfill ranges in score from 0 to 20.

Figure 3

Example images of erosion at baseline and backfill at 12 weeks on T1 weighted MRI in two patients. On the baseline scan, erosion is indicated by loss of the dark signal of iliac cortical bone and loss of the normal bright appearance of adjacent bone marrow. On the 12-week scan, backfill is evident as characterised by increased signal at the site of erosion clearly demarcated from adjacent normal marrow by dark signal with irregular contour reflecting sclerosis at the border of the eroded bone.