Structural changes in the sacroiliac joint on MRI and relationship to ASDAS inactive disease in axial spondyloarthritis: a 2-year study comparing treatment with etanercept in EMBARK to a contemporary control cohort in DESIR

Walter P Maksymowych, Pascal Claudepierre, Manouk de Hooge, Robert G Lambert, Robert Landewé, Anna Molto, Désirée van der Heijde, Jack F Bukowski, Heather Jones, Ron Pedersen, Annette Szumski, Bonnie Vlahos, Maxime Dougados, Walter P Maksymowych, Pascal Claudepierre, Manouk de Hooge, Robert G Lambert, Robert Landewé, Anna Molto, Désirée van der Heijde, Jack F Bukowski, Heather Jones, Ron Pedersen, Annette Szumski, Bonnie Vlahos, Maxime Dougados

Abstract

Background: Limited information is available on the impact of treatment with a tumor necrosis factor inhibitor (TNFi) on structural lesions in patients with recent-onset axial spondyloarthritis (axSpA). We compared 2-year structural lesion changes on magnetic resonance imaging (MRI) in the sacroiliac joints (SIJ) of patients with recent-onset axSpA receiving etanercept in a clinical trial (EMBARK) to similar patients not receiving biologics in a cohort study (DESIR). We also evaluated the relationship between the Ankylosing Spondylitis Disease Activity Score (ASDAS) and change in MRI structural parameters.

Methods: The difference between etanercept (EMBARK) and control (DESIR) in the net percentage of patients with structural lesion change was determined using the SpondyloArthritis Research Consortium of Canada SIJ Structural Score, with and without adjustment for baseline covariates. The relationship between sustained ASDAS inactive disease, defined as the presence of ASDAS < 1.3 for at least 2 consecutive time points 6 months apart, and structural lesion change was evaluated.

Results: This study included 163 patients from the EMBARK trial and 76 from DESIR. The net percentage of patients with erosion decrease was significantly greater for etanercept vs control: unadjusted: 23.9% vs 5.3%; P = 0.01, adjusted: 23.1% vs 2.9%; P = 0.01. For the patients attaining sustained ASDAS inactive disease on etanercept, erosion decrease was evident in significantly more than erosion increase: 34/104 (32.7%) vs 5/104 (4.8%); P < 0.001. A higher proportion had erosion decrease and backfill increase than patients in other ASDAS status categories. However, the trend across ASDAS categories was not significant and decrease in erosion was observed even in patients without a sustained ASDAS response.

Conclusions: These data show that a greater proportion of patients achieved regression of erosion with versus without etanercept. However, the link between achieving sustained ASDAS inactive disease and structural lesion change on MRI could not be clearly established.

Trial registration: EMBARK: ClinicalTrials.gov identifier: NCT01258738 , Registered 13 December 2010; DESIR: ClinicalTrials.gov identifier: NCT01648907 , Registered 24 July 2012.

Keywords: ASDAS; Anti-TNF; Axial spondyloarthritis; Etanercept; MRI; Sacroiliac joint.

Conflict of interest statement

WPM has received grant/research support from AbbVie, Novartis, and Pfizer, consulted for AbbVie, Boehringer, Celgene, Galapagos, Janssen, Lilly, Merck, Novartis, Pfizer, and UCB, and is the chief medical officer of CaRE Arthritis Ltd. PC has consulted for AbbVie, BMS, Celgene, Janssen, Novartis, Merck, Pfizer, Roche, UCB, and Lilly. MdH is an employee of MdH Research. RGL has consulted for AbbVie, Bioclinica, Janssen, Parexel, and UCB. RL has received grant/research support from AbbVie, Amgen, Centocor, Novartis, Pfizer, Roche, and UCB; consulted for AbbVie, Ablynx, Amgen, AstraZeneca, BMS, Celgene, Janssen, Galapagos, GlaxoSmithKline, Novartis, Novo-Nordisk, Merck, Pfizer, Roche, Schering-Plough, TiGenix, and UCB; and is Director of Rheumatology Consultancy BV. AM has received grant/research support from AbbVie, Pfizer, and UCB and consulted for AbbVie, Janssen, Merck, Novartis, Pfizer, Sanofi, and UCB. DvdH has consulted for AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, and UCB, and is the Director of Imaging Rheumatology bv. JFB, HJ, and RP were employees of Pfizer at the time the manuscript was written. BV is an employee of and owns stock in Pfizer. AS is an employee of Syneos Health and was contracted by Pfizer to provide statistical support for the development of this paper. MD has received grant/research support from Pfizer, AbbVie, UCB, Merck, and Lilly and has consulted for Pfizer, AbbVie, UCB, Merck, and Lilly.

No nonfinancial conflict of interest exists for any author.

Figures

Fig. 1
Fig. 1
Net percentage of patients with axial spondyloarthritis with decrease in erosion, unadjusted (a) and adjusted analysis (b); increase in backfill, unadjusted (c) and adjusted analysis (d), increase in fat metaplasia, unadjusted (e) and adjusted analysis (f), increase in ankylosis, unadjusted (g) and adjusted analysis (h), baseline to week 104
Fig. 2
Fig. 2
Cumulative probability of change in MRI structural lesion score in patients with axial spondyloarthritis for erosion (a) and backfill (b) over 104 weeks, average of the readers. MRI magnetic resonance imaging
Fig. 3
Fig. 3
Proportion of patients with axial spondyloarthritis with decrease or increase in erosion (a), increase or decrease in backfill (b) according to ASDAS outcome, baseline to week 104. ASDAS Ankylosing Spondylitis Disease Activity Score
Fig. 4
Fig. 4
Net percentage of patients with axial spondyloarthritis with decrease in erosion, unadjusted (a) and adjusted (b), and increase in backfill, unadjusted (c) and adjusted (d) according to ASDAS outcome, baseline to week 104. ASDAS Ankylosing Spondylitis Disease Activity Score

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