Effects of Long‐Term Etanercept Treatment on Clinical Outcomes and Objective Signs of Inflammation in Early Nonradiographic Axial Spondyloarthritis: 104‐Week Results From a Randomized, Placebo‐Controlled Study

Dougados, Maxime; Heijde, Desirée van der; Sieper, Joachim; Braun, Jürgen; Citera, Gustavo; Lenaerts, Jan; Bosch, Filip Van den; Wei, James Cheng‐Chung; Pedersen, Ron; Bonin, R.; Jones, Heather; Marshall, L.; Logeart, I.; Vlahos, Bonnie; Bukowski, Jack F.; Maksymowych, Walter P.

doi:10.1002/acr.23276

Cited by 32 publications

(29 citation statements)

References 17 publications

(26 reference statements)

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“…In contrast to AS, there is still limited understanding of the disease course and appropriate long-term management of patients with nr-axSpA. The present work adds to the body of evidence that clinical and MRI improvements can be maintained with long-term anti-TNF therapy in patients with nr-axSpA classified by ASAS criteria [ 22 , 23 ]. Further, it provides important insights into the relationship between clinical and MRI remission in nr-axSpA, as well as the significance of sustained clinical remission for achieving normal physical function.…”

Section: Discussionmentioning

confidence: 96%

Clinical and MRI remission in patients with nonradiographic axial spondyloarthritis who received long-term open-label adalimumab treatment: 3-year results of the ABILITY-1 trial

et al. 2018

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BackgroundAdalimumab was effective in treating patients with nonradiographic axial spondyloarthritis (nr-axSpA) in the 12-week ABILITY-1 trial. We present long-term efficacy and safety results of adalimumab from the open-label ABILITY-1 extension, including the relationship between clinical and magnetic resonance imaging (MRI) remission and impact of sustained clinical remission on physical function.MethodsPatients received adalimumab 40 mg every other week or placebo for 12 weeks, then open-label adalimumab for up to 144 weeks. Clinical and safety data were collected through 3 years, and MRI data were collected until 2 years. Analyses were performed in the total population and subpopulation with positive MRI and/or elevated C-reactive protein (MRI/CRP-positive) at baseline. Clinical and MRI remission definitions included Ankylosing Spondylitis Disease Activity Score inactive disease (ASDAS ID; score < 1.3) and Spondyloarthritis Research Consortium of Canada (SPARCC) MRI score < 2 for sacroiliac joints (SIJs), spine, or both. Physical function was assessed using the Bath Ankylosing Spondylitis Functional Index.ResultsOverall, 185 patients were included in the total population and 142 in the MRI/CRP-positive subpopulation; 65% and 68%, respectively, completed 3 years. Clinical, functional, and MRI improvements were similar and equally sustainable in both populations. At year 3, the percentages of patients in ASDAS ID in the MRI/CRP-positive subpopulation were 30%/33% (nonresponder imputation) and 46%/49% (observed) for those initially receiving adalimumab/placebo. At years 1 and 2, patients in ASDAS ID vs not had significantly greater improvements in SPARCC SIJ scores from baseline (P < 0.001). Among patients with baseline MRI scores ≥ 2 who achieved ASDAS ID at year 2, 44–68% also had MRI remission. Significantly more patients with sustained ASDAS ID through year 2 or 3 vs without achieved normal physical function (100% vs 48%; 100% vs 44%; both P < 0.001). No new safety concerns were observed.ConclusionsIn the ABILITY-1 study of nr-axSpA, adalimumab therapy provided sustained clinical and functional improvements through 3 years, as well as suppression of MRI axial inflammation, which was greater in patients who achieved clinical remission. Sustained clinical remission was associated with increased attainment of normal physical function. The safety profile of adalimumab was consistent with prior studies.Trial registrationClinicalTrials.gov, NCT00939003; registered on July 10, 2009.Electronic supplementary materialThe online version of this article (10.1186/s13075-018-1556-5) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 96%

Clinical and MRI remission in patients with nonradiographic axial spondyloarthritis who received long-term open-label adalimumab treatment: 3-year results of the ABILITY-1 trial

et al. 2018

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“…EMBARK (Effect of Etanercept on Symptoms and Objective Inflammation in nr-axSpA, a 104 week study; ClinicalTrials.gov identifier: NCT01258738) 9 was a randomised, controlled, phase 3b, 104 week clinical trial to evaluate the safety and efficacy of etanercept in patients with nr-axSpA. 10 11 Patients had axSpA per Assessment of SpondyloArthritis international Society (ASAS) criteria 12 13 without meeting the mNY criteria for radiographic axSpA.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2017

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ObjectiveTo 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).MethodsPatients 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.ResultsMRI 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.ConclusionTreatment 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 numberNCT01258738; Post-results.

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“…Patient disposition at Week 104 has been described previously [7]. Briefly, of the 215 randomized patients, 169 completed 104 weeks of treatment.…”

Section: Resultsmentioning

confidence: 99%

“…Briefly, of the 215 randomized patients, 169 completed 104 weeks of treatment. At Baseline, the mean age was 32 years, 40% of patients were women, and the mean duration of disease symptoms was 2.4 years [7].…”

Section: Resultsmentioning

confidence: 99%

“…Results from the EMBARK study have demonstrated that patients with early, active, non-steroidal antiinflammatory drug (NSAID)-resistant nr-axSpA can be treated effectively with the tumor necrosis factor inhibitor etanercept [6], and that the early improvement in clinical outcomes and markers of inflammation is maintained over 104 weeks [7,8]. Some short-term improvements in PRO measures (up to 24 weeks) have also been noted [9].…”

Section: Introductionmentioning

confidence: 99%

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Relationship between disease activity status or clinical response and patient-reported outcomes in patients with non-radiographic axial spondyloarthritis: 104-week results from the randomized controlled EMBARK study

Dougados

Heijde

Tsai

et al. 2020

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Background: We assessed the external validity of composite indices Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Assessment in SpondyloArthritis international Society (ASAS) 40 response (ASAS40) by evaluating the correlations between the changes in some patient reported outcomes (PROs) for patients with non-radiographic axial spondyloarthritis (nr-axSpA) and the changes in the scores of the composite indices. Methods: This was a post-hoc analysis of data from the EMBARK study in patients with nr-axSpA treated with etanercept. PROs were grouped according to ASDAS status (inactive [< 1.3], low [≥ 1.3 to < 2.1], high [≥ 2.1 to ≤3.5], and very high [> 3.5]), patient achievement of > 50% improvement in BASDAI (BASDAI50 responders), and > 40% improvement in ASAS (ASAS40 responders) at 104 weeks. Analyses were conducted on observed cases available at Week 104. Changes in PROs from Baseline to Week 104 were assessed using analysis of covariance with adjustment for baseline with linear contrast. Results: Higher ASDAS disease activity at 104 weeks was associated with lower long-term improvement from baseline in PROs (e.g., total back pain [visual analog scale, cm (95% confidence interval):

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Effects of Long‐Term Etanercept Treatment on Clinical Outcomes and Objective Signs of Inflammation in Early Nonradiographic Axial Spondyloarthritis: 104‐Week Results From a Randomized, Placebo‐Controlled Study

Abstract: Patients with early, active nonradiographic axial SpA and an inadequate response to at least 2 NSAIDs demonstrated improvement in clinical and imaging outcomes that were sustained through 104 weeks of etanercept treatment.

Cited by 32 publications

References 17 publications

Clinical and MRI remission in patients with nonradiographic axial spondyloarthritis who received long-term open-label adalimumab treatment: 3-year results of the ABILITY-1 trial

Clinical and MRI remission in patients with nonradiographic axial spondyloarthritis who received long-term open-label adalimumab treatment: 3-year results of the ABILITY-1 trial

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

Relationship between disease activity status or clinical response and patient-reported outcomes in patients with non-radiographic axial spondyloarthritis: 104-week results from the randomized controlled EMBARK study

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