Evaluation of the change in structural radiographic sacroiliac joint damage after 2 years of etanercept therapy (EMBARK trial) in comparison to a contemporary control cohort (DESIR cohort) in recent onset axial spondyloarthritis

Dougados, Maxime; Maksymowych, Walter P.; Landewé, Robert; Moltó, Anna; Claudepierre, Pascal; Hooge, M. de; Lambert, Robert G.; Bonin, R.; Bukowski, Jack F.; Jones, Heather; Logeart, I.; Pedersen, Ron; Szumski, Annette; Vlahos, Bonnie; Heijde, Desirée van der

doi:10.1136/annrheumdis-2017-212008

Cited by 42 publications

(38 citation statements)

References 37 publications

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“…Our data from the longitudinal analysis, consistent with the findings of previous studies , showed a positive and independent association between elevated CRP level, the presence of osteitis on MRI, and progression of radiographic sacroiliitis in patients with early axial SpA. The level of osteitis on MRI could be reduced in these patients after 3 years of continuous treatment with etanercept, as previously described .…”

Section: Discussionsupporting

confidence: 91%

“…In another analysis of the 2‐year progression rate from nonradiographic axial SpA to AS in patients treated with etanercept, the Study Comparing Etanercept Against a Placebo for Etanercept on a Background Nonsteroidal Antiinflammatory Drug in the Treatment of Early Spondyloarthritis Patients Who Do Not Have X‐ray Structural Changes (EMBARK), almost no progression was reported over 2 years . This might again be related to a lower proportion of patients with active inflammation or a lower extent of inflammation on MRI of the SI joints, a known risk factor for progression of radiographic sacroiliitis , in the EMBARK study as compared to the ESTHER population. The evidence of a deceleration of structural damage progression in the SI joint with increasing duration of anti‐TNF therapy shown here seems congruent with the retardation of the spine progression seen in AS patients treated long‐term with TNF inhibitors .…”

Section: Discussionmentioning

confidence: 99%

“…So far, only one study has shown some deceleration of radiographic sacroiliitis progression over 2 years of treatment with the tumor necrosis factor (TNF) inhibitor etanercept in patients with nonradiographic axial SpA as compared to a historical control group . No long‐term studies have addressed this question to date, although it has been shown that in the case of the spine the progression rate might decrease over time in patients receiving long‐term anti‐TNF therapy .…”

Section: Introductionmentioning

confidence: 99%

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Progression of Structural Damage in the Sacroiliac Joints in Patients With Early Axial Spondyloarthritis During Long‐Term Anti–Tumor Necrosis Factor Treatment: Six‐Year Results of Continuous Treatment With Etanercept

Rodriguez

Hermann

Weiß

et al. 2019

Arthritis & Rheumatology

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Objective. To evaluate radiographic progression in the sacroiliac (SI) joints and to identify its predictors during long-term treatment (up to 6 years) with the tumor necrosis factor (TNF) inhibitor etanercept in patients with early axial spondyloarthritis (SpA).Methods. Patients with early axial SpA who were treated with etanercept for up to 6 years in the Etanercept versus Sulfasalazine in Early Axial Spondyloarthritis (ESTHER) trial were selected based on the availability of radiographs of the SI joints. Two readers who were blinded with regard to clinical data scored the radiographs according to the modified New York criteria (range 0-4 per SI joint). A sacroiliitis sum score (total range 0-8) was calculated as the mean of the scores of the 2 readers. Active and chronic inflammatory changes in the SI joints on magnetic resonance imaging (MRI) performed at baseline, year 2, and year 4 were assessed according to the Berlin MRI scoring system.Results. Of the 76 patients originally included in the study, 42 had radiographs of the SI joints available at baseline and at least 1 follow-up time point (year 2, 4, or 6). The mean ± SD change in the sacroiliitis sum score was 0.13 ± 0.73, −0.27 ± 0.76, and −0.09 ± 0.68, in the time intervals baseline to year 2, year 2 to year 4, and year 4 to year 6, respectively. In the longitudinal mixed model analysis, elevated C-reactive protein level (β = 0.58 [95% confidence interval 0.24, 0.91]) and MRI SI joint osteitis score (β = 0.06 [95% confidence interval 0.03, 0.10]) were independently associated with progression of the sacroiliitis sum score.Conclusion. Our findings indicate that long-term anti-TNF therapy decelerates the progression of structural damage in the SI joints. Elevated CRP level and presence of osteitis on MRI were independently associated with radiographic sacroiliitis progression.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Progression of Structural Damage in the Sacroiliac Joints in Patients With Early Axial Spondyloarthritis During Long‐Term Anti–Tumor Necrosis Factor Treatment: Six‐Year Results of Continuous Treatment With Etanercept

Rodriguez

Hermann

Weiß

et al. 2019

Arthritis & Rheumatology

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“…Only 2 studies showed radiographic changes at the SI joint. Minhas et al reported an odds ratio of 0.06 (95% CI 0.004, 0.99) for the change in the BASRI SI joint score (measuring radiographic change in the SI joint) in the TNFi‐treated group compared to the biologics‐naive group in the PSOAS cohort .…”

Section: Resultsmentioning

confidence: 99%

Effect of Therapy on Radiographic Progression in Axial Spondyloarthritis: A Systematic Review and Meta‐Analysis

Karmacharya

Duarte‐García

Dubreuil

et al. 2020

Arthritis & Rheumatology

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Objective. To investigate the effect of therapies on radiographic progression in patients with axial spondyloarthritis (SpA). Methods. A comprehensive database search for studies assessing radiographic progression in axial SpA (particular treatment versus no treatment of interest) was performed. Study-specific standardized mean differences in treatment outcomes at 2 and ≥4 years were estimated and combined using random-effects models.Results. Twenty-four studies in patients with axial SpA were identified, of which 18 involved tumor necrosis factor inhibitors (TNFi), 8 involved nonsteroidal antiinflammatory drugs (NSAIDs), and 1 involved secukinumab. Spinal radiographic progression, as measured by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), was not significantly different between TNFi-treated and biologics-naive patients at 2 years (mSASSS difference −0.73 [95% confidence interval (95% CI) −1.52, 0.12], I 2 = 28%) and ≥4 years (mSASSS difference −2.03 [95% CI −4.63, 0.72], I 2 = 63%). Sensitivity analyses restricted to studies with a low risk of bias showed a significant difference in spinal radiographic progression between TNFi-treated and biologics-naive patients at ≥4 years (mSASSS difference −2.17 [95% CI −4.19, −0.15]). No significant difference in spinal radiographic progression was observed between NSAID-treated and control patients (mSASSS difference −0.30 [95% CI −2.62, 1.31], I 2 = 71%) or between secukinumab-treated and biologics-naive patients (mSASSS difference −0.34 [95% CI −0.85, 0.17]). With regard to treatment differences in patients with nonradiographic axial SpA or in patients with radiographic progression measured using the sacroiliac joint score, an insufficient number of studies were available for analysis.Conclusion. Although no significant protective effect of TNFi treatment on spinal radiographic progression was seen over the course of 2 years or ≥4 years in patients with axial SpA, our analysis restricted to studies with a low risk of bias showed a protective effect of TNFi after ≥4 years. Therefore, long-term TNFi exposure might confer beneficial effects on spinal radiographic progression in axial SpA. No difference in radiographic progression at 2 years was seen in either the NSAID or secukinumab treatment groups compared to their controls. Future studies should explore the effects of biologic treatment on radiographic progression, as well as the effects of long-term biologics exposure, in patients with early axial SpA or those with nonradiographic axial SpA.

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“…Такая высокая частота перехода нерентгенологического аксСпА в АС описана впервые. По результатам других когортных исследований она составляет 5-6% [9,16]. С чем связано такое большое расхождение, пока не ясно.…”

Section: Discussionunclassified

Disease activity and two-year sacroiliac joint changes according to instrumental study findings in a CoRSAr cohort of patients with early axial spondyloarthritis

Эрдес¹,

Румянцева²,

Смирнов³

et al. 2019

Naučno-praktičeskaâ revmatologiâ

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The evolution of axial spondyloarthritis (axSpA) and the transition of its nonradiographic to radiographic stage, when ankylosing spondylitis (AS) can be diagnosed, concern many researchers. To clarify this issue, an active search for predictors of the progression of this disease is underway; special cohort studies are being conducted.Objective: to analyze two-year changes in the magnetic resonance imaging (MRI) signs of sacroiliac joint (SIJ) inflammation and disease activity in patients with axSpA who form a Moscow CoRSAr cohort (a Cohort of early SpondylArthritis) and the role of these indicators in the progression of sacroiliitis.Subjects and methods. The investigation enrolled 68 CoRSAr cohort patients followed up for two years. All the patients underwent pelvic radiography and SIJ MRI at inclusion in the cohort and then every year. At inclusion in the cohort, nonradiographic axSpA was present in 28 patients, and AS was in 40. Disease activity was determined by BASDAI and ASDAS-CRP. The progression of sacroiliitis was assessed by the total scores of radiographic sacroiliitis.Results and discussion. The patients' age at inclusion in the cohort averaged 28.5±5.8 years, with a mean disease duration of 24.1±15.4 months and a male proportion of 51.5%; the HLA-B27-positive patients were 92.6%. At two years, 39% of the patients with nonradiographic axSpA went to the AS group. 24-month sacroiliitis progression was observed in 40% of the patients. Disease activity had little impact on the progression of sacroiliitis.Conclusion. Over two years, almost 40% of patients with axSpA showed an increase in the radiographic stage of sacroiliitis in the CoRSar cohort; this progression was primarily associated with the foci of osteitis according to MRI and correlated little with the activity of the disease.

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Evaluation of the change in structural radiographic sacroiliac joint damage after 2 years of etanercept therapy (EMBARK trial) in comparison to a contemporary control cohort (DESIR cohort) in recent onset axial spondyloarthritis

Cited by 42 publications

References 37 publications

Progression of Structural Damage in the Sacroiliac Joints in Patients With Early Axial Spondyloarthritis During Long‐Term Anti–Tumor Necrosis Factor Treatment: Six‐Year Results of Continuous Treatment With Etanercept

Progression of Structural Damage in the Sacroiliac Joints in Patients With Early Axial Spondyloarthritis During Long‐Term Anti–Tumor Necrosis Factor Treatment: Six‐Year Results of Continuous Treatment With Etanercept

Effect of Therapy on Radiographic Progression in Axial Spondyloarthritis: A Systematic Review and Meta‐Analysis

Disease activity and two-year sacroiliac joint changes according to instrumental study findings in a CoRSAr cohort of patients with early axial spondyloarthritis

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