Dataset Information

The Effect of Etanercept in Nonradiographic Axial Spondyloarthritis by Stratified C-Reactive Protein Levels.

ABSTRACT:

Objective

Biological agents have shown markedly different response rates by baseline C-reactive protein (CRP). Here, we determine the response of patients with nonradiographic axial spondyloarthritis (nr-axSpA) to etanercept stratified by their baseline CRP level.

Methods

The EMBARK trial was a phase 3, randomized, double-blind, placebo-controlled study of etanercept in nr-axSpA. The primary endpoint was Assessment of Spondyloarthritis International Society (ASAS) 40 at Week 12, the conclusion of the double-blind phase. It recruited patients who met the ASAS criteria for axial spondyloarthritis, and sacroiliac joint magnetic resonance scans were completed on all patients. In this post hoc analysis, we analyzed outcomes by baseline C-reactive protein (CRP) level of less than 5 mg/L, 5 mg/L to 10 mg/L, and greater than 10 mg/L. The clinical trial outcome data were accessed via the Vivli platform.

Results

In the less than 5 mg/L CRP group treated with etanercept, the ASAS20 response, ASAS40 response, Ankylosing Spondylitis Disease Activity Score-CRP (ASDAS-CRP), and ASDAS-ESR (erythrocyte sedimentation rate) outcomes were 49% (P = 0.84), 26% (P = 0.14), 42% (P = 0.002), and 44% (P = 0.006), respectively. In the 5 to 10 mg/L CRP group treated with etanercept, the ASAS20 response, ASAS40 response, ASDAS-CRP, and ASDAS-ESR outcomes were 56% (P = 0.99), 31% (P = 0.40), 56% (P = 0.16), and 50% (P = 0.11), respectively. In the greater than10 mg/L CRP group treated with etanercept, the ASAS20 response, ASAS40 response, ASDAS-CRP, and ASDAS-ESR outcomes were 74% (P = 0.02), 68% (P = 0.003), 82% (P = 0.005), and 50% (P = 0.001), respectively.

Conclusion

Although there are reduced ASAS20 and ASAS40 response rates in the groups with baseline CRP less than 10 mg/L, there remain clinically relevant responses when the composite outcome measures ASDAS-CRP or ASDAS-ESR were used, and this should be considered when deciding on thresholds for reimbursement.

SUBMITTER: Tam HKJ

PROVIDER: S-EPMC8516106 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Publications

The Effect of Etanercept in Nonradiographic Axial Spondyloarthritis by Stratified C-Reactive Protein Levels.

Tam Hoi Ki Joshua HKJ Nash Peter P Robinson Philip C PC

ACR open rheumatology 20210818 10

<h4>Objective</h4>Biological agents have shown markedly different response rates by baseline C-reactive protein (CRP). Here, we determine the response of patients with nonradiographic axial spondyloarthritis (nr-axSpA) to etanercept stratified by their baseline CRP level.<h4>Methods</h4>The EMBARK trial was a phase 3, randomized, double-blind, placebo-controlled study of etanercept in nr-axSpA. The primary endpoint was Assessment of Spondyloarthritis International Society (ASAS) 40 at Week 12, t ...[more]

PMID: 34405589

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Project description:The Assessment of Spondyloarthritis International Society (ASAS) health index (HI) is a novel tool for approaching disability, health, and functioning in spondyloarthritis (SpA). In the present study we compared ASAS HI between patients with ankylosing spondylitis (AS) and those with nonradiographic axial SpA (nr-axSpA). In addition, we identified predictors of ASAS HI. We designed this cross-sectional study using data from the Catholic Axial Spondyloarthritis COhort (CASCO), a prospective cohort from a single tertiary hospital. We compared baseline characteristics, including ASAS HI, between AS and nr-axSpA, and determined the frequency of each item constituting the ASAS HI. We used linear regression analysis to identify factors associated with ASAS HI. Total of 357 patients with axSpA-261 with AS and 96 with nr-axSpA-were included in analysis. AS patients were older and had higher ASAS HI than nr-axSpA. Among ASAS HI items, pain (item No. 1) and energy/drive (item No. 5) were the most common areas for which axSpA patients experienced discomfort. ASAS HI correlated with other SpA-related parameters such as BASDAI, ASDAS, and BASFI. Multivariable regression analysis of the axSpA group showed that high NSAID intake and mSASSS were positively associated with ASAS HI, whereas higher economic status and alcohol consumption were negatively associated with ASAS HI. Results were consistent in the AS group on subgroup analysis, whereas alcohol consumption was the only factor significantly associated with ASAS HI in the nr-axSpA group. In the present cohort study, patients with AS had poorer health status (higher ASAS HI) than those with nr-axSpA. Items proposed by AS patients (items No. 1 and 5) were the most frequently checked areas as axSpA patients feel discomfort, and this support that ASAS HI could practically assess actual discomfort of axSpA patient. ASAS HI was well correlated with known disease parameters, including activity, function, and quality of life; therefore, ASAS HI could be used in the future to represent the health status of SpA in a systematic way. Spinal structural damage (higher mSASSS), high NSAID intake, alcohol consumption, and economic status were predictors of ASAS HI in patients with axSpA, especially those with AS.

Project description:ObjectiveThe natural history of nonradiographic axial spondyloarthritis (SpA) is incompletely characterized, and there are concerns that nonsteroidal antiinflammatory drugs provide inadequate disease control in patients with active disease. This study was undertaken to investigate the effects of certolizumab pegol (CZP), an anti-tumor necrosis factor treatment, in patients with nonradiographic axial SpA with objective signs of inflammation.MethodsIn this ongoing parallel-group double-blind study, adults with active disease were recruited from 80 centers in Australia, Europe, North America, and Taiwan, and were randomized 1:1 to receive placebo or CZP (400 mg at weeks 0, 2, and 4, followed by 200 mg every 2 weeks) in addition to nonbiologic background medication (NBBM). Switching to open-label CZP (or other biologic) or making background medication changes was permitted at any point during the trial, although changes before week 12 were discouraged. The primary end point was the proportion of patients achieving major improvement (MI) (i.e., a ≥2.0-point decrease in the score from baseline or achievement of the lowest possible score [0.6]) in the Ankylosing Spondylitis Disease Activity Score (ASDAS) at week 52.ResultsA total of 317 patients were randomized to receive placebo plus NBBM (n = 158) or CZP plus NBBM (n = 159). ASDAS-MI at week 52 was achieved in 47.2% (75 of 159) of CZP plus NBBM patients, which was significantly greater (P < 0.0001) than the 7.0% (11 of 158) of placebo plus NBBM patients in whom ASDAS-MI was achieved. Of the placebo plus NBBM patients, 60.8% (96 of 158) switched to open-label treatment before week 52 compared to 12.6% (20 of 159) of the CZP plus NBBM patients.ConclusionAdding CZP to background medication is superior to adding placebo in patients with active nonradiographic axial SpA. These results indicate that remission in nonradiographic axial SpA treated without biologics occurs infrequently, demonstrating the need for treatment beyond nonbiologic therapy.

Project description:ObjectiveTo investigate the efficacy of 16-week treatment with etanercept (ETN) in patients with suspected nonradiographic axial spondyloarthritis (SpA).MethodsTumor necrosis factor inhibitor-naive patients with inflammatory back pain with at least 2 SpA features and high disease activity (Bath Ankylosing Spondylitis Disease Activity Index score ≥4), without the requirement of a positive finding on magnetic resonance imaging (MRI) of the sacroiliac (SI) joint and/or elevated C-reactive protein (CRP) level, were randomized (1:1) to receive ETN (n = 40) or placebo (n = 40) for 16 weeks and subsequently were followed up for a further 8 weeks (to 24 weeks from baseline) without study medication. The primary end point was the Assessment of SpondyloArthritis international Society 20 (ASAS20) response at 16 weeks. Secondary end points included the Ankylosing Spondylitis Disease Activity Score (ASDAS) and changes in disease parameters, including the Bath Ankylosing Spondylitis Metrology Index (BASMI), CRP level, erythrocyte sedimentation rate (ESR), and Spondyloarthritis Research Consortium of Canada index scores (MRI of the SI joint), after 16 and 24 weeks.ResultsPatient characteristics at baseline were comparable between the ETN and placebo groups. At 16 weeks, there was no significant difference in the percentage of patients exhibiting ASAS20 response between the ETN group (6 patients [16.7%]) and the placebo group (4 patients [11.1%]) (relative risk 0.7 [95% confidence interval 0.2-2.2], P = 0.5). Only the ESR showed more improvement in the ETN group compared to the placebo group at 16 weeks (decreases of 2.2 mm/hour and 1.4 mm/hour, respectively), but the difference did not reach statistical significance. Between 16 and 24 weeks, without study medication, the BASMI, CRP level, and ESR had worsened to a greater extent in the ETN group compared to the placebo group, with the difference being significant for the CRP level.ConclusionThis study shows that in patients with suspected nonradiographic axial SpA with high disease activity but without the requirement of a positive finding on SI joint MRI and/or elevated CRP level, treatment with ETN is not effective.

Project description:ObjectiveTumor necrosis factor inhibitors (TNFi) are an effective treatment for non-radiographic axial spondyloarthritis (nr-axSpA). To be eligible, however, many authorities require patients with nr-axSpA to show active sacroiliitis on magnetic resonance imaging (MRI) and/or an elevated C-reactive protein (CRP) level, possibly resulting in a perception that patients with nr-axSpA without both factors have only low responses to TNFi treatment. We evaluated clinical responses to certolizumab pegol (CZP) in patients with nr-axSpA stratified by baseline MRI/CRP status.MethodsC-axSpAnd was a phase 3, multicenter study on CZP in adult patients with active nr-axSpA and objective signs of inflammation. This analysis assessed efficacy of CZP over the 52-week randomized, double-blind, placebo-controlled period in patients stratified into subgroups based on the presence of active sacroiliitis on MRI and CRP level at baseline.ResultsCZP-treated patients across all MRI/CRP subgroups achieved clinical responses greater than placebo. Across outcome measures, CZP-treated MRI+/CRP+ patients demonstrated the greatest clinical responses, but substantial improvements were also observed in CZP-treated MRI+/CRP- and MRI-/CRP+ patients. Ankylosing Spondylitis Disease Activity Score Major Improvement response rates at week 52 among CZP-treated patients (75.6% MRI+/CRP+; 47.5% MRI-/CRP+; and 29.7% MRI+/CRP-) were higher than rates in placebo groups (range: 3.9%-12.5%). Assessment of SpondyloArthritis international Society 40% response, Bath Ankylosing Spondylitis Disease Activity Index, and Bath Ankylosing Spondyloarthritis Functional Index had similar response patterns, although differences between the CZP-treated MRI/CRP subgroups were smaller. Clinical responses among CZP-treated patients were also observed in additional subgroups, including those with low Spondyloarthritis Research Consortium of Canada MRI sacroiliac joint inflammation scores and those with normal baseline CRP levels.ConclusionOur findings indicate that CZP treatment benefits patients with nr-axSpA across MRI+/CRP+, MRI-/CRP+, and MRI+/CRP- subgroups.

Project description:ObjectiveAxial spondyloarthritis (SpA) is a chronic inflammatory disease characterized by back pain and stiffness. The objective of this study was to determine whether golimumab is superior to placebo in patients with nonradiographic axial SpA.MethodsThis phase III, double-blind, randomized, placebo-controlled trial was performed to evaluate subcutaneous golimumab (50 mg) versus placebo in patients ages ≥18 years to ≤45 years who had active nonradiographic axial SpA according to the Assessment of SpondyloArthritis international Society (ASAS) criteria for ≤5 years since diagnosis, high disease activity, and an inadequate response to or intolerance of nonsteroidal antiinflammatory drugs. Patients were randomized 1:1 to receive golimumab or placebo subcutaneously every 4 weeks. The primary end point was 20% improvement according to the ASAS criteria (ASAS20) at week 16. Key secondary end points were an ASAS40 response, ASAS partial remission, 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and change in the Spondyloarthritis Research Consortium of Canada (SPARCC) magnetic resonance imaging (MRI) index for sacroiliac (SI) joint inflammation (SPARCC score).ResultsOf the 198 patients randomized, 197 were treated (97 received golimumab, and 100 received placebo). The mean age of the patients was 31 years, and 57.1% were male. At baseline, the mean ± SD BASDAI was 6.5 ± 1.5, the mean ± SD ASDAS was 3.5 ± 0.9, and the mean ± SD SPARCC score was 11.3 ± 14.0. The primary end point, an ASAS20 response, was achieved by significantly more patients in the golimumab group compared with the placebo group (71.1% versus 40.0%; P < 0.0001). An ASAS40 response was also achieved by significantly more patients in the golimumab group compared with the placebo group (56.7% versus 23.0%; P < 0.0001). The incidence of adverse events did not differ meaningfully between groups.ConclusionPatients with active nonradiographic axial SpA treated with golimumab had significantly greater improvement in symptoms compared with patients treated with placebo. Golimumab was well tolerated and had a favorable risk/benefit profile.

Dataset Information

The Effect of Etanercept in Nonradiographic Axial Spondyloarthritis by Stratified C-Reactive Protein Levels.

Objective

Methods

Results

Conclusion

Publications

The Effect of Etanercept in Nonradiographic Axial Spondyloarthritis by Stratified C-Reactive Protein Levels.

Similar Datasets

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