Sarilumab and adalimumab differential effects on bone remodelling and cardiovascular risk biomarkers, and predictions of treatment outcomes
Abstract Background Interleukin-6 (IL-6) is a pleiotropic cytokine that plays a key role in the pathogenesis of rheumatoid arthritis. Sarilumab is a human monoclonal antibody that binds membrane-bound and soluble IL-6 receptor-α to inhibit IL-6 signalling. The aim of this study was to compare the ef...
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doaj-9f7d47705237485b86eba702a5fcce612020-11-25T02:58:39ZengBMCArthritis Research & Therapy1478-63622020-04-0122111110.1186/s13075-020-02163-6Sarilumab and adalimumab differential effects on bone remodelling and cardiovascular risk biomarkers, and predictions of treatment outcomesCem Gabay0Gerd R. Burmester1Vibeke Strand2Jérôme Msihid3Moshe Zilberstein4Toshio Kimura5Hubert van Hoogstraten6Susan H. Boklage7Jonathan Sadeh8Neil M. H. Graham9Anita Boyapati10University Hospitals of GenevaCharité - University Medicine BerlinStanford UniversitySanofiSanofi GenzymeRegeneron Pharmaceuticals Inc.Sanofi GenzymeRegeneron Pharmaceuticals Inc.Sanofi GenzymeRegeneron Pharmaceuticals Inc.Regeneron Pharmaceuticals Inc.Abstract Background Interleukin-6 (IL-6) is a pleiotropic cytokine that plays a key role in the pathogenesis of rheumatoid arthritis. Sarilumab is a human monoclonal antibody that binds membrane-bound and soluble IL-6 receptor-α to inhibit IL-6 signalling. The aim of this study was to compare the effects of sarilumab and adalimumab (a tumour necrosis factor alpha inhibitor) monotherapy on levels of circulating biomarkers associated with the acute-phase response, bone remodelling, atherothrombosis, anaemia of chronic disease and markers purported to reflect synovial lymphoid and myeloid cell infiltrates, as well as the potential of these biomarkers to differentially predict clinical and patient-reported outcomes with sarilumab vs. adalimumab. Methods In this post hoc analysis, serum samples were analysed at baseline and prespecified post-treatment timepoints up to week 24 in adults with moderate-to-severe active rheumatoid arthritis intolerant of or inadequate responders to methotrexate from the MONARCH trial (NCT02332590). Results Greater reductions in C-reactive protein (CRP; − 94.0% vs. –24.0%), serum amyloid A (SAA; − 83.2% vs. –17.4%), total receptor activator of nuclear factor-κB ligand (RANKL; − 18.3% vs. 10.5%) and lipoprotein (a) (− 41.0% vs. –2.8%) were observed at week 24 with sarilumab vs. adalimumab, respectively (adjusted p < 0.0001). Greater increases in procollagen type 1 N-terminal propeptide (P1NP) were observed with sarilumab vs. adalimumab at week 24 (22.8% vs. 6.2%, p = 0.027). Patients with high baseline SAA, CRP and matrix metalloproteinase-3 (MMP-3) were more likely to achieve clinical efficacy, including American College of Rheumatology 20% improvement criteria and Disease Activity Score (28 joints)-CRP < 3.2, and report improvements in patient-reported outcomes, including Health Assessment Questionnaire-Disability Index and pain visual analogue scale, with sarilumab than adalimumab. Conclusion Sarilumab was associated with greater positive effects on bone remodelling and decreases in biomarkers of the acute-phase response, synovial inflammation and cardiovascular risk vs. adalimumab. High baseline concentrations of SAA, CRP and MMP-3 are predictive of clinical and patient-reported outcome responses to sarilumab treatment and prospective validation is warranted to confirm these results. Trial registration ClinicalTrials.gov, NCT02332590 . Registered on 5 January 2015http://link.springer.com/article/10.1186/s13075-020-02163-6Rheumatoid arthritisSarilumabBiomarkersBiologic disease-modifying antirheumatic drugCardiovascular riskBone remodelling |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Cem Gabay Gerd R. Burmester Vibeke Strand Jérôme Msihid Moshe Zilberstein Toshio Kimura Hubert van Hoogstraten Susan H. Boklage Jonathan Sadeh Neil M. H. Graham Anita Boyapati |
spellingShingle |
Cem Gabay Gerd R. Burmester Vibeke Strand Jérôme Msihid Moshe Zilberstein Toshio Kimura Hubert van Hoogstraten Susan H. Boklage Jonathan Sadeh Neil M. H. Graham Anita Boyapati Sarilumab and adalimumab differential effects on bone remodelling and cardiovascular risk biomarkers, and predictions of treatment outcomes Arthritis Research & Therapy Rheumatoid arthritis Sarilumab Biomarkers Biologic disease-modifying antirheumatic drug Cardiovascular risk Bone remodelling |
author_facet |
Cem Gabay Gerd R. Burmester Vibeke Strand Jérôme Msihid Moshe Zilberstein Toshio Kimura Hubert van Hoogstraten Susan H. Boklage Jonathan Sadeh Neil M. H. Graham Anita Boyapati |
author_sort |
Cem Gabay |
title |
Sarilumab and adalimumab differential effects on bone remodelling and cardiovascular risk biomarkers, and predictions of treatment outcomes |
title_short |
Sarilumab and adalimumab differential effects on bone remodelling and cardiovascular risk biomarkers, and predictions of treatment outcomes |
title_full |
Sarilumab and adalimumab differential effects on bone remodelling and cardiovascular risk biomarkers, and predictions of treatment outcomes |
title_fullStr |
Sarilumab and adalimumab differential effects on bone remodelling and cardiovascular risk biomarkers, and predictions of treatment outcomes |
title_full_unstemmed |
Sarilumab and adalimumab differential effects on bone remodelling and cardiovascular risk biomarkers, and predictions of treatment outcomes |
title_sort |
sarilumab and adalimumab differential effects on bone remodelling and cardiovascular risk biomarkers, and predictions of treatment outcomes |
publisher |
BMC |
series |
Arthritis Research & Therapy |
issn |
1478-6362 |
publishDate |
2020-04-01 |
description |
Abstract Background Interleukin-6 (IL-6) is a pleiotropic cytokine that plays a key role in the pathogenesis of rheumatoid arthritis. Sarilumab is a human monoclonal antibody that binds membrane-bound and soluble IL-6 receptor-α to inhibit IL-6 signalling. The aim of this study was to compare the effects of sarilumab and adalimumab (a tumour necrosis factor alpha inhibitor) monotherapy on levels of circulating biomarkers associated with the acute-phase response, bone remodelling, atherothrombosis, anaemia of chronic disease and markers purported to reflect synovial lymphoid and myeloid cell infiltrates, as well as the potential of these biomarkers to differentially predict clinical and patient-reported outcomes with sarilumab vs. adalimumab. Methods In this post hoc analysis, serum samples were analysed at baseline and prespecified post-treatment timepoints up to week 24 in adults with moderate-to-severe active rheumatoid arthritis intolerant of or inadequate responders to methotrexate from the MONARCH trial (NCT02332590). Results Greater reductions in C-reactive protein (CRP; − 94.0% vs. –24.0%), serum amyloid A (SAA; − 83.2% vs. –17.4%), total receptor activator of nuclear factor-κB ligand (RANKL; − 18.3% vs. 10.5%) and lipoprotein (a) (− 41.0% vs. –2.8%) were observed at week 24 with sarilumab vs. adalimumab, respectively (adjusted p < 0.0001). Greater increases in procollagen type 1 N-terminal propeptide (P1NP) were observed with sarilumab vs. adalimumab at week 24 (22.8% vs. 6.2%, p = 0.027). Patients with high baseline SAA, CRP and matrix metalloproteinase-3 (MMP-3) were more likely to achieve clinical efficacy, including American College of Rheumatology 20% improvement criteria and Disease Activity Score (28 joints)-CRP < 3.2, and report improvements in patient-reported outcomes, including Health Assessment Questionnaire-Disability Index and pain visual analogue scale, with sarilumab than adalimumab. Conclusion Sarilumab was associated with greater positive effects on bone remodelling and decreases in biomarkers of the acute-phase response, synovial inflammation and cardiovascular risk vs. adalimumab. High baseline concentrations of SAA, CRP and MMP-3 are predictive of clinical and patient-reported outcome responses to sarilumab treatment and prospective validation is warranted to confirm these results. Trial registration ClinicalTrials.gov, NCT02332590 . Registered on 5 January 2015 |
topic |
Rheumatoid arthritis Sarilumab Biomarkers Biologic disease-modifying antirheumatic drug Cardiovascular risk Bone remodelling |
url |
http://link.springer.com/article/10.1186/s13075-020-02163-6 |
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