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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Main Authors: 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
Format: Article
Language:English
Published: BMC 2020-04-01
Series:Arthritis Research & Therapy
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13075-020-02163-6
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spelling 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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