Sarilumab and adalimumab differential effects on bone remodelling and cardiovascular risk biomarkers, and predictions of treatment outcomes
Open Access
- 7 April 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Arthritis Research & Therapy
- Vol. 22 (1), 1-11
- https://doi.org/10.1186/s13075-020-02163-6
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-alpha 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-kappa B 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.Funding Information
- Sanofi Genzyme
- Regeneron Pharmaceuticals
This publication has 26 references indexed in Scilit:
- Sarilumab Plus Methotrexate in Patients With Active Rheumatoid Arthritis and Inadequate Response to Methotrexate: Results of a Phase III StudyArthritis & Rheumatology, 2015
- IL-6 biology: implications for clinical targeting in rheumatic diseaseNature Reviews Rheumatology, 2014
- Cardiovascular risk in rheumatoid arthritis: recent advances in the understanding of the pivotal role of inflammation, risk predictors and the impact of treatmentRheumatology, 2014
- Synovial phenotypes in rheumatoid arthritis correlate with response to biologic therapeuticsArthritis Research & Therapy, 2014
- Comparative evaluation of the effects of treatment with tocilizumab and TNF-α inhibitors on serum hepcidin, anemia response and disease activity in rheumatoid arthritis patientsArthritis Research & Therapy, 2013
- Bone erosion in rheumatoid arthritis: mechanisms, diagnosis and treatmentNature Reviews Rheumatology, 2012
- Understanding the dynamics: pathways involved in the pathogenesis of rheumatoid arthritisRheumatology, 2012
- Bone Damage in Rheumatoid Arthritis: Mechanistic Insights and Approaches to PreventionRheumatic Disease Clinics of North America, 2010
- Cytokines in the pathogenesis of rheumatoid arthritisNature Reviews Immunology, 2007
- Patterns of cardiovascular risk in rheumatoid arthritisAnnals Of The Rheumatic Diseases, 2006