Artikel
Identifying differential predictive biomarkers for anti-interleukin-6 receptor and anti-tumor necrosis factor-α in active rheumatoid arthritis: MONARCH biomarker analyses
Suche in Medline nach
Autoren
Veröffentlicht: | 18. September 2024 |
---|
Gliederung
Text
Introduction: The identification of predictive and pharmacodynamic biomarkers to treatment response is of utmost importance to improve clinical and economic outcomes in patients with active rheumatoid arthritis (RA) [1]. Here, we identified blood-based predictive and pharmacodynamic biomarkers at different time points in patients with active RA treated with sarilumab (an anti-interleukin-6 receptor [anti-IL-6R]) or adalimumab (anti-tumour necrosis factor-α [anti-TNF-α]).
Methods: Blood samples from the MONARCH trial (NCT02332590) that evaluated safety and efficacy of anti-IL-6R vs anti-TNF-α monotherapies in patients with RA who were intolerant/inadequate responders to methotrexate were utilized in this study [2]. Predictive biomarkers to anti-IL-6R and anti-TNF-α treatments at baseline (before treatment initiation), and post-treatment Week 2 and pharmacodynamic biomarkers at post-treatment Week 2 and Week 24 were identified in serum (n=804 samples from 268 patients) using inflammation and cardiovascular-III multiplexed panels provided by Olink Proteomics. A Random Forest regression was performed to identify the relative importance of biomarkers in predicting treatment response while pharmacodynamic biomarkers were identified using a linear model (analysis of covariance). Change in gene expression levels in peripheral blood (n=522 samples from 261 patients) and different pathways deregulated by each treatment were assessed at Week 2 using RNA sequencing.
Results: We focused on relative prediction as absolute prediction performance of biomarkers to predict treatment response was limited. Despite this limitation, serum biomarkers most predictive to anti-IL-6R response were different from those of anti-TNF-α at different timepoints. Biomarkers predicting anti-IL-6R treatment response were correlated with innate immune activation and synovial inflammation, whereas biomarkers for anti-TNF-α response were mainly T-cell and neutrophil-related. Further, pharmacodynamic biomarkers for anti-IL-6R and anti-TNF-α were also not similar. RNA sequencing analysis confirmed that deregulated genes and pathways were different for both treatments.
Conclusion: The unbiased analysis of serum proteins in this study demonstrated a trend in difference in blood-based predictive biomarkers for anti-IL-6R and anti-TNF-α treatment response at different timepoints. Moreover, there were significant differences in pharmacodynamic biomarkers between two treatments. However, further studies with larger sample size are needed to confirm the findings. Results of this study support the concept of existence of different endotypes to different therapeutic classes in RA.
Acknowledgement: Medical writing assistance was provided by Arohi Sarang, M.Pharm. of Sanofi.
Disclosures: This study was funded by Sanofi.
IA, DM, AR, FF, EG, GT, MD, MK, MH, and NB are the employees of Sanofi and may hold stock and/or stock options in the company. VY and RB were the employees of Sanofi at the time of study conduct.
References
- 1.
- Chen SF, Yeh FC, Chen CY, Chang HY. Tailored therapeutic decision of rheumatoid arthritis using proteomic strategies: how to start and when to stop? Clin Proteomics. 2023 Jun 10;20(1):22. DOI: 10.1186/s12014-023-09411-2
- 2.
- Burmester GR, Lin Y, Patel R, van Adelsberg J, Mangan EK, Graham NM, van Hoogstraten H, Bauer D, Ignacio Vargas J, Lee EB. Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis (MONARCH): a randomised, double-blind, parallel-group phase III trial. Ann Rheum Dis. 2017 May;76(5):840-7. DOI: 10.1136/annrheumdis-2016-210310