Early changes in blood-based joint tissue destruction biomarkers are predictive of response to tocilizumab in the LITHE study

Arthritis Research & Therapy
Anne C Bay-JensenM A Karsdal

Abstract

Rheumatoid arthritis (RA) is characterized by gradual joint destruction. Tocilizumab (TCZ) significantly suppresses symptoms, however not all patients are protected from joint damage. We investigated whether early measurement of specific biomarkers could predict early joint protection response to tocilizumab. Serum biomarkers (CRPM, VICM, C1M, C2M, C3M (MMP-degraded CRP, vimentin type I, II and III collagen), CTX-I/OC (bone turnover), and CRP) were measured in 740 RA patients (the LITHE study) treated with Placebo, or 4 or 8 mg/kg TCZ. Early responders were those with ≥20 % improvement in SJC or TJC by week 16. The biomarkers' predictability of response was investigated by AUROC and classification regression tree analysis. The best biomarker predictability for identification of TCZ responders were; baseline CTX-I/OC (AUC 0.66, p = 0.0005) and changes in C1M (AUC 0.67, p = 0.0072), C2M (AUC 0.72, p = 0.0002), C3M (AUC 0.63, p = 0.018) and the combination of biomarkers (AUC 0.81, p = 0.0025). Patients with high bone turnover (CTX-I/OC) and low C2M were 6.8-fold (p = 0.003) more likely to have an early response to TCZ. This enhanced pharmacodynamic (PD) response enabled identification of early responders with a superior TCZ clinic...Continue Reading

References

Oct 5, 2001·Seminars in Liver Disease·D SchuppanE G Hahn
May 8, 2003·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·P GarneroJ M Delaissé
Sep 10, 2004·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Robert ReckerRobert Heaney
May 26, 2006·The New England Journal of Medicine·Ego Seeman, Pierre D Delmas
Aug 17, 2006·European Journal of Clinical Pharmacology·D J LeemingL B Tankó
Aug 26, 2006·Nature Clinical Practice. Rheumatology·Georg SchettJosef S Smolen
Jan 24, 2007·Nature Medicine·Danielle DiarraGeorg Schett
Aug 5, 2008·Clinical Chemistry·Aurélie ClaudonPatrick Garnero
Apr 29, 2009·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·M A KarsdalC Christiansen
Oct 13, 2011·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·Dj LeemingMa Karsdal
Nov 9, 2012·Annals of the Rheumatic Diseases·Josef S Smolen, Daniel Aletaha
Jun 1, 2013·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·Morten A KarsdalClaus Christiansen
Aug 13, 2013·Seminars in Arthritis and Rheumatism·Anne C Bay-JensenMorten A Karsdal
Aug 16, 2013·Arthritis Research & Therapy·Anne Sofie SiebuhrMorten A Karsdal
Jan 29, 2014·Arthritis Care & Research·Morten A KarsdalAdam Platt

❮ Previous
Next ❯

Citations

Apr 11, 2018·Arthritis Research & Therapy·Henrik LöfvallChristian S Thudium
Apr 19, 2018·Arthritis & Rheumatology·Cecilie F Kjelgaard-PetersenAnne-C Bay-Jensen
Aug 29, 2018·Equine Veterinary Journal·A MitchellA E Watts
Nov 30, 2020·BMC Musculoskeletal Disorders·Christian S ThudiumMorten A Karsdal
Dec 11, 2020·Joint, Bone, Spine : Revue Du Rhumatisme·Guillermo Carvajal AlegriaYves Renaudineau
Mar 31, 2021·Expert Review of Proteomics·Anne C Bay-JensenClaus H Nielsen

❮ Previous
Next ❯

Methods Mentioned

BETA
ELISA

Clinical Trials Mentioned

NCT00106535

Software Mentioned

RADIATE
LITHE
Softmax Pro®
MedCalc

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.