Genetic biomarkers are sought to personalize treatment of patients with rheumatoid arthritis (RA), given their variable response to TNF inhibitors (TNFi). However, no genetic biomaker is yet sufficiently validated. Here, we report a validation study of 18 previously reported genetic biomarkers, including 11 from GWAS of response to TNFi. The validation was attempted in 581 patients with RA that had not been treated with biologic antirheumatic drugs previously. Their response to TNFi was evaluated at 3, 6 and 12 months in two ways: change in the DAS28 measure of disease activity, and according to the EULAR criteria for response to antirheumatic drugs. Association of these parameters with the genotypes, obtained by PCR amplification followed by single-base extension, was tested with regression analysis. These analyses were adjusted for baseline DAS28, sex, and the specific TNFi. However, none of the proposed biomarkers was validated, as none showed association with response to TNFi in our study, even at the time of assessment and with the outcome that showed the most significant result in previous studies. These negative results are notable because this was the first independent validation study for 12 of the biomarkers, and because they indicate that prudence is needed in the interpretation of the proposed biomarkers of response to TNFi even when they are supported by very low p values. The results also emphasize the requirement of independent replication for validation, and the need to search protocols that could increase reproducibility of the biomarkers of response to TNFi.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937760 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0196793 | PLOS |
Publication Analysis
Top Keywords
Similar Publications
Expert Clinical Management of Inflammatory Immune-Related Arthritis in Patients with Cancer Receiving Immune Checkpoint Inhibitors.
J Immunother Precis Oncol
February 2025
Department of Health Services and Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Introduction: Treatment guidelines for immune-related inflammatory arthritis (irAE-IA) in patients with cancer receiving immune checkpoint inhibitors (ICIs) are vague with respect to the use of specific agents. Patients are usually referred to rheumatologists for treatment. We conducted a survey of expert rheumatologists to determine current practices.
View Article and Find Full Text PDFConstruct validity and responsiveness of ASAS Health Index assessed in two longitudinal studies of tumour necrosis factor alpha inhibitor initiation and dose reduction in patients with axial spondyloarthritis.
RMD Open
December 2024
Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Centre for Head and Orthopaedics, Rigshospitalet, Copenhagen, Denmark.
Background: The Assessment of SpondyloArthritis international Society Health Index (ASAS HI) is a novel questionnaire of global functioning for patients with axial spondyloarthritis (SpA).
Objective: The objective was to assess the construct validity, discriminatory ability and responsiveness of ASAS HI in relation to patient-reported outcome measures (PROMs), MRI and radiography.
Methods: Data from two longitudinal studies with tumour necrosis factor inhibitor (TNFi) initiation (novel MRI And biomarkers in Golimumab-treated patients with axial spondyloarthritis (MANGO): n=45) respectively tapering (Dose adjustment of Biological treatment in patients with SpA (DOBIS): n=106) were used.
Age and biologic survival in patients with moderate-to-severe psoriasis: A cohort study from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR).
Br J Dermatol
January 2025
Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, The University of Manchester, Manchester, UK.
Background: The current management of psoriasis does not differentiate between young and old patients in selecting the safest and/or most effective biologic.
Objectives: To explore the effect of age at treatment initiation in response to biologics in patients with moderate-to-severe psoriasis in the UK and Eire.
Methods: Data from patients registering to the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) from 2007-2024 on first course of Tumour Necrosis Factor (TNF), interleukin (IL) 12/13, IL-17 and IL-23 inhibitors (i) with at least 6 months' follow-up were included.
Predictors of response to bDMARDs and tsDMARDs in psoriatic arthritis: a pilot study on the role of musculoskeletal ultrasound.
Front Med (Lausanne)
December 2024
Rheumatology Unit, Department of Medicine-DIMED, University - Padova University Hospital, Padua, Italy.
Objectives: This pilot study aimed to identify early predictors of drug retention in patients with clinically active peripheral psoriatic arthritis who initiated or switched to therapy with biologic and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs).
Methods: Clinical and ultrasound assessments were conducted at baseline (t0) and subsequently at 1 (t1), 3 (t3), and 6 (t6) months. Ultrasound evaluations targeted joints/entheses according to PsASon-Score13 and the most clinically involved joint/enthesis/tendon or the two most clinically involved joints/entheses/tendons (MIJET and 2MIJET).
Background: Axial Spondyloarthritis (axSpA) is a chronic inflammatory rheumatic condition affecting the axial skeleton, leading to pain, stiffness, and fatigue. While biologic therapies have improved clinical management, many patients experience partial or no responses, resulting in delays in disease control. Additionally, the risk of adverse events and increased costs remains a concern.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!