Genetic Markers May Predict TNF Inhibitor Response in RA

TOPLINE:

Genetic markers, specifically tumor necrosis factor alpha receptor 2 (TNFR2) gene polymorphisms, may predict response to TNF inhibitor therapy in patients with rheumatoid arthritis (RA). This approach could optimize treatment and improve patient outcomes.

METHODOLOGY:

• The study aimed to determine if TNFR2 gene polymorphisms could serve as biomarkers for treatment responsiveness to TNF inhibitors.
• It included 52 adult patients with RA (average age, 57.4 years; mean body mass index, 31.4; 65% women; 80% Caucasian) who had a mean disease duration of 8.9 years and started treatment with a single TNF inhibitor (infliximab, adalimumab, etanercept, golimumab, or certolizumab pegol).
• TNFR2-M (methionine) and TNFR2-R(arginine) gene polymorphisms were identified using genomic DNA isolated from patients’ blood samples to determine M/M, M/R, or R/R genotypes.
• The primary outcome was nonresponse to TNF inhibitors, defined as discontinuation of medication in
• The relationship between TNF inhibitor responsiveness and TNFR2 gene polymorphisms was analyzed using univariable logistic regression.

TAKEAWAY:

• Genomic DNA analysis revealed that 28 patients were homozygous for methionine, 22 were heterozygous, and two were homozygous for arginine.
• Of these, 96.4% of patients with the M/M genotype were responders to TNF inhibitors, whereas 75% of those with the M/R genotype and 50% with the R/R genotype were responders.
• Patients with the M/M genotype had approximately 10 times higher odds of responding to TNF inhibitors than those with the M/R and R/R genotypes (odds ratio, 10.12; P = .04).

IN PRACTICE:

“Identifying predictors for nonresponsiveness to TNF antagonists based on TNFR2 gene polymorphisms may become a valuable tool for personalized medicine, allowing for a more specific TNFi therapy in RA patients,” the authors wrote. “Given that TNFi therapy is used for many autoimmune conditions beyond RA, this genotyping could potentially serve as a useful framework for personalized treatment strategies in other autoimmune diseases to delay or reduce disease progression overall.”

SOURCE:

This study was led by Elaine Husni, MD, MPH, Lerner Research Institute, Cleveland Clinic, Cleveland. It was published online on November 7, 2024, in Seminars in Arthritis and Rheumatism and presented as a poster at American College of Rheumatology (ACR) 2024 Annual Meeting.

LIMITATIONS:

This study’s sample size was relatively small.

DISCLOSURES:

This study was supported by the Arthritis Foundation and in part by the National Institutes of Health. No relevant conflicts of interest were disclosed by the authors.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.