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Genetic variant influences anti-TNF immunogenicity in Crohn’s
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A genetic variant carried by 40% of the population of Europe could explain why some patients with inflammatory bowel disease do not respond to anti-TNF therapy, according to study results.
Tariq Ahmad, DPhil, head of the IBD and Pharmacogenetics Research Group at the University of Exeter, and colleagues wrote that testing for the HLA-DQA1*05 allele could help physicians select the best treatments for patients and improve outcomes.
“We strongly believe that this type of research is essential to developing cost effective, treatment strategies for patients with inflammatory bowel disease,” he said in a press release.
Researchers performed a genome-wide association study to identify variants linked with the development of anti-drug antibody in a group of 1,240 biologic naive patients with Crohn’s disease starting Remicade (infliximab, Janssen) or Humira (adalimumab, AbbVie) therapy. They defined immunogenicity as an anti-drug antibody titer of at least 10 absorbance units (AU) per mL in a drug-tolerant enzyme-linked immunosorbent assay.
Ahmad and colleagues found that the HLA-DQA1*05 allele increased the rate of immunogenicity (HR = 1.9; 95% CI, 1.6–2.25). Patients treated with infliximab monotherapy who carried the HLA-DQA1*05 allele had the highest rates of immunogenicity at 1 year (92%), while patients without HLA-DQA1*05 on adalimumab combination therapy had the lowest rate at 1 year (10%).
Researchers found that the association was consistent in patients treated with adalimumab (HR = 1.89; 95% CI, 1.32–2.7) or infliximab (HR = 1.92; 95% CI, 1.57–2.33) and for patients treated with monotherapy (HR = 1.75; 95% CI, 1.37–2.22) and combination therapy (HR = 2.01; 95% CI, 1.57–2.58). They also confirmed the association in a replication cohort of 178 patients with IBD (HR = 2; 95% CI, 1.35–2.98).
“The future of Crohn's and Colitis treatment is personalized medicine, so the identification of a genetic marker that explains why anti-TNF drugs don't work for some people with Crohn's is highly significant,” Helen Terry, director of research at Crohn’s and Colitis UK, said in the release. “These results are extremely promising and with further research could lead to individualized treatment and better outcomes for the people living with these debilitating conditions.” – by Alex Young
Disclosure s: Ahmad reports receiving unrestricted research grants, advisory board fees, speaker honorariums and support to attend international meetings from AbbVie, Celltrion, Ferring, Hospira, Janssen, Merck, NAPP, Takeda and Tillotts. Please see the full study for all other authors’ relevant financial disclosures.
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