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Updated: Jan 8, 2026
Determination of the Relative Potency of an Anti-TNF Monoclonal Antibody mAb by Neutralizing TNF Using an In Vitro Bioanalytical Method
Published on: September 16, 2017
Clinical utility of pre-treatment four-digit-resolution HLA genotyping to guide anti-tumor necrosis factor choice and
Phoebe Hodges1,2, Christopher Roberts1,2, Miles Parkes3,4
1Department of Gastroenterology, Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom.
Background And Aims:
Immunogenicity and the development of an undetectable drug level is a modifiable cause of anti-tumor necrosis factor (anti-TNF) treatment failure. We modeled the clinical utility of pre-treatment HLA-DQA1*05:01 and HLA-DQA1*05:05 allele subtype testing to guide immunomodulator use in patients with Crohn's disease treated with an anti-TNF.
Methods:
The Personalised Anti-TNF Therapy in Crohn's Disease study is a UK-wide, prospective observational study of infliximab and adalimumab in anti-TNF-naïve patients with active Crohn's disease. Rates of drug-clearing antibody development, defined by the presence of anti-TNF antibodies and undetectable drug levels, were estimated using the Kaplan-Meier method. Genetic association tests were performed using Cox proportional hazards regression.
Results:
About 40% of participants carried an actionable HLA-DQA1*05 allele subtype. HLA-DQA1*05:01 (hazard ratio [HR] 1.87 [95% CI: 1.37-2.53], P < .0001) and HLA-DQA1*05:05 (HR 2.45 [95% CI: 1.32-4.54], P = .004) were the most significant allele subtypes associated with the development of drug-clearing antibodies in infliximab- and adalimumab-treated patients, respectively. Immunomodulator use increased the time to drug-clearing antibodies in all patients treated with infliximab. In adalimumab-treated patients, only individuals who carried the HLA-DQA1*05:05 allele subtype benefited from combination immunomodulator use with a number needed to treat of 4.6 (95% CI: 2.4-20.5) to prevent one episode of a drug-clearing antibody.
Discussion:
Pre-treatment four-digit HLA testing informs on anti-TNF treatment choice and immunomodulator use. In HLA-DQA1*05:01 carriers, adalimumab monotherapy should be used and infliximab avoided. In HLA-DQA1*05:05 carriers, infliximab or adalimumab can be used with a concomitant immunomodulator. In patients who do not carry either HLA-DQA1*05:01 or HLA-DQA1*05:05, adalimumab monotherapy or infliximab with a concomitant immunomodulator are recommended.
