ArticleJournal of Crohn's & colitis2025
HLA-DQA1*05 Associates With Anti-Tumor Necrosis Factor Immunogenicity and Low Adalimumab Trough Concentrations in Inflammatory Bowel Disease Patients From the SERENE Ulcerative Colitis and Crohn's Disease Studies.
Article in Journal of Crohn's & colitis, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 10 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Multicenter, Randomized, Double-Blind Study to Evaluate Higher Versus Standard Adalimumab Dosing Regimens for Induction and Maintenance Therapy in Subjects With Moderately to Severely Active Crohn's Disease and Evidence of Mucosal Ulceration
A Double-Blind, Randomized, Multicenter Study of Higher Versus Standard Adalimumab Dosing Regimens for Induction and Maintenance Therapy in Subjects With Moderately to Severely Active Ulcerative Colitis
Who cites it
10 citing papers in PubMed.
- Rheumatoid factor production is genetically and molecularly distinct from rheumatoid arthritis.The Journal of clinical investigation · 2026Article
- External validation of population pharmacokinetic models of adalimumab in adult patients with inflammatory bowel disease: towards model-informed precision dosing.Journal of pharmacokinetics and pharmacodynamics · 2026Article
- HLA-DQA1*05:01 and DQA1*05:05 inform choice of anti-tumor necrosis factor and concomitant use of immunomodulators in patients with inflammatory bowel disease.Journal of Crohn's & colitis · 2025Article
- Article
- Molecular Insight into the Role of HLA Genotypes in Immunogenicity and Secondary Refractoriness to Anti-TNF Therapy in IBD Patients.International journal of molecular sciences · 2025Review
- Association of the HLA-DQA1*05 Allelic Gene Variants with Immunogenicity to Anti-TNF therapeutics-Important Differences Between Infliximab and Adalimumab.Journal of Crohn's & colitis · 2025Article
- Pharmacogenomics of TNF inhibitors.Frontiers in immunology · 2025Review
- Predicting resistance to biological therapy using human leukocyte antigen genes in patients with inflammatory bowel disease.Therapeutic advances in gastroenterology · 2025Article
- Identifying Genetic Factors Influencing the Development of Anti-Drug Antibodies in Inflammatory Bowel Disease: A Scoping Review.Journal of inflammation research · 2025Review
- MAPPs assays for non-clinical immunogenicity risk assessment: best practices recommended by the European immunogenicity platform.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
BACKGROUND AND
aimsAnti-tumor necrosis factor (anti-TNF) therapies are commonly prescribed treatments for Crohn's disease (CD) and ulcerative colitis (UC). Many patients treated with anti-TNF therapy eventually develop anti-drug antibodies (ADAs). Understanding the factors associated with immunogenicity in anti-TNF-treated patients can help guide treatment. The Humira SERENE studies were Phase 3 trials investigating adalimumab induction regimens in CD and UC patients.
methodsWe imputed alleles for 7 HLA genes in 1100 patients from the SERENE CD and SERENE UC trials. We then tested these alleles for association with time to immunogenicity. Subsequently, we tested loci significantly associated with immunogenicity for their association with patients who had consistently low drug serum concentrations.
resultsThis study replicated the association of HLA-DQA1*05 with time to immunogenicity (hazard ratio [HR] 1.42, p = 2.22E-06). Specifically, HLA-DQA1*05:05 was strongly associated (HR 1.76, p = 2.02E-10) and we detected a novel association represented by HLA-DRB1*01:02 (HR 3.16, p = 2.92E-07). Carriage of HLA-DQA1*05:05 and HLA-DRB1*01:02 was associated with patients who experienced consistently low adalimumab trough concentrations (HLA-DQA1*05:05: odds ratio [OR] 1.98, p = 0.0049; HLA DRB1*01:02: OR 7.06, p = 7.44E-05).
conclusionsWe found a significant association between alleles at genes in the human HLA locus and the formation of adalimumab immunogenicity and low adalimumab drug serum concentrations in large clinical studies of CD and UC patients. This work extends previous findings in CD to UC and directly shows a genetic association in patients with low drug concentrations. This work builds on existing literature to suggest that genetic screening could be a useful tool for clinicians concerned with patient anti-TNF immunogenicity. CLINICAL TRIAL REGISTRATION NUMBERS: SERENE CD (NCT02065570), SERENE UC (NCT02065622).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.