Genetic Polymorphisms Predict Response to Anti-TNF Treatment in Crohnʼs Disease
Bibliographic record
Abstract
Introduction: Anti-tumor necrosis factor-α therapy (anti-TNF Tx) is an important treatment for Crohn's disease (CD). However, a significant proportion of CD patients treated with anti-TNF Tx do not improve clinically. Predicting treatment response or failure is important both clinically and economically. Methods: CD patients were recruited from a university digestive disease practice. We included consecutive CD patients who received anti-TNF Tx, who had available medical records on treatment duration and efficacy, and for whom genomic DNA was available. Patients with allergic reactions were excluded. CD patients were grouped as “ever-responders” if they had a response to treatment or as “non-responders.” Seven single nucleotide polymorphisms (SNPs) linked with either CD and/or anti-TNF Tx were assessed in patient DNA samples: ATG16L1 (rs10210302, T300A rs2241880), Fas Ligand (-843 rs763110), IBD5 (rs2522057), FCGR 3A (rs396991), TNF (-308 rs1800629, -238 rs361525). Results: A total of 121 patients were included: 21 were non-responders to anti-TNF Tx and 100 were ever-responders. Fas ligand SNP genotype frequencies, TNF gene -308 SNP genotype frequencies, and the combination of these were significantly different between non-responders and ever-responders based on multivariable analysis controlling for Montreal disease behavior and perianal disease. The odds of a patient with a Fas ligand CC genotype being a non-responder were four-fold higher as compared to a TC or TT genotype (p=0.009, OR 4.30 CI 1.45-12.80). The presence of the A (minor) TNF gene -308 allele correlated with a three-fold higher odds of being a non-responder (p=0.049, OR 2.88 CI 1.01-8.22). Patients with the combination of the Fas ligand CC genotype and the TNF -308 A allele had nearly fivefold higher odds of being a non-responder (p=0.015, OR 4.76 CI 1.35-16.77). No difference was observed for the remaining SNPs. The Fas ligand CC genotype was present in 37% of patients, while the TNF -308 A allele was present in 29% of patients. Conclusion: In CD patients, both the Fas ligand rs763110 and the TNF -308 rs1800629 SNPs are highly associated with response to anti-TNF Tx. SNP genotyping utilizing DNA obtained from peripheral blood, used together with assessment of clinical disease behavior, may help select patients most likely to benefit from anti-TNF Tx and permit efficient and cost-effective treatment by avoiding expensive and morbid therapy that is likely to fail.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".