Association Between HLA genotypes and Oxcarbazepine-induced Cutaneous Adverse Drug Reactions: A Systematic Review and Meta-Analysis
Bibliographic record
Abstract
PURPOSE: To systematically review and quantitatively synthesize associations between HLA genotypes and oxcarbazepine-induced cutaneous adverse drug reactions (OXC-cADRs), including Stevens-Johnson syndrome (SJS) and maculopapular rash. METHODS: Studies investigating associations between HLA genotypes and OXC-cADRs were systematically searched irrespective of language, in PubMed, HuGENet (Human Genome Epidemiology Network), and the Cochrane Library from their inception until January, 2017. Inclusion criteria were studies investigating associations between HLA genotypes and OXC-cADRs that reported sufficient data for calculating the frequency of HLA genotype carriers among cases and controls. Overall odds ratios (ORs) with corresponding 95%CIs were calculated using a random-effects model to determine the association between HLA genotypes and OXC-cADRs. RESULTS: The initial searches identified 91 articles, of which 6 studies met the selection criteria. The studies included 229 patients with OXC-cADRs, 251 OXC-tolerant patients, and 2,358 participants from general populations of Han Chinese, Korean, and Thai ethnicities. Associations between HLA-B*1502 and OXC-induced SJS were found in both the general population [OR=30.2 (95%CI=3.45-264)] and in OXC-tolerant individuals [OR=26.4 (95%CI=7.98-87.6)]. An association between the HLA-B*1502 and OXC-induced maculopapular rash was found in the general population [OR=5.67 (95%CI=2.03-15.9)] while HLA-A*3101 also associated with OXC-induced maculopapular rash [overall OR=29.2 (95%CI=6.70-128)]. CONCLUSIONS: Strong associations between the HLA-B*1502 and OXC-cADRs (SJS and maculopapular rash) were found in both controls from general population and OXC-tolerant groups. There was also an association between HLA-B*3101 and OXC-induced maculopapular rash. For patient safety, genetic screening especially for HLA-B*1502 prior to OXC therapy at least in these closely related ethnicities is warranted. Further studies need to better define other ethnicities at risk and a wider range of MHC gene subtypes. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
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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 | 0.009 | 0.031 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.016 | 0.020 |
| Bibliometrics | 0.009 | 0.010 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".