C‐Reactive Protein and Neutrophil‐To‐Lymphocyte Ratio: Can They Be Used Interchangeably in Tracking Clozapine‐Related Inflammation?
Bibliographic record
Abstract
BACKGROUND: Clozapine initiation often triggers inflammatory responses that can alter metabolism via Cytochrome P450 1A2 (CYP1A2) suppression. Although C-reactive protein (CRP) is the recommended marker, it may be unavailable in community settings. Neutrophil-to-lymphocyte ratio (NLR), routinely measured, could serve as a surrogate, though its value in detecting clozapine-related inflammation and metabolic changes remains unclear. AIMS: This study aimed to assess the relationship between CRP and NLR in individuals treated with clozapine, evaluate whether NLR can act as a proxy for elevated CRP (> 5 mg/L), and determine whether NLR, like CRP, explains variability in clozapine metabolism (concentration to dose (C/D) ratios) after adjusting for covariates. METHODS: We performed a retrospective cohort study of clozapine-treated inpatients at the British Columbia Psychosis Program (2012-2021). Patients with clozapine levels and matched complete blood counts (CBCs) (±7 days) were included, with CRP added when available. Multivariate mixed models assessed associations between CRP, NLR, and clozapine C/D ratios, while receiver operating characteristic (ROC) analyses evaluated NLR as a proxy for elevated CRP. RESULTS: Among 150 patients, 760 clozapine serum/CBC pairs and 212 CRP measurements met eligibility criteria. NLR was modestly associated with CRP (estimate = 0.027, p < 0.001). ROC analysis indicated that NLR had limited predictive utility, with an area under the curve (AUC) of 0.640 for detecting CRP > 5 mg/L. Subsequent analyses for higher CRP thresholds (> 10 and > 20 mg/L) produced comparable NLR AUC values of 0.621 and 0.669, respectively. Neutrophil count alone demonstrated marginally better performance but remained similarly limited in predictive value. In multivariate models, CRP but not NLR, was independently associated with clozapine C/D ratios. CONCLUSION: Our findings indicate that although NLR and other hematological indices are easily accessible and may provide some indication of inflammation, they cannot substitute for CRP in guiding clozapine titration decisions. Where CRP is unavailable, NLR > 3 may be cautiously informative, though CRP remains the preferred marker for early detection and dose adjustment to optimize tolerability, adherence, and safety during clozapine initiation.
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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 | 0.027 | 0.054 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.003 | 0.005 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.004 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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".