Routine Hydroxychloroquine Blood Concentration Measurement in Systemic Lupus Erythematosus Reaches Adulthood
Bibliographic record
Abstract
The benefits of hydroxychloroquine (HCQ) treatment in patients with systemic lupus erythematosus (SLE) are now clearly recognized and it has been highly recommended that all patients with SLE should be prescribed this drug1. One less well-known benefit of HCQ is related to its pharmacokinetic properties (i.e., its long half-life) and to the availability of a blood assay to measure its blood concentration. Indeed, HCQ and its metabolite levels can be quantified by high performance liquid chromatography, which is available in many centers because this type of equipment is required to monitor other drugs (antidepressants, tyrosine kinase inhibitors, antibiotics, etc.). Methods of dosage may vary slightly, but for reasons of sensitivity and reproducibility, blood HCQ concentrations ([HCQ]) should be measured in whole blood (minimum 1 ml blood sampled in EDTA or in lithium heparinate tubs). In the 1980s, Tett, et al first described this method and studied the importance of [HCQ] measurement in patients with rheumatoid arthritis (RA). They first showed that there was a great variability in [HCQ] among individuals, including in healthy volunteers and adherent patients2,3. They also found a significant, although weak, correlation between [HCQ] and clinical efficacy in RA [corresponding to the so-called pharmacokinetic/pharmacodynamic (PK-PD) effect]3,4. These data were later confirmed by Munster, et al 5. When this blood measurement became available in our center in 2000, we decided to evaluate the PK-PD relationship of HCQ in patients with SLE. Among 143 unselected patients with SLE who were all receiving 400 mg/day of HCQ, the mean [HCQ] on day 0 was 1017 ± 532 ng/ml with more than a 10-fold range of drug concentrations found after similar doses6. We observed that low [HCQ] were associated with increased disease activity, and that low baseline [HCQ] … Address correspondence to Dr. N. Costedoat-Chalumeau, Hôpital Cochin, 75014, Paris, France. E-mail: nathalie.costedoat{at}gmail.com
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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 | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".