Dataset Information

Hydroxychloroquine levels in patients with systemic lupus erythematosus: whole blood is preferable but serum levels also detect non-adherence.

ABSTRACT:

Background

Hydroxychloroquine (HCQ) levels can be measured in both serum and whole blood. No cut-off point for non-adherence has been established in serum nor have these methods ever been compared. The aims of this study were to compare these two approaches and determine if serum HCQ cut-off points can be established to identify non-adherent patients.

Methods

HCQ levels were measured in serum and whole blood from 573 patients with systemic lupus erythematosus (SLE). The risk factors for active SLE (SLEDAI score > 4) were identified by multiple logistic regression. Serum HCQ levels were measured in 68 additional patients known to be non-adherent, i.e. with whole-blood HCQ < 200 ng/mL.

Results

The mean (± SD) HCQ levels were 469 ± 223 ng/mL in serum and 916 ± 449 ng/mL in whole blood. The mean ratio of serum/whole-blood HCQ levels was 0.53 ± 0.15. In the multivariate analysis, low whole-blood HCQ levels (P = 0.023), but not serum HCQ levels, were independently associated with active SLE. From the mean serum/whole-blood level ratio, a serum HCQ level of 106 ng/mL was extrapolated as the corresponding cut-off to identify non-adherent patients with a sensitivity of 0.87 (95% CI 0.76-0.94) and specificity of 0.89 (95% CI 0.72-0.98). All serum HCQ levels of patients with whole-blood HCQ below the detectable level (< 20 ng/mL) were also undetectable (< 20 ng/mL).

Conclusions

These data suggest that whole blood is better than serum for assessing the pharmacokinetic/pharmacodynamic relation of HCQ. Our results support the use of serum HCQ levels to assess non-adherence when whole blood is unavailable.

SUBMITTER: Blanchet B

PROVIDER: S-EPMC7517694 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Publications

Hydroxychloroquine levels in patients with systemic lupus erythematosus: whole blood is preferable but serum levels also detect non-adherence.

Blanchet Benoit B Jallouli Moez M Allard Marie M Ghillani-Dalbin Pascale P Galicier Lionel L Aumaître Olivier O Chasset François F Le Guern Véronique V Lioté Frédéric F Smail Amar A Limal Nicolas N Perard Laurent L Desmurs-Clavel Hélène H Le Thi Huong Du D Asli Bouchra B Kahn Jean-Emmanuel JE Sailler Laurent L Ackermann Félix F Papo Thomas T Sacré Karim K Fain Olivier O Stirnemann Jérôme J Cacoub Patrice P Leroux Gaelle G Cohen-Bittan Judith J Sellam Jérémie J Mariette Xavier X Goulvestre Claire C Hulot Jean Sébastien JS Amoura Zahir Z Vidal Michel M Piette Jean-Charles JC Jourde-Chiche Noémie N Costedoat-Chalumeau Nathalie N

Arthritis research & therapy 20200925 1

<h4>Background</h4>Hydroxychloroquine (HCQ) levels can be measured in both serum and whole blood. No cut-off point for non-adherence has been established in serum nor have these methods ever been compared. The aims of this study were to compare these two approaches and determine if serum HCQ cut-off points can be established to identify non-adherent patients.<h4>Methods</h4>HCQ levels were measured in serum and whole blood from 573 patients with systemic lupus erythematosus (SLE). The risk facto ...[more]

PMID: 32977856

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Project description:ImportanceSystemic lupus erythematosus (SLE) predisposes individuals to early cardiovascular (CV) events. While hydroxychloroquine is thought to mitigate CV risk factors, its protective role against CV events, particularly arterial ones, remains to be confirmed.ObjectiveTo evaluate the association between hydroxychloroquine and the risk of myocardial infarction (MI), stroke, and other thromboembolic events (OTEs) in patients with SLE.Design, setting, and participantsThis cohort study using a nested case-control design was conducted within the National French Healthcare Database (SNDS), which represents 99% of the French population, from 2010 to 2020. Participants were the cohort of all patients with SLE recorded in the SNDS. Patients with SLE experiencing CV events during the study period were the case group; those without CV events were controls. The analysis period was from February 2022 to September 2023.ExposuresHydroxychloroquine use within 365 days prior to the index date, defined as current (within 90 days), remote (91-365 days), or no exposure within the previous 365 days.Main outcomes and measuresOutcomes of interest were MI, stroke, and OTE, analyzed individually and as a composite outcome (primary analysis). Controls were matched to patients with CV events by age, sex, time since SLE onset and entry into the SNDS database, index date, prior antithrombotic and CV medication, chronic kidney disease, and hospitalization. Multivariable conditional logistic regression was performed using hydroxychloroquine exposure as the main independent variable.ResultsThe SLE cohort included 52 883 patients (mean [SD] age, 44.23 [16.09] years; 45 255 [86.6%] female; mean [SD] follow-up, 9.01 [2.51] years), including 1981 patients with eligible CV events and 16 892 matched control patients. There were 669 MI events, 916 stroke events, and 696 OTEs in the individual outcome studies. For current exposure to hydroxychloroquine, the adjusted odds were lower for composite CV events (odds ratio [OR], 0.63; 95% CI, 0.57-0.69) as well as for MI (OR, 0.72; 95% CI, 0.60-0.85), stroke (OR, 0.69; 95% CI, 0.60-0.81), and OTEs (OR, 0.58; 95% CI, 0.49-0.69) individually compared with no hydroxychloroquine exposure within 365 days.Conclusions and relevanceIn this nationwide cohort study of patients with SLE, a protective association was found between the current use of hydroxychloroquine and the occurrence of CV events, but not between remote use of hydroxychloroquine and CV outcomes, highlighting the value of continuous hydroxychloroquine treatment in patients with SLE.

Project description:ObjectivesUsing a representative sample of children with systemic lupus erythematosus (SLE) in the United States, we characterized prescription claim-based hydroxychloroquine and immunosuppressant adherence estimates and evaluated their concurrent and predictive validity.MethodsWe identified children ages 5-18 with SLE in the Truven Health MarketScan® Commercial and Medicaid claims databases (2013-2018). Among new users of hydroxychloroquine and immunosuppressant medications, we calculated proportion of days covered (PDC) over 365 days to estimate adherence by user group (mycophenolate, azathioprine, methotrexate, and any immunosuppressant use). Agreement between adherence estimates was evaluated with intraclass correlation coefficients (ICC) and kappa statistics. Separate negative binomial regression models were used to estimate associations between (a) hydroxychloroquine, (b) immunosuppressant, or (c) concurrent immunosuppressant/hydroxychloroquine non-adherence and subsequent hospitalizations, adjusted for baseline demographics, disease severity, and healthcare utilization.ResultsAmong 423 new hydroxychloroquine/immunosuppressant users, 63% were Medicaid recipients. Sufficient adherence (PDC≥80%) ranged from 33 to 45% for immunosuppressants vs. 51-52% for hydroxychloroquine. Agreement between hydroxychloroquine and immunosuppressant adherence was modest overall, but better for mycophenolate (ICC 0.55) than methotrexate (0.27). Hydroxychloroquine non-adherence was associated with a 2.9-fold higher incidence of subsequent hospitalizations (95% CI [1.2-7.1]), whereas immunosuppressant and concurrent non-adherence were associated with 5.9 [2.4-14.6] and 5.6-fold [2.0-15.5] increased incidence, respectively. Use of concurrent adherence improved upon estimation of hospitalization risk compared to hydroxychloroquine adherence, but not immunosuppressant adherence alone.ConclusionsHydroxychloroquine adherence is an imperfect proxy for adherence to other lupus medications among children with SLE, and therefore assessing immunosuppressant adherence concurrently adds value to hydroxychloroquine adherence assessments. Prescription claims-based immunosuppressant adherence measures are predictive of acute care utilization and may inform population management strategies.

Project description:Correlation between soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) concentration, VEGFR1 gene polymorphisms and systemic lupus erythematosus (SLE) risk remains unclear. The present case-control study comprised 254 SLE patients, 385 other rheumatic diseases patients and 390 healthy controls. Serum levels of sVEGFR-1 were detected by enzyme-linked immunosorbent assay. Seven VEGFR1 genetic variants (rs2296188, rs9943922, rs2296283, rs7324510, rs9554322, rs9582036, rs9554320) were genotyped by KASP. Serum levels of sVEGFR-1 were up-regulated in SLE and positively correlated with disease activity. Furthermore, serum sVEGFR-1 presented a distinctive elevation in SLE in comparison with other rheumatic diseases. Frequencies of allele T of rs2296283 and allele G of rs9554322 were significant lower in SLE patients (P = 0.003, P = 0.004). Frequencies of genotypes TT of rs2296188 and rs2296283 were declined in patients compared with healthy controls (P = 0.039, P = 0.033). CC genotype of rs7324510 and rs9582036 was negatively correlated with SLE risk (OR = 0.538, OR = 0.508). Distribution of GG, GC, GG + GC genotypes of rs9554322 were different between SLE patients and healthy controls (P = 0.027, P = 0.036, P = 0.010). Moreover, frequency of TC genotype of rs7324510 was higher in SLE patients with lupus headache (χ2 = 9.924, P = 0.039) and frequency of TC genotype of rs9943922 was lower in patients with cylindruriain (χ2 = 7.589, P = 0.026). Frequencies of allele C of rs7324510 and allele T of rs9943922 were decreased in SLE patients with cylindruria and hypocomplementemia, respectively (χ2 = 4.195, P = 0.041, χ2 = 3.971, P = 0.046). However, frequency of allele C of rs9554322 was increased in SLE patients with pyuria (χ2 = 11.702, P = 0.001). In addition, SLE patients carrying GG, GC, CC genotypes for rs9554322 had higher levels of serum sVEGFR-1. In conclusion, serum sVEGFR-1 was elevated in SLE patients and may be a disease marker. VEGFR1 gene polymorphisms related to risk of SLE in a Chinese Han population.

Dataset Information

Hydroxychloroquine levels in patients with systemic lupus erythematosus: whole blood is preferable but serum levels also detect non-adherence.

Background

Methods

Results

Conclusions

Publications

Hydroxychloroquine levels in patients with systemic lupus erythematosus: whole blood is preferable but serum levels also detect non-adherence.

Similar Datasets

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