Routine Hydroxychloroquine Blood Concentration Measurement in Systemic Lupus Erythematosus Reaches Adulthood

Costédoat-Chalumeau, Nathalie; Guern, Véronique Le; Piette, Jean‐Charles

doi:10.3899/jrheum.151094

Cited by 20 publications

(23 citation statements)

References 15 publications

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“…Dosages of HCQ and LEF were chosen based on serum levels seen in patients treated with the usual dosage of these drugs, with the highest concentration in vitro set as the highest concentration observed in vivo and subsequent testing of lower concentrations. With respect to HCQ, studies in SLE patients suggest a minimum effective blood concentration of 500 ng/ml (1.15 μM) [33], others claim that a minimum of 1000 ng/ml (2.3 μM) is required for therapeutic efficacy [33,34]. Our data show that at 3.3 μM HCQ in vitro robustly inhibits B cell activity, IFN-α and to a lesser extent CXCL13 production.…”

Section: Discussionmentioning

confidence: 52%

“…Therefore, 100 μM was chosen as the highest concentration. Studies in SLE patients suggest a minimum effective blood concentration of 500 ng/ml (1.15 μM) of HCQ, however others claim that a minimum of 1000 ng/ml (2.3 μM) is required for therapeutic efficacy [33,34]. Therefore, the optimal therapeutic range of HCQ remains to be determined [33].…”

Section: Hcq and Lef Distinctly Inhibit Lymphocyte Proliferation Cytmentioning

confidence: 99%

“…Therefore, the optimal therapeutic range of HCQ remains to be determined [33]. However, a great variability is seen in serum HCQ concentration among individuals, more than a 10-fold range of drug concentrations was found in patients all receiving similar doses [34]. Therefore, a concentration of 4300 ng/ml (this corresponds to 10 μM) was chosen as the highest condition.…”

Section: Hcq and Lef Distinctly Inhibit Lymphocyte Proliferation Cytmentioning

confidence: 99%

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Additive immunosuppressive effect of leflunomide and hydroxychloroquine supports rationale for combination therapy for Sjögren’s syndrome

Heijden

Hartgring

Kruize

et al. 2019

Expert Review of Clinical Immunology

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Objective: Effective treatment for primary Sjögren's syndrome (pSS) is not available. pSS immunopathology involves a variety of immune-cells and dysregulated pathways; targeting several pathways instead of only one could therefore be effective. Treatment with leflunomide (LEF) and hydroxychloroquine (HCQ) might be successful given their unique immunosuppressive properties. We aimed to study the in vitro effects of LEF, HCQ and their combination on T-and B-cell proliferation, cytokine and immunoglobulin production by activated PBMCs. Methods: PBMCs of six healthy individuals and nine pSS patients were stimulated with superantigen and TLR9 agonist to mimic the hallmark features. LEF, HCQ and their combinations were tested at clinically observed concentrations and proliferation, cytokine and immunoglobulin production were measured. Results: TCR/TLR9 activation of PBMCs induced strong proliferation of T and B-cells and production of CXCL13, IFN-α, IFN-γ, IgG and IgM. LEF dose-dependently inhibited all measured parameters, where HCQ potently and dose-dependently decreased B cell proliferation, CXCL13, IFN-α, IgG and IgM production. At different concentration combinations, HCQ and LEF inhibited several immune hallmark features more potently than each single compound. Conclusion: A combination of LEF and HCQ at clinically applicable concentrations additively inhibits immune activation, supporting a potential implementation of this drug combination in pSS treatment.

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Section: Discussionmentioning

confidence: 52%

Section: Hcq and Lef Distinctly Inhibit Lymphocyte Proliferation Cytmentioning

confidence: 99%

Section: Hcq and Lef Distinctly Inhibit Lymphocyte Proliferation Cytmentioning

confidence: 99%

See 1 more Smart Citation

Additive immunosuppressive effect of leflunomide and hydroxychloroquine supports rationale for combination therapy for Sjögren’s syndrome

Heijden

Hartgring

Kruize

et al. 2019

Expert Review of Clinical Immunology

View full text Add to dashboard Cite

show abstract

“…MPR and PDC also exclude patients who filled their first prescription, but then failed to fill their second prescription, which will likely underestimate the rate of secondary medication adherence. More recent studies have demonstrated the utility of HCQ blood level to monitor medication adherence and correlation with SLE flare 27,28,29 . Future studies on medication adherence in HCQ can be strengthened by measuring blood level rather than using MPR.…”

Section: Discussionmentioning

confidence: 99%

Understanding Nonadherence with Hydroxychloroquine Therapy in Systemic Lupus Erythematosus

Liu

Fevrier²,

Goldfien³

et al. 2019

J Rheumatol

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Objective.Hydroxychloroquine (HCQ) is a cornerstone to managing systemic lupus erythematosus (SLE), yet adherence to medication is poor. We sought to measure the association of adherence with 5 “dimensions of adherence” as articulated by the World Health Organization for chronic conditions: the patient’s socioeconomic status, and patient-, condition-, therapy-, and healthcare system–related factors. Our longterm goal is to generate evidence to design effective interventions to increase adherence.Methods.The retrospective cohort study included Kaiser Permanente Northern California patients ≥ 18 years old during 2006–2014, with SLE and ≥ 2 consecutive prescriptions for HCQ. Adherence was calculated from the medication possession ratio and dichotomized as < 80% versus ≥ 80%. Predictor variables were obtained from the electronic medical record and census data. We used multivariable logistic regression to estimate adjusted OR and 95% CI.Results.The study included 1956 patients. Only 58% of patients had adherence ≥ 80%. In adjusted analyses, socioeconomic variables did not predict adherence. Increasing age (65–89 yrs compared with ≤ 39 yrs: OR 1.44, 95% CI 1.07–1.93), white race (p < 0.05), and the number of rheumatology visits in the year before baseline (≥ 3 compared with 0 or 1: OR 1.47, 95% CI 1.18–1.83) were positively associated with adherence. The rheumatologist and medical center providing care were not associated with adherence.Conclusion.At our setting, as in other settings, about half of patients with SLE were not adherent to HCQ therapy. Differences in adherence by race/ethnicity suggest the possibility of using tailored interventions to increase adherence. Qualitative research is needed to elucidate patient preferences for adherence support.

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“…In a similar fashion, a prospective study of 300 patients taking HCQ found that actual body weight strongly correlated with blood levels of HCQ 7 , a finding that is corroborated by the study by Durcan, et al 4 . As stated in the editorial, no study has yet definitively linked high blood concentration of HCQ to retinal toxicity 8 , but higher doses and longer durations of therapy have been linked to risk for HCQ retinopathy 1,9 , suggesting that cumulative dose may be a significant risk factor for HCQ retinopathy.…”

Section: To the Editormentioning

confidence: 99%

Retinopathy in the Era of Routine Hydroxychloroquine Monitoring

2016

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Routine Hydroxychloroquine Blood Concentration Measurement in Systemic Lupus Erythematosus Reaches Adulthood

Cited by 20 publications

References 15 publications

Additive immunosuppressive effect of leflunomide and hydroxychloroquine supports rationale for combination therapy for Sjögren’s syndrome

Additive immunosuppressive effect of leflunomide and hydroxychloroquine supports rationale for combination therapy for Sjögren’s syndrome

Understanding Nonadherence with Hydroxychloroquine Therapy in Systemic Lupus Erythematosus

Retinopathy in the Era of Routine Hydroxychloroquine Monitoring

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