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

被引：23

作者：

Blanchet, Benoit ^{[1
,2
]}

Jallouli, Moez ^{[3
]}

Allard, Marie ^{[4
,5
]}

Ghillani-Dalbin, Pascale ^{[6
]}

Galicier, Lionel ^{[7
,8
]}

Aumaitre, Olivier ^{[9
,10
]}

Chasset, Francois ^{[11
,12
]}

Le Guern, Veronique ^{[13
]}

Liote, Frederic ^{[14
,15
]}

Smail, Amar ^{[16
]}

Limal, Nicolas ^{[17
]}

Perard, Laurent ^{[18
]}

Desmurs-Clavel, Helene ^{[19
]}

Le Thi Huong, Du ^{[11
,20
]}

Asli, Bouchra ^{[7
,8
]}

Kahn, Jean-Emmanuel ^{[21
]}

Sailler, Laurent ^{[22
,23
]}

Ackermann, Felix ^{[24
]}

Papo, Thomas ^{[4
,5
]}

Sacre, Karim ^{[4
,5
]}

Fain, Olivier ^{[25
]}

Stirnemann, Jerome ^{[26
]}

Cacoub, Patrice ^{[11
,27
]}

Leroux, Gaelle ^{[11
,27
]}

Cohen-Bittan, Judith ^{[28
]}

Sellam, Jeremie ^{[29
]}

Mariette, Xavier ^{[30
]}

Goulvestre, Claire ^{[31
]}

Hulot, Jean Sebastien ^{[32
]}

Amoura, Zahir ^{[11
,20
]}

Vidal, Michel ^{[1
,2
]}

Piette, Jean-Charles ^{[11
,27
]}

Jourde-Chiche, Noemie ^{[33
,34
]}

Costedoat-Chalumeau, Nathalie ^{[13
,35
,36
]}

机构：

[1] Hop Cochin, AP HP, Biol Medicament Toxicol, 27 Rue Faubourg St Jacques, F-75014 Paris, France

[2] Univ Paris 05, CNRS, PRES Sorbonne Paris Cite, INSERM,Fac Pharm,U1268,UMR8038, Paris, France

[3] Hop Hedi Chaker, Serv Med Interne, Sfax, Tunisia

[4] Univ Paris Diderot, Sorbonne Paris Cite, F-75205 Paris, France

[5] Hop Bichat Claude Bernard, AP HP, Serv Med Interne, 46 Rue Henri Huchard, F-75018 Paris, France

[6] Hop La Pitie Salpetriere, AP HP, Dept Immunol, 47-83 Blvd Hop, F-75651 Paris 13, France

[7] Univ Paris Diderot, Sorbonne Paris Cite, Paris, France

[8] Hop St Louis, AP HP, Serv Immunol Clin, 1 Ave Claude Vellefaux, F-75010 Paris, France

[9] Univ Clermont Ferrand, F-63003 Clermont Ferrand, France

[10] CHU Clermont Ferrand, Hop Gabriel Montpied, Serv Med Interne, 58 Rue Montalembert, F-63003 Clermont Ferrand 1, France

[11] Univ Paris 06, UPMC, Paris, France

[12] Hop Tenon, AP HP, Serv Dermatol Allergol, 4 Rue Chine, F-75020 Paris, France

[13] Hop Cochin, AP HP, Ctr Reference Malad Autoimmunes & Syst Rares, Serv Med Interne, 27 Rue Faubourg St Jacques, F-75014 Paris, France

[14] Univ Paris, F-75205 Paris, France

[15] Hop Lariboisiere, AP HP, Serv Rhumatol, DMU Locomot, 2 Rue Ambroise Pare, F-75010 Paris, France

[16] CHU Amiens, Hop Nord, Serv Med Interne, Pl Victor Pauchet, F-80000 Amiens, France

[17] Hop Henri Mondor, AP HP, Serv Med Interne, 51 Ave Marechal Tassigny, F-94000 Creteil, France

[18] Ctr Hosp St Joseph St Luc, Serv Med Interne, 20 Quai Claude Bernard, F-69007 Lyon, France

[19] Groupement Hosp Edouard Herriot, Hosp Civils Lyon, Serv Med Interne, 5 Pl dArsonval, F-69003 Lyon, France

[20] Hop La Pitie Salpetriere, AP HP, Ctr Reference Lupus Syst & Syndrome Antiphospholi, Serv Med Interne, 47-83 Blvd Hop, F-75651 Paris 13, France

[21] Univ Paris Saclay, Hop Ambroise Pare, Serv Med Interne, 9 Ave Charles Gaulle, F-92104 Boulogne, France

[22] Univ Paul Sabatier, Toulouse, France

[23] CHU Toulouse, Hop Purpan, Serv Med Interne, Pl Dr Baylac, F-31059 Toulouse, France

[24] Hop Foch, Serv Med Interne, F-92150 Suresnes, France

[25] Sorbonne Univ, Hop St Antoine, AP HP, Serv Med Interne, F-75012 Paris, France

[26] Hop Univ Geneve, Serv Med Interne Generale, Ave Gabrielle Perret Gentil 4, CH-1211 Geneva, Switzerland

[27] Hop La Pitie Salpetriere, AP HP, Ctr Reference Malad Autoimmunes & Syst Rares, Serv Med Interne 2, 47-83 Blvd Hop, F-75651 Paris 13, France

[28] Hop La Pitie Salpetriere, AP HP, Serv Geriatr, 47-83 Blvd Hop, F-75651 Paris 13, France

[29] Hop St Antoine, AP HP, Serv Rhumatol, 184 Rue Faubourg St Antoine, F-75012 Paris, France

[30] Univ Paris Sud, Hop Univ Paris Sud, AP HP, Serv Rhumatol,INSERM,UMR 1184, Paris, France

[31] Hop Cochin, AP HP, Serv Immunol Biol, 27 Rue Faubourg St Jacques, F-75014 Paris, France

[32] Paris Cardiovasc Res Ctr, INSERM, UMRS 970, Paris, France

[33] Aix Marseille Univ, INSERM 1263, C2VN, INRA 1260, Marseille, France

[34] AP HM, Ctr Nephrol & Transplantat Renale, Marseille, France

[35] Univ Paris 05, Paris, France

[36] INSERM, Ctr Epidemiol & Stat, Sorbonne Paris Cite CRESS, U 1153, Paris, France

来源：

ARTHRITIS RESEARCH & THERAPY | 2020年 / 22卷 / 01期

关键词：

Hydroxychloroquine; Systemic lupus erythematosus; Serum; Drug monitoring; Adherence; RHEUMATOID-ARTHRITIS; DRUGS;

D O I：

10.1186/s13075-020-02291-z

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页数：10

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