Association between severe non-adherence to hydroxychloroquine and SLE flares, damage, and mortality in 660 patients from the SLICC Inception Cohort

Yann Nguyen; Benoît Blanchet; Murray B Urowitz; John G Hanly; Caroline Gordon; Sang-Cheol  Bae; Juanita Romero-Diaz; Jorge Sanchez-Guerro; Ann E Clarke; Sasha Bernatsky; Daniel J Wallace; David Isenberg; Anisur Rahman; Joan T Merrill; Paul Fortin; Dafna Gladman; Ian N Bruce; Michelle Petri; Ellen Ginzler; Mary Anne Dooley; Rosalind Ramsey-Goldman; Susan Manzi; Andreas Jonsen; Graciela Alarcon; Ronald van Vollenhoven; Cynthia Aranow; Véronique  Le Guern; Meggan Mackay; Guillermo Ruiz-Irastorza; Sam Lim; Murat Inanc; KC Kalunian; Soren Jacobsen; Christine A Peschken; Diane L Kamen; Anca Askanase; Jill Buyon; Nathalie Costedoat-Chalumeau

doi:10.1002/art.42645

Association between severe non-adherence to hydroxychloroquine and SLE flares, damage, and mortality in 660 patients from the SLICC Inception Cohort

Yann Nguyen, Benoît Blanchet, Murray B Urowitz, John G Hanly, Caroline Gordon, Sang-Cheol Bae, Juanita Romero-Diaz, Jorge Sanchez-Guerro, Ann E Clarke, Sasha Bernatsky, Daniel J Wallace, David Isenberg, Anisur Rahman, Joan T Merrill, Paul Fortin, Dafna Gladman, Ian N Bruce, Michelle Petri, Ellen Ginzler, Mary Anne DooleyRosalind Ramsey-Goldman, Susan Manzi, Andreas Jonsen, Graciela Alarcon, Ronald van Vollenhoven, Cynthia Aranow, Véronique Le Guern, Meggan Mackay, Guillermo Ruiz-Irastorza, Sam Lim, Murat Inanc, KC Kalunian, Soren Jacobsen, Christine A Peschken, Diane L Kamen, Anca Askanase, Jill Buyon, Nathalie Costedoat-Chalumeau^*

^*Corresponding author for this work

Inflammation and Ageing

Research output: Contribution to journal › Article › peer-review

Abstract

Objectives. To assess the associations of severe non-adherence to HCQ, objectively assessed by HCQ serum levels, and risks of SLE flares, damage, and mortality over 5 years of follow-up.

Methods. The SLICC Inception Cohort is an international multicenter initiative (33 centers; 11 countries). Serum of patients prescribed HCQ for at least 3 months at enrollment were analyzed. Severe non-adherence was defined by a serum HCQ level <106 ng/ml or <53 ng/ml, for HCQ doses of 400 or 200 mg/d, respectively. Associations with the risk of a flare (defined as a SLEDAI-2K increase ≥4 points, initiation of prednisone or immunosuppressive drugs, or new renal involvement) were studied with logistic regression, and associations with damage (first SLICC/ACR Damage Index (SDI) increase ≥1 point) and mortality with separate Cox proportional hazard models.

Results. Of 1849 cohort subjects, 660 patients (88% women) were included. Median (interquartile range) serum HCQ was 388 ng/ml (244–566); 48 patients (7.3%) had severe HCQ non-adherence. No covariates were clearly associated with severe non-adherence, which was however independently associated with both flare (OR 3.38; 95% CI 1.80–6.42) and an increase in the SDI within each of the first 3 years (HR 1.92 at 3 years; 95% CI 1.05–3.50). Eleven patients died within 5 years, including 3 with severe non-adherence (crude HR 5.41; 95% CI 1.43–20.39).

Conclusion. Severe non-adherence was independently associated with the risks of an SLE flare in the following year, early damage, and 5-year mortality.

Original language	English
Journal	Arthritis and Rheumatology
Early online date	17 Jul 2023
DOIs	https://doi.org/10.1002/art.42645
Publication status	E-pub ahead of print - 17 Jul 2023

Keywords

Systemic lupus erythematosus
hydroxychloroquine
adherence
flare
damage

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10.1002/art.42645Licence: Creative Commons: Attribution (CC BY)

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Nguyen, Y., Blanchet, B., Urowitz, M. B., Hanly, J. G., Gordon, C., Bae, S.-C., Romero-Diaz, J., Sanchez-Guerro, J., Clarke, A. E., Bernatsky, S., Wallace, D. J., Isenberg, D., Rahman, A., Merrill, J. T., Fortin, P., Gladman, D., Bruce, I. N., Petri, M., Ginzler, E., ... Costedoat-Chalumeau, N. (2023). Association between severe non-adherence to hydroxychloroquine and SLE flares, damage, and mortality in 660 patients from the SLICC Inception Cohort. Arthritis and Rheumatology. Advance online publication. https://doi.org/10.1002/art.42645

@article{3e79437b59d24958962e13cb928a4227,

title = "Association between severe non-adherence to hydroxychloroquine and SLE flares, damage, and mortality in 660 patients from the SLICC Inception Cohort",

abstract = "Objectives. To assess the associations of severe non-adherence to HCQ, objectively assessed by HCQ serum levels, and risks of SLE flares, damage, and mortality over 5 years of follow-up.Methods. The SLICC Inception Cohort is an international multicenter initiative (33 centers; 11 countries). Serum of patients prescribed HCQ for at least 3 months at enrollment were analyzed. Severe non-adherence was defined by a serum HCQ level <106 ng/ml or <53 ng/ml, for HCQ doses of 400 or 200 mg/d, respectively. Associations with the risk of a flare (defined as a SLEDAI-2K increase ≥4 points, initiation of prednisone or immunosuppressive drugs, or new renal involvement) were studied with logistic regression, and associations with damage (first SLICC/ACR Damage Index (SDI) increase ≥1 point) and mortality with separate Cox proportional hazard models. Results. Of 1849 cohort subjects, 660 patients (88% women) were included. Median (interquartile range) serum HCQ was 388 ng/ml (244–566); 48 patients (7.3%) had severe HCQ non-adherence. No covariates were clearly associated with severe non-adherence, which was however independently associated with both flare (OR 3.38; 95% CI 1.80–6.42) and an increase in the SDI within each of the first 3 years (HR 1.92 at 3 years; 95% CI 1.05–3.50). Eleven patients died within 5 years, including 3 with severe non-adherence (crude HR 5.41; 95% CI 1.43–20.39).Conclusion. Severe non-adherence was independently associated with the risks of an SLE flare in the following year, early damage, and 5-year mortality. ",

keywords = "Systemic lupus erythematosus, hydroxychloroquine, adherence, flare, damage",

author = "Yann Nguyen and Beno{\^i}t Blanchet and Urowitz, {Murray B} and Hanly, {John G} and Caroline Gordon and Sang-Cheol Bae and Juanita Romero-Diaz and Jorge Sanchez-Guerro and Clarke, {Ann E} and Sasha Bernatsky and Wallace, {Daniel J} and David Isenberg and Anisur Rahman and Merrill, {Joan T} and Paul Fortin and Dafna Gladman and Bruce, {Ian N} and Michelle Petri and Ellen Ginzler and Dooley, {Mary Anne} and Rosalind Ramsey-Goldman and Susan Manzi and Andreas Jonsen and Graciela Alarcon and {van Vollenhoven}, Ronald and Cynthia Aranow and {Le Guern}, V{\'e}ronique and Meggan Mackay and Guillermo Ruiz-Irastorza and Sam Lim and Murat Inanc and KC Kalunian and Soren Jacobsen and Peschken, {Christine A} and Kamen, {Diane L} and Anca Askanase and Jill Buyon and Nathalie Costedoat-Chalumeau",

year = "2023",

month = jul,

day = "17",

doi = "10.1002/art.42645",

language = "English",

journal = "Arthritis and Rheumatology",

issn = "2326-5191",

publisher = "Wiley",

}

Nguyen, Y, Blanchet, B, Urowitz, MB, Hanly, JG, Gordon, C, Bae, S-C, Romero-Diaz, J, Sanchez-Guerro, J, Clarke, AE, Bernatsky, S, Wallace, DJ, Isenberg, D, Rahman, A, Merrill, JT, Fortin, P, Gladman, D, Bruce, IN, Petri, M, Ginzler, E, Dooley, MA, Ramsey-Goldman, R, Manzi, S, Jonsen, A, Alarcon, G, van Vollenhoven, R, Aranow, C, Le Guern, V, Mackay, M, Ruiz-Irastorza, G, Lim, S, Inanc, M, Kalunian, KC, Jacobsen, S, Peschken, CA, Kamen, DL, Askanase, A, Buyon, J & Costedoat-Chalumeau, N 2023, 'Association between severe non-adherence to hydroxychloroquine and SLE flares, damage, and mortality in 660 patients from the SLICC Inception Cohort', Arthritis and Rheumatology. https://doi.org/10.1002/art.42645

TY - JOUR

T1 - Association between severe non-adherence to hydroxychloroquine and SLE flares, damage, and mortality in 660 patients from the SLICC Inception Cohort

AU - Nguyen, Yann

AU - Blanchet, Benoît

AU - Urowitz, Murray B

AU - Hanly, John G

AU - Gordon, Caroline

AU - Bae, Sang-Cheol

AU - Romero-Diaz, Juanita

AU - Sanchez-Guerro, Jorge

AU - Clarke, Ann E

AU - Bernatsky, Sasha

AU - Wallace, Daniel J

AU - Isenberg, David

AU - Rahman, Anisur

AU - Merrill, Joan T

AU - Fortin, Paul

AU - Gladman, Dafna

AU - Bruce, Ian N

AU - Petri, Michelle

AU - Ginzler, Ellen

AU - Dooley, Mary Anne

AU - Ramsey-Goldman, Rosalind

AU - Manzi, Susan

AU - Jonsen, Andreas

AU - Alarcon, Graciela

AU - van Vollenhoven, Ronald

AU - Aranow, Cynthia

AU - Le Guern, Véronique

AU - Mackay, Meggan

AU - Ruiz-Irastorza, Guillermo

AU - Lim, Sam

AU - Inanc, Murat

AU - Kalunian, KC

AU - Jacobsen, Soren

AU - Peschken, Christine A

AU - Kamen, Diane L

AU - Askanase, Anca

AU - Buyon, Jill

AU - Costedoat-Chalumeau, Nathalie

PY - 2023/7/17

Y1 - 2023/7/17

N2 - Objectives. To assess the associations of severe non-adherence to HCQ, objectively assessed by HCQ serum levels, and risks of SLE flares, damage, and mortality over 5 years of follow-up.Methods. The SLICC Inception Cohort is an international multicenter initiative (33 centers; 11 countries). Serum of patients prescribed HCQ for at least 3 months at enrollment were analyzed. Severe non-adherence was defined by a serum HCQ level <106 ng/ml or <53 ng/ml, for HCQ doses of 400 or 200 mg/d, respectively. Associations with the risk of a flare (defined as a SLEDAI-2K increase ≥4 points, initiation of prednisone or immunosuppressive drugs, or new renal involvement) were studied with logistic regression, and associations with damage (first SLICC/ACR Damage Index (SDI) increase ≥1 point) and mortality with separate Cox proportional hazard models. Results. Of 1849 cohort subjects, 660 patients (88% women) were included. Median (interquartile range) serum HCQ was 388 ng/ml (244–566); 48 patients (7.3%) had severe HCQ non-adherence. No covariates were clearly associated with severe non-adherence, which was however independently associated with both flare (OR 3.38; 95% CI 1.80–6.42) and an increase in the SDI within each of the first 3 years (HR 1.92 at 3 years; 95% CI 1.05–3.50). Eleven patients died within 5 years, including 3 with severe non-adherence (crude HR 5.41; 95% CI 1.43–20.39).Conclusion. Severe non-adherence was independently associated with the risks of an SLE flare in the following year, early damage, and 5-year mortality.

AB - Objectives. To assess the associations of severe non-adherence to HCQ, objectively assessed by HCQ serum levels, and risks of SLE flares, damage, and mortality over 5 years of follow-up.Methods. The SLICC Inception Cohort is an international multicenter initiative (33 centers; 11 countries). Serum of patients prescribed HCQ for at least 3 months at enrollment were analyzed. Severe non-adherence was defined by a serum HCQ level <106 ng/ml or <53 ng/ml, for HCQ doses of 400 or 200 mg/d, respectively. Associations with the risk of a flare (defined as a SLEDAI-2K increase ≥4 points, initiation of prednisone or immunosuppressive drugs, or new renal involvement) were studied with logistic regression, and associations with damage (first SLICC/ACR Damage Index (SDI) increase ≥1 point) and mortality with separate Cox proportional hazard models. Results. Of 1849 cohort subjects, 660 patients (88% women) were included. Median (interquartile range) serum HCQ was 388 ng/ml (244–566); 48 patients (7.3%) had severe HCQ non-adherence. No covariates were clearly associated with severe non-adherence, which was however independently associated with both flare (OR 3.38; 95% CI 1.80–6.42) and an increase in the SDI within each of the first 3 years (HR 1.92 at 3 years; 95% CI 1.05–3.50). Eleven patients died within 5 years, including 3 with severe non-adherence (crude HR 5.41; 95% CI 1.43–20.39).Conclusion. Severe non-adherence was independently associated with the risks of an SLE flare in the following year, early damage, and 5-year mortality.

KW - Systemic lupus erythematosus

KW - hydroxychloroquine

KW - adherence

KW - flare

KW - damage

U2 - 10.1002/art.42645

DO - 10.1002/art.42645

M3 - Article

SN - 2326-5191

JO - Arthritis and Rheumatology

JF - Arthritis and Rheumatology

ER -

Association between severe non-adherence to hydroxychloroquine and SLE flares, damage, and mortality in 660 patients from the SLICC Inception Cohort

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Keywords

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