Retinal toxicity in a multinational inception cohort of patients with systemic lupus on hydroxychloroquine

Celline C. Almeida-Brasil; John G. Hanly; Murray Urowitz; Ann Elaine Clarke; Guillermo Ruiz-Irastorza; Caroline Gordon; Rosalind Ramsey-Goldman; Michelle A. Petri; Ellen M. Ginzler; Daniel J. Wallace; Sang-Cheol Bae; Juanita Romero-Diaz; Mary-Anne Dooley; Christine Peschken; David Isenberg; Anisur Rahman; Susan Manzi; S. ren Jacobsen; S. Sam Lim; Ronald van Vollenhoven; Ola Nived; Andreas Jönsen; Diane L. Kamen; Cynthia Aranow; Jorge Sánchez-Guerrero; Dafna D. Gladman; Paul R. Fortin; Graciela S. Alarcon; Joan T. Merrill; Kenneth Kalunian; Manuel Ramos-Casals; Kristjan Steinsson; A. Zoma; Anca D. Askanase; Munther Khamashta; Ian N. Bruce; Murat Inanc; Luck Lukusa; Sasha Bernatsky

doi:10.1136/lupus-2022-000789

Retinal toxicity in a multinational inception cohort of patients with systemic lupus on hydroxychloroquine

Celline C. Almeida-Brasil
, John G. Hanly
, Murray Urowitz
, Ann Elaine Clarke
, Guillermo Ruiz-Irastorza
, Caroline Gordon
, Rosalind Ramsey-Goldman
, Michelle A. Petri
, Ellen M. Ginzler
, Daniel J. Wallace
, Sang-Cheol Bae
, Juanita Romero-Diaz
, Mary-Anne Dooley
, Christine Peschken
, David Isenberg
, Anisur Rahman
, Susan Manzi
, S. ren Jacobsen
, S. Sam Lim
, Ronald van Vollenhoven

Ola Nived, Andreas Jönsen, Diane L. Kamen, Cynthia Aranow, Jorge Sánchez-Guerrero, Dafna D. Gladman, Paul R. Fortin, Graciela S. Alarcon, Joan T. Merrill, Kenneth Kalunian, Manuel Ramos-Casals, Kristjan Steinsson, A. Zoma, Anca D. Askanase, Munther Khamashta, Ian N. Bruce, Murat Inanc, Luck Lukusa, Sasha Bernatsky^*

^*Corresponding author for this work

McGill University
Dalhousie University
University of Toronto
University of Calgary
Biocruces Bizkaia
University of Birmingham
Northwestern University
Johns Hopkins University
SUNY Downstate Health Sciences University
Cedars-Sinai Medical Center
Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
University of North Carolina at Chapel Hill
University of Manitoba
University College London
West Penn Allegheny Health System
University of Copenhagen
Emory University
Amsterdam Rheumatology and Immunology Center
Lund University
Medical University of South Carolina
Northwell Health System
Division of Neuroradiology, Joint Department of Medical Imaging and Neurosurgery, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada
Université Laval
University of Alabama at Birmingham
Oklahoma Medical Research Foundation
University of California at San Diego
University of Barcelona
Landspitali University Hospital
NHS Lanarkshire
Columbia University
Paediatric Allergy Group, Department of Women and Children's Health, King's College London, St. Thomas' Hospital, London, UK
University of Manchester
Istanbul University
Johns Hopkins University School of Medicine
Hanyang University
Great Ormond St Hospital for Children NHS Trust
Toronto Western Hospital, Tanz Centre for Research in Neurodegenerative Disease, Toronto, ON, Canada
Columbia University Medical Center
King's College London
McGill University Health Center

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Abstract

Objective To evaluate hydroxychloroquine (HCQ)-related retinal toxicity in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort. Methods Data were collected at annual study visits between 1999 and 2019. We followed patients with incident SLE from first visit on HCQ (time zero) up to time of retinal toxicity (outcome), death, loss-to-follow-up or end of study. Potential retinal toxicity was identified from SLICC Damage Index scores; cases were confirmed with chart review. Using cumulative HCQ duration as the time axis, we constructed univariate Cox regression models to assess if covariates (ie, HCQ daily dose/kg, sex, race/ethnicity, age at SLE onset, education, body mass index, renal damage, chloroquine use) were associated with HCQ-related retinal toxicity. Results We studied 1460 patients (89% female, 52% white). Retinal toxicity was confirmed in 11 patients (incidence 1.0 per 1000 person-years, 0.8% overall). Average cumulative time on HCQ in those with retinal toxicity was 7.4 (SD 3.2) years; the first case was detected 4 years after HCQ initiation. Risk of retinal toxicity was numerically higher in older patients at SLE diagnosis (univariate HR 1.05, 95% CI 1.01 to 1.09). Conclusions This is the first assessment of HCQ and retinal disease in incident SLE. We did not see any cases of retinopathy within the first 4 years of HCQ. Cumulative HCQ may be associated with increased risk. Ophthalmology monitoring (and formal assessment of cases of potential toxicity, by a retinal specialist) remains important, especially in patients on HCQ for 10+ years, those needing higher doses and those of older age at SLE diagnosis.

Original language	English
Article number	000789
Journal	Lupus Science and Medicine
Volume	9
Issue number	1
DOIs	https://doi.org/10.1136/lupus-2022-000789
Publication status	Published - 17 Nov 2022

Keywords

epidemiology
health care
lupus erythematosus
outcome assessment
systemic

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Almeida-Brasil, C. C., Hanly, J. G., Urowitz, M., Clarke, A. E., Ruiz-Irastorza, G., Gordon, C., Ramsey-Goldman, R., Petri, M. A., Ginzler, E. M., Wallace, D. J., Bae, S.-C., Romero-Diaz, J., Dooley, M.-A., Peschken, C., Isenberg, D., Rahman, A., Manzi, S., Jacobsen, S. R., Sam Lim, S., ... Bernatsky, S. (2022). Retinal toxicity in a multinational inception cohort of patients with systemic lupus on hydroxychloroquine. Lupus Science and Medicine, 9(1), Article 000789. https://doi.org/10.1136/lupus-2022-000789

@article{bbad524485f34b029df39bf091dce8b3,

title = "Retinal toxicity in a multinational inception cohort of patients with systemic lupus on hydroxychloroquine",

abstract = "Objective To evaluate hydroxychloroquine (HCQ)-related retinal toxicity in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort. Methods Data were collected at annual study visits between 1999 and 2019. We followed patients with incident SLE from first visit on HCQ (time zero) up to time of retinal toxicity (outcome), death, loss-to-follow-up or end of study. Potential retinal toxicity was identified from SLICC Damage Index scores; cases were confirmed with chart review. Using cumulative HCQ duration as the time axis, we constructed univariate Cox regression models to assess if covariates (ie, HCQ daily dose/kg, sex, race/ethnicity, age at SLE onset, education, body mass index, renal damage, chloroquine use) were associated with HCQ-related retinal toxicity. Results We studied 1460 patients (89\% female, 52\% white). Retinal toxicity was confirmed in 11 patients (incidence 1.0 per 1000 person-years, 0.8\% overall). Average cumulative time on HCQ in those with retinal toxicity was 7.4 (SD 3.2) years; the first case was detected 4 years after HCQ initiation. Risk of retinal toxicity was numerically higher in older patients at SLE diagnosis (univariate HR 1.05, 95\% CI 1.01 to 1.09). Conclusions This is the first assessment of HCQ and retinal disease in incident SLE. We did not see any cases of retinopathy within the first 4 years of HCQ. Cumulative HCQ may be associated with increased risk. Ophthalmology monitoring (and formal assessment of cases of potential toxicity, by a retinal specialist) remains important, especially in patients on HCQ for 10+ years, those needing higher doses and those of older age at SLE diagnosis.",

keywords = "epidemiology, health care, lupus erythematosus, outcome assessment, systemic",

author = "Almeida-Brasil, \{Celline C.\} and Hanly, \{John G.\} and Murray Urowitz and Clarke, \{Ann Elaine\} and Guillermo Ruiz-Irastorza and Caroline Gordon and Rosalind Ramsey-Goldman and Petri, \{Michelle A.\} and Ginzler, \{Ellen M.\} and Wallace, \{Daniel J.\} and Sang-Cheol Bae and Juanita Romero-Diaz and Mary-Anne Dooley and Christine Peschken and David Isenberg and Anisur Rahman and Susan Manzi and Jacobsen, \{S. ren\} and \{Sam Lim\}, S. and \{van Vollenhoven\}, Ronald and Ola Nived and Andreas J{\"o}nsen and Kamen, \{Diane L.\} and Cynthia Aranow and Jorge S{\'a}nchez-Guerrero and Gladman, \{Dafna D.\} and Fortin, \{Paul R.\} and Alarcon, \{Graciela S.\} and Merrill, \{Joan T.\} and Kenneth Kalunian and Manuel Ramos-Casals and Kristjan Steinsson and A. Zoma and Askanase, \{Anca D.\} and Munther Khamashta and Bruce, \{Ian N.\} and Murat Inanc and Luck Lukusa and Sasha Bernatsky",

note = "Publisher Copyright: {\textcopyright} Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.",

year = "2022",

month = nov,

day = "17",

doi = "10.1136/lupus-2022-000789",

language = "English",

volume = "9",

journal = "Lupus Science and Medicine",

issn = "2053-8790",

publisher = "BMJ Publishing Group",

number = "1",

}

Almeida-Brasil, CC, Hanly, JG, Urowitz, M, Clarke, AE, Ruiz-Irastorza, G, Gordon, C, Ramsey-Goldman, R, Petri, MA, Ginzler, EM, Wallace, DJ, Bae, S-C, Romero-Diaz, J, Dooley, M-A, Peschken, C, Isenberg, D, Rahman, A, Manzi, S, Jacobsen, SR, Sam Lim, S, van Vollenhoven, R, Nived, O, Jönsen, A, Kamen, DL, Aranow, C, Sánchez-Guerrero, J, Gladman, DD, Fortin, PR, Alarcon, GS, Merrill, JT, Kalunian, K, Ramos-Casals, M, Steinsson, K, Zoma, A, Askanase, AD, Khamashta, M, Bruce, IN, Inanc, M, Lukusa, L & Bernatsky, S 2022, 'Retinal toxicity in a multinational inception cohort of patients with systemic lupus on hydroxychloroquine', Lupus Science and Medicine, vol. 9, no. 1, 000789. https://doi.org/10.1136/lupus-2022-000789

TY - JOUR

T1 - Retinal toxicity in a multinational inception cohort of patients with systemic lupus on hydroxychloroquine

AU - Almeida-Brasil, Celline C.

AU - Hanly, John G.

AU - Urowitz, Murray

AU - Clarke, Ann Elaine

AU - Ruiz-Irastorza, Guillermo

AU - Gordon, Caroline

AU - Ramsey-Goldman, Rosalind

AU - Petri, Michelle A.

AU - Ginzler, Ellen M.

AU - Wallace, Daniel J.

AU - Bae, Sang-Cheol

AU - Romero-Diaz, Juanita

AU - Dooley, Mary-Anne

AU - Peschken, Christine

AU - Isenberg, David

AU - Rahman, Anisur

AU - Manzi, Susan

AU - Jacobsen, S. ren

AU - Sam Lim, S.

AU - van Vollenhoven, Ronald

AU - Nived, Ola

AU - Jönsen, Andreas

AU - Kamen, Diane L.

AU - Aranow, Cynthia

AU - Sánchez-Guerrero, Jorge

AU - Gladman, Dafna D.

AU - Fortin, Paul R.

AU - Alarcon, Graciela S.

AU - Merrill, Joan T.

AU - Kalunian, Kenneth

AU - Ramos-Casals, Manuel

AU - Steinsson, Kristjan

AU - Zoma, A.

AU - Askanase, Anca D.

AU - Khamashta, Munther

AU - Bruce, Ian N.

AU - Inanc, Murat

AU - Lukusa, Luck

AU - Bernatsky, Sasha

PY - 2022/11/17

Y1 - 2022/11/17

N2 - Objective To evaluate hydroxychloroquine (HCQ)-related retinal toxicity in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort. Methods Data were collected at annual study visits between 1999 and 2019. We followed patients with incident SLE from first visit on HCQ (time zero) up to time of retinal toxicity (outcome), death, loss-to-follow-up or end of study. Potential retinal toxicity was identified from SLICC Damage Index scores; cases were confirmed with chart review. Using cumulative HCQ duration as the time axis, we constructed univariate Cox regression models to assess if covariates (ie, HCQ daily dose/kg, sex, race/ethnicity, age at SLE onset, education, body mass index, renal damage, chloroquine use) were associated with HCQ-related retinal toxicity. Results We studied 1460 patients (89% female, 52% white). Retinal toxicity was confirmed in 11 patients (incidence 1.0 per 1000 person-years, 0.8% overall). Average cumulative time on HCQ in those with retinal toxicity was 7.4 (SD 3.2) years; the first case was detected 4 years after HCQ initiation. Risk of retinal toxicity was numerically higher in older patients at SLE diagnosis (univariate HR 1.05, 95% CI 1.01 to 1.09). Conclusions This is the first assessment of HCQ and retinal disease in incident SLE. We did not see any cases of retinopathy within the first 4 years of HCQ. Cumulative HCQ may be associated with increased risk. Ophthalmology monitoring (and formal assessment of cases of potential toxicity, by a retinal specialist) remains important, especially in patients on HCQ for 10+ years, those needing higher doses and those of older age at SLE diagnosis.

AB - Objective To evaluate hydroxychloroquine (HCQ)-related retinal toxicity in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort. Methods Data were collected at annual study visits between 1999 and 2019. We followed patients with incident SLE from first visit on HCQ (time zero) up to time of retinal toxicity (outcome), death, loss-to-follow-up or end of study. Potential retinal toxicity was identified from SLICC Damage Index scores; cases were confirmed with chart review. Using cumulative HCQ duration as the time axis, we constructed univariate Cox regression models to assess if covariates (ie, HCQ daily dose/kg, sex, race/ethnicity, age at SLE onset, education, body mass index, renal damage, chloroquine use) were associated with HCQ-related retinal toxicity. Results We studied 1460 patients (89% female, 52% white). Retinal toxicity was confirmed in 11 patients (incidence 1.0 per 1000 person-years, 0.8% overall). Average cumulative time on HCQ in those with retinal toxicity was 7.4 (SD 3.2) years; the first case was detected 4 years after HCQ initiation. Risk of retinal toxicity was numerically higher in older patients at SLE diagnosis (univariate HR 1.05, 95% CI 1.01 to 1.09). Conclusions This is the first assessment of HCQ and retinal disease in incident SLE. We did not see any cases of retinopathy within the first 4 years of HCQ. Cumulative HCQ may be associated with increased risk. Ophthalmology monitoring (and formal assessment of cases of potential toxicity, by a retinal specialist) remains important, especially in patients on HCQ for 10+ years, those needing higher doses and those of older age at SLE diagnosis.

KW - epidemiology

KW - health care

KW - lupus erythematosus

KW - outcome assessment

KW - systemic

UR - https://www.scopus.com/pages/publications/85143398652

U2 - 10.1136/lupus-2022-000789

DO - 10.1136/lupus-2022-000789

M3 - Article

C2 - 36396267

SN - 2053-8790

VL - 9

JO - Lupus Science and Medicine

JF - Lupus Science and Medicine

IS - 1

M1 - 000789

ER -

Retinal toxicity in a multinational inception cohort of patients with systemic lupus on hydroxychloroquine

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