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

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

doi:10.1136/lupus-2022-000789

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

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

^*Corresponding author for this work

Inflammation and Ageing

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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	e000789
Number of pages	6
Journal	Lupus Science and Medicine
Volume	9
DOIs	https://doi.org/10.1136/lupus-2022-000789
Publication status	Published - 17 Nov 2022

Keywords

Epidemiology
lupus erythematosus
systemic
outcome assessment
health care

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10.1136/lupus-2022-000789Licence: Creative Commons: Attribution (CC BY)

Almeida-Brasil2022RetinalFinal published version, 750 KBLicence: Creative Commons: Attribution (CC BY)

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Almeida-Brasil, C., Hanly, J. G., Urowitz, M., Clarke, A. E., Ruiz-Irastorza, G., Gordon, C., Ramsey-Goldman, R., Petri, M. A., Ginzler, E., Wallace, D. J., Bae, S.-C., Romero-Diaz, J., Dooley, M. A., Peschken, C. A., Isenberg, D., Rahman, A., Manzi, S., Jacobsen, S., Lim, S. S., ... Bernatsky, S. (2022). Retinal toxicity in a multinational inception cohort of systemic lupus patients on hydroxychloroquine. Lupus Science and Medicine, 9, Article e000789. https://doi.org/10.1136/lupus-2022-000789

@article{aaa03c0bdd4c4c39b1308c324c21832e,

title = "Retinal toxicity in a multinational inception cohort of systemic lupus patients 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, lupus erythematosus, systemic, outcome assessment, health care",

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

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",

}

Almeida-Brasil, C, Hanly, JG, Urowitz, M, Clarke, AE, Ruiz-Irastorza, G, Gordon, C, Ramsey-Goldman, R, Petri, MA, Ginzler, E, Wallace, DJ, Bae, S-C, Romero-Diaz, J, Dooley, MA, Peschken, CA, Isenberg, D, Rahman, A, Manzi, S, Jacobsen, S, Lim, SS, van Vollenhoven, R, Nived, O, Jonsen, A, Kamen, DL, Aranow, C, Sanchez-Guerrero, J, Gladman, D, Fortin, P, Alarcon, G, Merrill, JT, Kalunian, KC, Ramos-Casals, M, Steinsson, K, Zoma, A, Askanase, A, Khamashta, MA, Bruce, IN, Inanc, M, Lukusa, L & Bernatsky, S 2022, 'Retinal toxicity in a multinational inception cohort of systemic lupus patients on hydroxychloroquine', Lupus Science and Medicine, vol. 9, e000789. https://doi.org/10.1136/lupus-2022-000789

TY - JOUR

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

AU - Almeida-Brasil, Celline

AU - Hanly, John G

AU - Urowitz, Murray

AU - Clarke, Ann E

AU - Ruiz-Irastorza, G

AU - Gordon, Caroline

AU - Ramsey-Goldman, Rosalind

AU - Petri, Michelle A

AU - Ginzler, Ellen

AU - Wallace, Daniel J

AU - Bae, Sang-Cheol

AU - Romero-Diaz, Juanita

AU - Dooley, Mary Anne

AU - Peschken, Christine A

AU - Isenberg, David

AU - Rahman, Anisur

AU - Manzi, Susan

AU - Jacobsen, Soren

AU - Lim, S. Sam

AU - van Vollenhoven, Ronald

AU - Nived, Ola

AU - Jonsen, Andreas

AU - Kamen, Diane L

AU - Aranow, Cynthia

AU - Sanchez-Guerrero, Jorge

AU - Gladman, Dafna

AU - Fortin, Paul

AU - Alarcon, Graciela

AU - Merrill, Joan T

AU - Kalunian, Kenneth C

AU - Ramos-Casals, Manuel

AU - Steinsson, Kristjan

AU - Zoma, Asad

AU - Askanase, Anca

AU - Khamashta, Munther A

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 - lupus erythematosus

KW - systemic

KW - outcome assessment

KW - health care

U2 - 10.1136/lupus-2022-000789

DO - 10.1136/lupus-2022-000789

M3 - Article

SN - 2053-8790

VL - 9

JO - Lupus Science and Medicine

JF - Lupus Science and Medicine

M1 - e000789

ER -

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

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Keywords

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