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; Søren 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, Søren Jacobsen, S Sam Lim, Ronald van VollenhovenOla 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

Afdeling for Rygkirurgi, Led- og Bindevævssygdomme

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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.

Originalsprog	Engelsk
Artikelnummer	000789
Tidsskrift	Lupus science & medicine
Vol/bind	9
Udgave nummer	1
ISSN	2053-8790
DOI	https://doi.org/10.1136/lupus-2022-000789
Status	Udgivet - nov. 2022

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10.1136/lupus-2022-000789

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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., Lim, S. S., ... Bernatsky, S. (2022). Retinal toxicity in a multinational inception cohort of patients with systemic lupus on hydroxychloroquine. Lupus science & medicine, 9(1), Artikel 000789. https://doi.org/10.1136/lupus-2022-000789

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, S, Lim, SS, 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 & medicine, bind 9, nr. 1, 000789. https://doi.org/10.1136/lupus-2022-000789

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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 = "Humans, Female, Aged, Male, Hydroxychloroquine/adverse effects, Antirheumatic Agents/adverse effects, Lupus Erythematosus, Systemic/complications, Retinal Diseases/chemically induced, Chloroquine",

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 S{\o}ren Jacobsen and Lim, {S Sam} 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 = "{\textcopyright} Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.",

year = "2022",

month = nov,

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

language = "English",

volume = "9",

journal = "Lupus science & medicine",

issn = "2053-8790",

publisher = "BMJ Publishing Group",

number = "1",

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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, Søren

AU - Lim, S Sam

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

Y1 - 2022/11

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 - Humans

KW - Female

KW - Aged

KW - Male

KW - Hydroxychloroquine/adverse effects

KW - Antirheumatic Agents/adverse effects

KW - Lupus Erythematosus, Systemic/complications

KW - Retinal Diseases/chemically induced

KW - Chloroquine

UR - http://www.scopus.com/inward/record.url?scp=85143398652&partnerID=8YFLogxK

U2 - 10.1136/lupus-2022-000789

DO - 10.1136/lupus-2022-000789

M3 - Journal article

C2 - 36396267

SN - 2053-8790

VL - 9

JO - Lupus science & medicine

JF - Lupus science & medicine

IS - 1

M1 - 000789

ER -

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

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