OP0333 RISK FACTORS OF ANTIMALARIAL-INDUCED RETINOPATHY IN SYSTEMIC LUPUS ERYTHEMATOSUS AND OTHER AUTOIMMUNE CONDITIONS
Authors: H. Y. Liu, G. Cramarossa, J. Pope
Journal: Annals of the Rheumatic Diseases (2020)

Background: Hydroxychloroquine (HCQ) and chloroquine (CQ) are effective antimalarial (AM) medications for systemic lupus erythematosus (SLE) and other autoimmune conditions such as rheumatoid arthritis (RA). AM-induced retinopathy is a well-recognized irreversible complication with variable incidences [1]. Few studies have compared the AM-induced retinopathy between rheumatologic conditions. Objectives: To describe the pattern of AM-associated retinopathy, including diagnosis of SLE as a risk factor. Methods: A chart review was conducted at an urban Canadian center. Each patient was classified as SLE, based on ACR criteria, or non-SLE. Minimum duration of AM use was 3 months. AM-induced retinopathy was classified as possible or definite, and was determined based on characteristic visual field loss, abnormal retinal imaging, and eye specialists’ opinion. Univariate and multivariate logistic regressions were performed to determine factors associated with definite AM-induced retinopathy. Sensitivity analyses included inclusion of possible AM-induced retinopathy and stratification of analysis by diagnosis and by CQ versus HCQ. Results: Of the 680 patients, 282 patients had SLE and the remaining had RA (N=224), cutaneous lupus (N=41), or other connective tissue diseases (N=131). Patients with SLE tended to be younger, female, and had relatively more CQ and total AM exposure (Table 1). Definite AM-induced retinopathy was observed in 12 patients, 11 of whom had SLE and 7 had chloroquine exposure (Figure 1). The earliest toxicity occured after 5.4 years of AM use, and prevalence beyond 5 years was 2.7%. Table 1. Patient characteristics. Data represented as N (%) or means (SD) SLE (N=282) Non-SLE (N=398)* Total (N=680) P Age 40.1 ± 15 51 ± 13.8 46.5 ± 15.3 5.72×10 -21 Female 258 (91%) 333 (84%) 591 (87%) 4.19×10 -3 AM duration (years) 11.5 ± 8.1 7.3 ± 6.2 9.1 ± 7.3 3.52×10 -11 CQ ever 35 (12%) 21 (5%) 56 (8%) 1.41×10 -3 *other connective tissue diseases and RA In univariate logistic regression (Table 2), a diagnosis of SLE (P=7.95×10 -3 ; OR= 16.1; 95% confidence interval (CI)= [2.1, 125]), and cumulative CQ dose (P=1.13×10 -2 ; OR= 1.002; 95% CI=[1.000, 1.003]) were significantly associated with definite AM-induced retinopathy. When possible retinopathy was included in the analysis, both SLE (P=7.27×10 -3 ; OR=3.12, 95% CI=[1.39, 7.00]) and CQ cumulative dose (P= 6.16×10 -7 ; OR= 1.002; 95% CI=[1.001, 1.003]) remained significant. Total AM duration and hypertension also had significant associations. In multivariate analysis, diagnosis of SLE was significantly associated with ocular toxicity (P=1.49×10 -2 ; OR=14.2; 95%CI: [1.83-127]) after adjusting for CQ/HCQ dosages, age, sex, weight, hypertension and renal impairment. Table 2. Univariate logistic regression for risk of AM-induced retinopathy. Data represented as N (%) or mean ± SD Definite retinopathy Possible or definite retinopathy No retinopathy N=668 Retinopathy N=12 P No retinopathy N=652 Retinopathy N=28 P Age 46.5 ± 15.3 43.2 ± 14.3 0.452 46.4 ± 15.4 47.1 ± 12.4 0.832 Female 580 (87%) 11 (92%) 0.626 567 (87%) 24 (86%) 0.848 Weight (kg) 76.5 ± 19.5 67.3 ± 12.8 0.098 76.5 ± 19.5 73.5 ± 17.8 0.424 SLE Diagnosis 271 (41%) 11 (92%) 0.008 263 (40%) 19 (68%) 0.006 AM duration (years) 9 ± 7.4 11.7 ± 5.8 0.215 8.9 ± 7.3 12.8 ± 6.8 0.007 AM&gt; 5 years 417 (63%) 0 - 250 (40%) 1 (3%) 0.006 HCQ dose (mg/kg/day) 5.2 ± 15.5 5.9 ± 1.5 0.891 5.2 ± 15.6 5.3 ± 1.4 0.971 HCQ total dose (g) 1042 ± 913.8 1235 ± 1032 0.471 1340 ± 914 1187 ± 955 0.404 CQ total dose (g) 46 ± 205.1 225± 291 0.011 37.6 ± 174) 318 ± 529 6.16×10 -7 Renal Impairment 100 (15%) 2 (17%) 0.883 99 (15%) 3 (11%) 0.506 Hypertension 298 (45%) 5 (42%) 0.832 285 (44%) 18 (64%) 0.038 Diabetes 61 (9%) 1 (8%) 0.924 59 (9%) 3 (11%) 0.765 Conclusion: The risk of AM-induced retinal toxicity increases after 5 years of use. SLE patients may be at increased risk due to longer treatment duration, AM choice, and underlying disease processes. References: [1]Petri M, Elkhalifa M, Li J. 15 Frequency of hydroxychloroquine retinopathy in the hopkins lupus cohort. Lupus Science &amp; Medicine 2019;6:doi: 10.1136/lupus-2019-lsm.15 Disclosure of Interests: Hsin Yen Liu: None declared, Gemma Cramarossa: None declared, Janet Pope Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly &amp; Company, Merck, Roche, Seattle Genetics, UCB, Consultant of: AbbVie, Actelion, Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eicos Sciences, Eli Lilly &amp; Company, Emerald, Gilead Sciences, Inc., Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB, Speakers bureau: UCB