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Kidney disease and hydroxychloroquine dose are risk factors for developing retinopathy

Presented by
Dr April Jorge, Massachusetts General Hospital, MA, USA
ACR 2021
Long-term use and high-dose treatment were among the independent risk factors that distinctly augment the risk of retinopathy for patients with systemic lupus or other rheumatoid diseases treated with hydroxychloroquine. Another risk factor is comorbid chronic kidney disease, which nearly doubled the retinopathy risk.

Previous findings suggested a 5 times higher risk for retinopathy in patients within the first 10 years of hydroxychloroquine treatment when treated with 5 mg/kg/day; thus, guidelines recommend to not pass this threshold [1,2]. To identify risk factors for hydroxychloroquine retinopathy, Dr April Jorge (Massachusetts General Hospital, MA, USA) and colleagues obtained data from the Kaiser Permanente Northern California consortium to ascertain a large cohort of 4,899 subjects with systemic lupus erythematosus or other rheumatoid diseases with incident hydroxychloroquine use of ≥5 years between 1997 and 2020 [3].

All participants had at least 1 Spectral-Domain Optical Coherence Tomography (SD-OCT) scan after 5 years of treatment. Each SD-OCT was reviewed by an expert ophthalmologist who graded existing hydroxychloroquine retinopathy into mild, moderate, or severe. A second expert evaluation was done for all pathologies and a sample of normal findings. Cases were matched by age, sex, and time of the first start on hydroxychloroquine with up to 5 controls.

“The main exposure of interest was hydroxychloroquine use, and a key strength of this study was that we utilised pharmacy dispensing records to obtain detailed information of hydroxychloroquine dose and the duration of use, and we assessed the dose in mg per day and weight-based dosing in mg per kg of body weight per day,” highlighted Dr Jorge. Candidate risk factors included age, sex, weight, diabetes, chronic kidney disease, and medication with other retinal toxins.

Among nearly 5,000 incident users, 164 cases of hydroxychloroquine retinopathy were found, of which 100 were mild in severity, 38 moderate, and 26 severe; 80% of the cases were subclassified as having the typical parafoveal and 20% the pericentral pattern. In this nested case-control study, the mean age was 56, and over 90% were women; 48% of participants took hydroxychloroquine for rheumatoid arthritis, followed by 16% due to systemic lupus erythematosus.

A conditional logistic regression identified various risk factors for retinopathy. “We observed a dose-response relationship with an increase in odds of retinopathy associated with increased weight-based dosing category. Using ≤4 mg/kg as the reference group: the odds ratio ranged from 2.76 for a dose between 4 to 5 mg/kg up to 7.36 for using ≥6 mg/kg/day,” stated Dr Jorge. She added that there were also increased odds (OR 2.96) with each additional 100 mg/day and each 5 years of use. Moreover, chronic kidney disease (≥stage 3) about doubled the odds of retinopathy. “Patients with these additional risk factors may warrant closer monitoring and this should also be a consideration when prescribing medication,“ Dr Jorge recommended.

  1. Melles RB, et al. JAMA Ophthalmol. 2014 Dec;132(12):1453-60.
  2. Fanouriakis A, et al. Ann Rheum Dis. 2019 Jun;78(6):736-745.
  3. Jorge A. Risk factors for hydroxychloroquine retinopathy and its subtypes – prospective adjudication analysis of 4,899 incident users. Abstract 0989, ACR Convergence 2021, 03–10 November.


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