Somatotype, the risk of hydroxychloroquine retinopathy, and safe daily dosing guidelines

Abstract

PurposeThe aim of this study was to determine whether somatotype influences the risk of hydroxychloroquine (HC) retinopathy (HCR) and whether dosing by real body weight (RBW), ideal body weight (IBW), or the lesser of these better predicts the risk of HCR.Patients and methodsA total of 565 patients taking HC for whom height and weight were recorded and a sensitive ancillary testing modality was used including 10-2 visual fields, spectral domain optical coherence tomography, fundus autofluorescence imaging, and multifocal electroretinography were enrolled. Body mass index (BMI) was compared for patients without and with HCR. Logistic regression models of age, cumulative dose, and daily dosing based on RBW, IBW, or lesser of these were compared. Area under the curve (AUC) of receiver operating characteristic plots was used to assess the diagnostic accuracy of RBW, IBW, and lesser of these guidelines for safe dosing. Probability plots for the risk of retinopathy versus BMI were compared for the different recommended guidelines on safe dosing.ResultsA total of 41 patients had HCR. The median BMI was 27.6 (interquartile range [IQR] 24.3, 32.6) and 24.0 (IQR 21.0, 31.6) for patients without and with HCR (P=0.0102), respectively. AUC for univariate receiver operating characteristic plots of retinopathy versus dosing by RBW, IBW, and lesser of these was 0.71, 0.72, and 0.76, respectively. AUC for multivariate receiver operating characteristic plots of retinopathy versus models incorporating gender, age, cumulative dose, and BMI and differing by including dosing by RBW, IBW, and lesser of these was 0.82, 0.82, and 0.83, respectively. For all of the multivariate logistic models, the risk of retinopathy was higher for lower BMIs.ConclusionShort, asthenic women are at higher risk for HCR. The 2011 American Academy of Ophthalmology (AAO) guidelines are safer for short, obese women. The 2016 AAO guidelines are safer for short, asthenic patients. Choosing daily dosing based on the lesser of the RBW and IBW guidelines is safer for all patients.

Toxicity of chloroquine and hydroxychloroquine following therapeutic use or overdose

“…The incidence of retinopathy differs based on year and screening modality used. Compared with early estimates suggesting low risk with standard drug doses [90], studies using modern screening techniques report retinopathy prevalence of up to 8% [91,92]; however, limitations exist to this literature base [89]. The risk of retinopathy is higher with increasing age, dose, and duration of usage [91,[93][94][95].…”

American College of Rheumatology, American Academy of Dermatology, Rheumatologic Dermatology Society, and American Academy of Ophthalmology 2020 Joint Statement on Hydroxychloroquine Use With Respect to Retinal Toxicity

“…In recent representative studies, the prevalence of HCQ retinopathy has been reported to range from 4.3% to 13.8% (4)(5)(6)(7)(8). These studies cannot be directly compared, because they vary in many important aspects, including the number of participants who have taken HCQ for 10 years or longer.…”

Systemic toxicity of chloroquine and hydroxychloroquine: prevalence, mechanisms, risk factors, prognostic and screening possibilities

“…However, it affects 3.1% of patients treated for more than 20 years. The prevalence of retinal toxicity assessed by more modern and sensitive methods such as spectral-domain optical coherence tomography (SD-OCT) and 10-2 visual field analyser (VFA)is much higher, estimated at 7.5% [24 , 25] . More precisely, this toxicity is estimated at less than 2% within the first 10 years of use but at almost 20% after 20 years of use [24] .…”

“…More precisely, this toxicity is estimated at less than 2% within the first 10 years of use but at almost 20% after 20 years of use [24] . The daily dose of 4-AQ plays a major role since patients treated with more than 5 mg/kg/day have 5–7 times more toxicity [24 , 25] .…”