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

Figures & data

Table 1 Patient demographics

Characteristic	Entire group	No retinopathy	Retinopathy	P
Female	513 (90.8)	472 (90.1)	41 (100)	0.0246*
Renal disease	17 (3.0)	15 (2.9)	2 (4.9)	0.3535*
Liver disease	8 (1.4)	7 (1.3)	1 (2.4)	0.4536*
Both renal and liver disease	2 (0.4)	2 (0.4)	0 (0)	1.0000*
Taking tamoxifen	3 (0.5)	3 (0.6)	0 (0)	1.0000*
Weight (lbs), median (IQR)	160 (135, 189)	161 (135, 190)	135 (120, 177)	0.0026**
Height (in), median (IQR)	64 (62, 66)	64 (62, 66)	63 (62, 66)	0.1586**
IBW (lbs), median (IQR)	140 (131, 148)	140 (131, 148)	135 (131, 148)	0.1586**
Daily dose category (mg)
≤200	172 (33.1)	169 (35.0)	3 (8.6)	0.0002***
200<X<400	50 (9.6)	49 (10.1)	1 (2.9)
400	297 (57.2)	266 (55.0)	31 (88.6)
Duration of therapy (years), median (IQR)	6.2 (2.7, 11.9)	5.9 (2.5, 11.2)	12.7 (6.9, 17.2)	<0.0001**
Cumulative dose (g), median (IQR)	694 (283, 1,424)	670 (266, 1,306)	1,919 (999, 2,613)	<0.0001**
Toxic dosing using 6.5 mg/kg of IBW/d threshold, NHLBI algorithma	113 (21.8)	95 (19.7)	18 (51.4)	<0.0001*
Toxic dosing using 6.5 mg/kg of IBW/d threshold, Wolfe algorithma	225 (43.3)	198 (40.9)	27 (77.1)	<0.0001*
Toxic dosing using 5 mg/kg of RBW/d thresholda	200 (38.6)	178 (36.9)	22 (62.9)	0.0035*
BMI (kg/m^2)	27.4 (24.0, 32.5)	27.6 (24.4, 32.6)	24.0 (21.0, 31.6)	0.0103*

Notes: Data are presented as n (%) unless otherwise specified. The number of patients (denominator) for the column “Entire group” was 565, for the column “No retinopathy” was 524, for the column “Retinopathy” was 41. P, P-value from the statistical hypothesis test comparing the values in the columns “No retinopathy” and “Retinopathy”.

* Fisher’s exact test.

** Kruskal–Wallis test.

*** Chi-square (likelihood ratio) test.

a Information on daily dosing was missing for 47 of the 565 patients, of whom 41 and six patients were in the groups without and with retinopathy, respectively.

Abbreviations: BMI, body mass index; IQR, interquartile range; IBW, ideal body weight; NHLBI, National Heart Lung and Blood Institute; RBW, real body weight.

Figure 1 Receiver operating characteristic curves for hydroxychloroquine retin-opathy predicted by dosing guidelines as a univariate analysis.

Note: The red curve is the RBW method, the blue curve is the IBW method, and the green curve is the lesser of IBW and RBW methods.
Abbreviations: IBW, ideal body weight; RBW, real body weight.

Figure 2 Receiver operating characteristic curves for hydroxychloroquine retin-opathy predicted by dosing guidelines as a multivariate analysis.

Notes: Logistic regression models were fit including gender, age, cumulative dose, and BMI as common predictive variables. The red curve corresponds to the model adding guidelines based on RBW dosing, the blue curve corresponds to the model adding guidelines based on IBW dosing, and the green curve corresponds to the model adding guidelines based on the lesser of IBW and RBW dosing.
Abbreviations: BMI, body mass index; IBW, ideal body weight; RBW, real body weight.

Figure 3 Predicted risk of hydroxychloroquine retinopathy versus BMI from multivariate logistic models with a common base model including gender, age, cumulative dose, and BMI, and differing according to whether the model included dosing guidelines based on RBW (A), IBW (B), or the lesser of RBW and IBW (C).

Notes: Each point refers to a single patient. The black curve is a spline fit of predicted risk to the data points with λ (a smoothing parameter) =1,000.
Abbreviations: BMI, body mass index; IBW, ideal body weight; RBW, real body weight.

Figure 4 Predicted risk of hydroxychloroquine retinopathy versus BMI from multivariate logistic regression models as described in Figure 3.

Notes: (A) The predicted risk for the subgroups of patients taking ≥6.5 mg/kg/d (black line) and <6.5 mg/kg/d (gray line) of ideal body weight, respectively. (B) The predicted risk for the subgroups of patients taking ≥5.0 mg/kg/d (black line) and <5.0 mg/kg/d (gray line) of real body weight, respectively. The black and gray curves are spline fits of predicted risk to the data points with λ (a smoothing parameter) =1,000. The data points are not shown.
Abbreviation: BMI, body mass index.

Figure 5 Allocation of patients into zones of safer dosing by the IBW or RBW methods using the IBW algorithm published by Melles and Marmor.⁶

Notes: Each point refers to a patient. For patients who fall on the line, both methods yield the same recommended maximal safe dose. For patients who fall above the line, the RBW method yields a safer dose. For patients who fall below the line, the IBW method yields a safer dose.
Abbreviations: IBW, ideal body weight; RBW, real body weight.

Figure 6 Graph of the average weight for a woman in the age decile 50–59 years in the USA over the time span 1960–2012 from the NHANES.

Notes: The average patient taking hydroxychloroquine falls into this gender and age decile. The average weight of such a person has increased 27.5 pounds (18.8%).
Abbreviation: NHANES, National Health and Nutrition Examination Survey.

Figure 7 Risk versus body habitus based on ideal body weight and real body weight.

Notes: The data show that for obese patients (those with BMI >30), the risk of retinopathy was lower with the ideal body weight method of daily dosing compared to the real body weight method. Data from Melles and Marmor.⁶
Abbreviation: BMI, body mass index.

MellesRBMarmorMFThe risk of toxic retinopathy in patients on long-term hydroxychloroquine therapyJAMA Ophthalmol2014132121453146025275721

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