<>Background/Purpose: Hydroxychloroquine (HCQ) is a cornerstone of systemic lupus erythematosus (SLE) care. The major long-term adverse event risk is vision-threatening toxic retinopathy. The 2012 EULAR, 2009 Royal College of Ophthalmology, and 2011 American Academy of Ophthalmology (AAO) guidelines recommended a maximum dosing of the lower of 6.5mg/kg/day of ideal body weight (IBW) or 400 mg daily to minimize the risk of retinopathy, whereas the 2016 AAO guidelines revised this to a maximum of 5mg/kg/day of actual body weight (ABW). We assessed the trend of HCQ prescribing patterns for treating SLE in relation to these dosing guidelines over the past two decades in a general population context. Furthermore, we examined associations with purported risk factors of HCQ retinopathy.

Methods: Using a United Kingdom general population database, we conducted an incident user study of adult SLE patients, identified by Read codes, who initiated HCQ between January 1, 1996 and December 31, 2015. We examined the secular trend of the proportion of initial prescribed HCQ doses exceeding 6.5mg/kg/day IBW as well as 5mg/kg/day ABW and assessed whether excess doses according to these guidelines varied by age, sex, body mass index (BMI; lean, overweight, and obese), and chronic kidney disease (CKD; defined by a eGFR <60). 

 

Results: Of 2741 SLE patients who initiated HCQ over this 20-year period, 36.2% of the prescribed doses were > 6.5mg/kg/day IBW, and 38.12% were > 5mg/kg/day ABW. There was no significant change in the rate of initial excess dosing over time for either dose cut-off (p for trends=0.09 and 0.25, respectively) (Table 1). Women had an increased risk of excess initial dosing compared with men, with OR=12.28 (95% CI, 7.46-20.23) for IBW and 2.00 (95% CI, 1.50- 2.66) for ABW dose recommendations. Obesity was associated with a lower risk of excess HCQ dosing using ABW (OR 0.14 for obese vs. lean (95% CI, 0.10-0.18), and a higher risk of excess dosing using IBW (OR 1.30 [95% CI, 1.06-1.59]). Age had no effect on the risk of excess HCQ dosing according to either recommendation (OR 1.11; 95% CI, 0.93-1.32 for IBW, and OR=1.07, 95% CI, 0.89-1.27 for ABW). For the subgroup with available eGFR data (n=657), CKD was associated with an increased risk of excess dosing per ABW (OR 1.85, 95% CI, 1.02-3.37) after adjusting for BMI.

 

Conclusion: In this general population-based study, over one-third of SLE patients were initiated on HCQ doses exceeding both dosing guidelines, and these rates have not changed over the past two decades. This rate of excess dosing is strikingly higher among women. Obesity posed opposing risk of excess dosing between the two weight-based dosing guidelines. Furthermore, excess dosing is also higher amongst CKD patients per the recent ABW-based guidelines. These findings highlight the potential need to improve excess HCQ dosing, and call for unifying, robust, and evidence-based recommendations.