OP0263\u2005HYDROXYCHLOROQUINE DOSING IN PATIENTS WITH RHEUMATIC DISEASE ACROSS THE U.S.: DATA FROM THE RHEUMATOLOGY INFORMATICS SYSTEM FOR EFFECTIVENESS (RISE) REGISTRY

Abstract

Background The risk of retinal toxicity and subsequent visual loss from hydroxychloroquine (HCQ) is dependent on daily dose and duration of use. Although further efficacy and safety studies are required to understand optimal dosing strategies, real-world application of existing American Academy of Ophthalmology (AAO) recommendations in a population-based sample of patients with rheumatic disease has never been described. Objectives The objectives of this study were to assess application of AAO dosing recommendations across the U.S. and identify patient and practice-level risk factors for receiving higher than recommended doses using data from the ACR’s RISE registry. Methods RISE is a national, EHR-enabled registry that passively collects data on all patients seen by participating practices, reducing the selection bias present in single-insurer claims databases. As of December 2017, RISE held validated data from 1,257 providers in 236 practices, representing about 36% of the U.S. clinical rheumatology workforce. We included adult patients with at least one order for HCQ in 2017. For patients with multiple orders, the most recent order was included in the analysis. We excluded weights that appeared to be outliers and practices with <30 patients receiving HCQ. Instructions were interpreted to yield an average daily dose per patient. We investigated practice-level and state-level variation by calculating the proportion of patients who received a dose >5 mg/kg/day by practice and the proportion of patients who received a dose >6.5 mg/kg/day (AAO’s 2011 recommendation) by state. We tested whether prescribing a dose exceeding the AAO recommendations was associated with patient-level demographics (age, sex, race/ethnicity, insurance) or practice characteristics (type, size) using multivariate mixed-effects regression. Results We included 49,712 patients (85% female, 53% Caucasian, with mean age 57±15) from 96 practices (34% single specialty group practice, 76% with 1-5 providers). The patient average daily dose of HCQ ranged from 57 mg to 800 mg, with a median of 400 mg. Overall, 40% and 9% of patients received a HCQ dose >5 mg/kg/day and >6.5 mg/kg/day, respectively. Practice-level variation ranged from 6-66% for receiving a dose >5 mg/kg/day (Figure 1) and 0-28% for receiving a dose >6.5 mg/kg/day. State-level variation was also significant (p<0.0001, Figure 2). After adjusting for demographics and practice characteristics, low body weight (<78 kg, the sample median) was strongly associated with receiving doses >5 mg/kg/day (+64%, p<0.001) and >6.5 mg/kg/day (+18%, p<0.001). In the same model, female gender was also associated with doses >6.5 mg/kg/day (+5%, p<0.001). Practice characteristics were not statistically significantly associated with receiving a higher dose. Conclusion A significant fraction of patients with rheumatic disease on HCQ received doses greater than those recommended by the AAO, with large differences across practices and states. Patients with low body weight are consistently at increased risk of receiving a higher dose. Although further studies are required to achieve consensus on optimal dosing of HCQ, these data suggest that patients with low body weight should be targeted for toxicity monitoring regardless of the dosing cut-off used. Disclaimer: This data was supported by the ACR’s RISE Registry. However, the views expressed represent those of the authors, not necessarily those of the ACR. Reference [1] Marmor MF, Kellner U, Lai TY, et al. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision).; American Academy of Ophthalmology. Ophthalmology 2016; 123:1386–1394. Disclosure of Interests Zara Izadi Consultant for: I worked as a paid consultant for Celgene from 2014 to 2017., Milena Gianfrancesco: None declared, Michael Evans: None declared, Julia Kay: None declared, Laura Trupin: None declared, Gabriela Schmajuk Grant/research support from: Investigator initiated award from Pfizer from 2015-2018, unrelated to this work, Michelle A Petri Shareholder of: Pfizer, Merck, Grant/research support from: AstraZeneca, Exagen, Consultant for: Eli Lilly, GSK, Merck EMD Serono, Janssen, Amgen, Novartis, Quintiles, Exagen, Inova Diagnostics, AstraZeneca, Blackrock, Glenmark, UCB, and the Annenberg Center for Health Sciences, Jinoos Yazdany Grant/research support from: Pfizer, Consultant for: AstraZeneca