Background/Purpose:   Treatment with hydroxychloroquine (HCQ) is recommended for all patients with lupus nephritis to prevent further damage and reduce disease manifestations. Some studies suggest that drug levels may be important in medication efficacy. In view of reports of an increased risk of ocular toxicity with HCQ, however, the American Academy of Ophthalmology (AAO) recommends more stringent screening for damage as well as changes in dosing. Specifically, the AAO recommends dosing by ideal and not actual weight, which would decrease the dose of HCQ for many patients. To assess the impact of these dosing recommendations, we explored the patterns of HCQ use in a large patient cohort and the effect of dose levels on the trajectory of disease activity. For this purpose, we analyzed data from the Lupus Clinical Trials Consortium, Inc. (LCTC) Lupus Data Registry, a prospective registry of 1506 patients with SLE from 16 lupus centers in the US and Canada.

Methods:   Patients were consecutively enrolled into the Registry and followed at outpatient visits by participating rheumatologists.  Medication use, disease activity, and patient global assessment were recorded at each visit.  Baseline dose of HCQ was recorded as mg per kg and was analyzed as <4 mg/kg, 4-4.99 mg/kg, 5-5.99 mg/kg and ≥ 6 mg/kg, with approximately 25% of the cohort falling into each dose group.  Associations between HCQ use, disease activity, and patient global assessments were evaluated.

Results:   At the baseline visit, 1058 of the 1506 subjects (70.3%) were on HCQ. 80% of patients were on 400 mg daily, 15% on 200 mg daily with the mean dose 5.1 mg/kg.  In the 400 mg group, the mean dose was 5.4 mg/kg while the mean dose in the 200 mg group was 3.2 mg/kg. 18% of all the patients on HCQ were on more than 6.5 mg/kg. There were no significant differences in change in disease activity among any of the different mg/kg groups compared to those not on HCQ even when adjusting for baseline disease activity or only evaluating those patients with a SLEDAI of ≥4. The dose of HCQ in mg/kg was not associated with flare risk using the SELENA-SLEDAI flare instrument.  When evaluating patient global assessment of their worst score versus their baseline, those patients in the highest ≥6 mg/kg group had the smallest change in patient global assessment (p=0.02) compared to those not using HCQ suggesting better symptom control (table 1).   

Conclusion:   In this large observational cohort, there is significant variation in prescribed mg/kg dosing of HCQ. For patients on prevalent HCQ before the start of the study, the mg/kg dosing based on actual weight does not appear to impact the incidence of flare as measured by the SELENA flare instrument or overall SLE activity as measured by SLEDAI.   Together, these results suggest efficacy with HCQ occurs with various drug dosing regimens although there is some indication for a greater subjective benefit at the higher dose range.