Hydroxychloroquine Dose and Hospitalizations for Active Lupus

Abstract

Objective: We sought to determine the impact of hydroxychloroquine (HCQ) dose on the risk of hospitalizations for systemic lupus erythematosus (SLE).

Methods: We conducted a case-crossover study within an academic health system, including patients with SLE who used HCQ and had ≥1 hospitalization for active SLE between January 2011 and December 2021. Case periods ended in hospitalization for SLE, whereas control periods did not. The exposures were the average weight-based HCQ dose, categorized as ≤5 or >5 mg/kg/day, and non-weight-based HCQ dose, categorized as <400 or 400 mg/day, assessed during each six-month case or control period. Odds ratios (ORs) were calculated using conditional logistic regression and adjusted for prior disease activity, kidney function, glucocorticoid use, and other immunosuppressant use.

Results: Of 2,974 patients with SLE who used HCQ (mean age 36.5 years; 92% female), 584 had ≥1 hospitalization with primary discharge diagnosis of SLE. Of these, 122 had ≥1 hospitalization for active SLE while using HCQ and had ≥1 control period with HCQ use during the study period. Lower HCQ weight-based dose (≤5 vs >5 mg/kg/day) and non-weight-based dose (<400 vs 400 mg/day) were each associated with increased hospitalizations for active SLE (adjusted OR 4.20, 95% confidence interval [CI] 1.45-12.19, and adjusted OR 3.39, 95% CI 1.31-8.81).

Conclusion: The use of lower doses of HCQ was associated with an increased risk of hospitalizations for active SLE. Although the long-term risk of HCQ retinopathy must be acknowledged, this must be balanced with the short-term and cumulative risks of increased SLE activity.

Figure 1.. Flowchart of Patients Included in the Case-Crossover Study with Inclusion and Exclusion Criteria

During the study period, patients with SLE were identified who had at least one outpatient visit with a diagnosis of SLE, and were prescribed HCQ during the study period of January, 2011-December, 2021. Of this larger cohort, patients were identified who were hospitalized with a primary discharge diagnosis for SLE (ICD-9 710.0 or ICD-10 M32.* excluding M32.0) during the study period. Patients were excluded from the case-crossover study if they were not hospitalized for active SLE, but for alternative indications such as infection, and they were excluded if they did not use HCQ during the 6-month case period prior to the hospitalization for SLE. Patients were also excluded if they did not have an eligible 6-month control period, with HCQ use and no hospitalizations for SLE, during the study period. The remaining patients were included in a case-crossover study.