HCQ dose and risk of hospitalization in patients with SLE

Hydroxychloroquine (HCQ) is a first-line treatment for patients with systematic lupus erythematosus (SLE) and its use is associated with a reduced risk of lupus flares, improved survival, and decreased cardiovascular and renal events.¹

However, long-term use of HCQ is associated with increased risk of retinopathy.¹ HCQ dosing has been examined in recent years with a reduction to <5 mg/kg/day recommended in the 2016 American Academy of Ophthalmology Guidelines,² which would have decreased the dose for many patients who had previously been given 400 mg/day.

During the ACR Convergence 2022, Nestor¹ presented data on whether this reduction in HCQ dosing leads to an increase in flares requiring hospitalization in patients with SLE compared with traditional doses.

Study design

This was a case-crossover study using data from the Massachusetts General Brigham SLE cohort. Patients were selected as indicated in Figure 1.

Both the case and the control periods were 6 months long (Figure 1). The control period was a 6‑month period that did not end in hospitalization for SLE, whereas patients were hospitalized at the end of the 6-month case period. Up to three case periods and three control periods were allowed as part of the study, with preference given to control periods before the case period.

Figure 1. A Patient selection schema and B study design* 

HCQ, hydroxychloroquine; SLE, systematic lupus erythematosus.
*Adapted from Nestor.^1
†Both the case and control groups received HCQ.

The HCQ exposures examined included weight-based HCQ dosing (either low dose [≤5 mg/kg/day] or high dose [>5 mg/kg/day]) and non-weight-based (low dose [<400 mg/day] or high dose [400 mg/day]).

Results

Baseline characteristics for the whole cohort and the ones included in the case-crossover study are shown in Table 1. While the majority of patients in the total cohort were white (64.3%), in the case-crossover study there was an increase in the proportion of Black patients (32.4% in the case-crossover study vs 16.4% in the overall study) and Hispanic patients (11.1% in the case-crossover study vs 4.4% in the overall study).

Most patients (68.9%) weighed <80 kg in the case-crossover study and therefore should receive <400 mg/day HCQ according to current ophthalmology guidelines.

Table 1. Baseline patient characteristics*

The low-dose HCQ doses in both the weight-based and non-weight-based groups were associated with an increased odds ratio for hospitalization for SLE (Table 2).

Table 2. Odds ratio analysis for different dosing groups*

This study had some limitations. Complete adherence to HCQ treatment was not monitored (e.g., dispensing records) and alternative reasons for lower HCQ dosing such a gastrointestinal or renal issues were also not accounted for; however, Nestor commented that chronic kidney disease prevalence was low in the study population.

Conclusion 

This case-control study found that lower doses of HCQ were associated with an increased risk of hospitalization in patients with SLE. As a result of these data, the dosing of HCQ may need to be reexamined. Retinopathy is a side effect of long-term HCQ use, and while flares may be short-term, they result in increased organ damage. In addition, treatment of flares with other agents, such as glucocorticoids, can result in increased side effects. The speaker suggested that in order to overcome the risk of lupus flare resulting in hospitalization, increased HCQ dosing could be utilized earlier in the disease course or in those patients with more active disease.