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HCQ dose and risk of hospitalization in patients with SLE

Dec 28, 2022
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Learning objective: After reading this article, learners will be able to cite a new development in systematic lupus erythematosus.

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*

Baseline characteristic, % (unless otherwise stated)

Overall
(N = 2,971)

Case-crossover study
(n = 108)

Mean age, years (SD)

44.7 (15.9)

35.9 (15.2)

Female

91.0

91.7

Race/ethnicity

 

 

              White

64.3

43.5

              Black

16.4

32.4

              Asian

6.1

5.6

              Hispanic

4.4

11.1

              Other/unknown

12.8

16.7

Mean weight, kg (SD)

72.4 (19.4)

72.1 (23.4)

Weight <80 kg

72.0

68.9

Mean height, cm

163.3 (8.3)

161.6 (8.9)

Chronic kidney disease

3.3

1.9

SLE serologies

 

 

              dsDNA antibody

43.3

82.4

              Low complement levels

46.2

82.4

SLE medications

 

 

              Glucocorticoid

15.5

13.9

              SLE immunosuppressant

8.2

9.3

dsDNA, double stranded DNA; SD, standard deviation; SLE, systematic lupus erythematosus.
*Adapted from Nestor.1

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*

HCQ dose

Case periods, n

Control periods, n

Unadjusted OR (95% CI)

Adjusted OR

(95% CI)

Weight-based dose

High dose (>5 mg/kg/day)

33

83

1.0

1.0

Low dose (≤5 mg/kg/day)

84

156

4.68 (1.66−13.20)

4.41 (1.50−12.98)

Non-weight-based dose

High dose (400 mg/day)

55

139

1.0

1.0

Low dose (<400 mg/day)

63

101

3.78 (1.51−9.51)

3.48 (1.33−9.13)

CI, confidence interval; HCQ, hydroxychloroquine; OR, odds ratio; SLE, systematic lupus erythematosus.
*Adapted from Nestor.1
Analyses adjusted for SLE disease activity index, glucocorticoid use, and SLE immunosuppressant use prior to each period.

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.

  1. Jacquelyn Nestor. Hydroxychloroquine dosing less than 5 mg/kg/day leads to increased hospitalizations for systemic lupus erythematosus flares. Oral abstract #1654. American College of Rheumatology Convergence 2022. Nov 14, 2022; Philadelphia, US.
  2. Marmor MF. The 2016 American Academy of Ophthalmology Recommendations for hydroxychloroquine dosing give accurate advice for all patients. Ophthalmol Retina. 2019;3(10):807-808. DOI: 1016/j.oret.2019.06.014