Hydroxychloroquine Protects Lupus Patients from Developing Seizures: Data from a Large Multiethnic Cohort

OBJECTIVE: To examine the predictors of time-to-seizure occurrence in patients with systemic lupus erythematosus (SLE) from a multiethnic US cohort.
METHODS: SLE patients (ACR criteria), age ≥ 16 years, disease duration ≤ 5 years at enrollment of African-American, Hispanic (Texan or Puerto Rican) or Caucasian ethnicity, from a longitudinal cohort were studied. All patients experiencing seizures at or after diagnosis (TD), and attributable to SLE, were included in the analyses. Variables from the different domains (socioeconomic-demographic, clinical, immunologic and genetic) were examined as potential predictors of time-to-seizure occurrence by univariable Cox proportional hazard regression analyses. Age, gender, ethnicity and those variables with p ≤ 0.10 in the univariable Cox regressions were included in the multivariable Cox proportional hazard regression analyses.
RESULTS: Six hundred patients were included in these analyses. Of them, 40 (6.7%) developed seizures at or after TD and 62.5% developed seizures within one year of SLE diagnosis. Results of the univariable and multivariable analyses are shown in the Table below.

	Univariable Analyses			Multivariable Analyses
Variable	Hazard Ratio	95% CI	p value	Hazard Ratio	95% CI	p value
Younger age, years	1.05	1.02-1.08	0.0008	1.04	1.00-1.08	0.0304
Ethnicity * Hispanic-Texan African American Caucasian	4.12 5.37 2.05	0.89-19.12 1.26-22.87 0.43-9.90	0.0736 0.0231 0.3708
Employment	0.39	0.17-0.88	0.0238
Marital status	0.52	0.28-0.99	0.0466
Disease duration	0.18	0.11-0.29	<0.0001
SLAM-R† score
TD‡	1.11	1.07-1.15	<0.0001
T0§	1.11	1.07-1.16	<0.0001	1.10	1.04-1.15	0.0004
TL¶	1.15	1.11-1.20	<0.0001
Average	1.24	1.19-1.29	<0.0001
SDI ** score
T0	1.47	1.23-1.76	<0.0001
Disease manifestations
Integument	0.20	0.11-0.38	<0.0001	0.34	0.16-0.41	0.0039
Musculoskeletal	0.09	0.04-0.21	<0.0001
Psychosis	3.85	1.20-6.80	0.0181
WHO Class IV glomerulonephritis	4.18	2.16-8.09	<0.0001
Antiphospholipid antibodies	2.87	1.26-6.52	0.0120
Medications
Hydroxychlroquine	0.18	0.01-0.34	<0.0001	0.35	0.15-0.80	0.0131
Glucocorticoids	1.03	1.01-1.05	<0.0001
Cyclophosphamide	2.54	1.36-4.74	0.0034

*Hispanic-Puerto Rican is the reference group; †Systemic Lupus Activity Measure-Revised; ‡ Diagnosis time; §Baseline; ¶ Last visit; **SLICC (Systemic Lupus International Collaborating Clinics) Damage Index.
CONCLUSIONS: Seizures tend to occur in younger individuals, early in the course of the disease and in the context of important disease activity and other serious clinical manifestations. Hydroxychloroquine appears to have a protective role in seizure occurrence, probably due to its combined anti-inflammatory, antithrombotic and antiplatelet properties. These date have practical implications for the management of lupus patients.

 L.A. González, None; R.M. Andrade, None; M. Fernández, None; M. Apte, None; L.M. Vilá, None; G. McGwin, None; J.D. Reveille, None; G.S. Alarcón, None.