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EULAR 2017 | Daily Highlights
A POPULATION-BASED STUDY ON MORTALITY AND THE INFLUENCE OF MEDICATION USE IN 4356 PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND 21845 MATCHED CONTROLS FROM THE UNITED KINGDOMAbstract: OP0039
Authors: I. E. Bultink1,*, A. Lalmohamed2,3, F. de Vries2,4
1Rheumatology, Amsterdam Rheumatology and immunology Center, VU University Medical Center, Amsterdam, 2Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, 3Clinical Pharmacy, University Medical Center Utrecht, Utrecht, 4Clinical Pharmacy and Toxicology, Maastricht University Medical Centre, Maastricht, Netherlands
Systemic lupus erythematosus (SLE) has been associated with an increased mortality rate. However, population-based data on all-cause, age-specific and sex-specific mortality risk are limited and data on the influence of medication exposure on mortality risk in SLE are scarce.
To estimate the magnitude of the risk from all-cause, age-specific, and sex-specific mortality in patients with SLE and relative risks compared with matched controls, and to evaluate the influence of medication exposure on mortality risk in SLE.
We conducted a population-based cohort study using the Clinical Practice Research Datalink (from 1987 to 2012). Each SLE patient (n=4356) was matched with up to 6 controls (n=21845) by age and sex. Multivariate Cox regression analysis estimated adjusted relative rates (RR) of mortality, and time interaction terms to evaluate mortality timing patterns. Time-dependent Cox models were used to evaluate the association of glucocorticoid use and hydroxychloroquine use on mortality and were adjusted for age, sex, lifestyle parameters, comorbidities and comedication.
A total of 442 out of 4356 SLE patients died during the study period. Patients with SLE had an increased mortality rate for all-cause mortality compared with age- and sex-matched subjects, after adjustment for confounders (adjusted RR 1.80, 95% CI 1.57-2.08). Glucocorticoid use in the previous six months raised the mortality rate while the adjusted RR was 45% decreased with low dose hydroxychloroquine use. The RR was highest in patients aged 18-39 years (adjusted RR 4.87, 95% CI 1.93-12.3) and slightly higher in females (adjusted RR 1.82, 95% CI 1.56-2.13) compared to male patients (adjusted RR 1.68, 95% CI 1.19-2.39). The mortality rate was significantly increased for patients with a history of dementia, seizures, diabetes, cancer, and renal disease (Table 1).
Table 1. Risk of all-cause mortality within SLE patients (n=4356), stratified according to organ damage (reference = no risk factor)
* Adjusted for: recent use of corticosteroids, recent use of antimalarials, recent use of benzodiazepines
Patients with SLE have a 1.8-fold increased mortality rate compared with the general population. Glucococorticoid use, female sex and young age are associated with an increased mortality risk while low dose hydroxychloroquine use significantly reduces the mortality rate. In addition, special attention should be paid to lupus patients with neuropsychiatric complications, diabetes, malignancy or renal disease since these subgroups of patients are at high risk of death.
Disclosure of Interest:
I. Bultink Grant/research support from: Lilly Netherlands, MSD, Amgen, UCB, A. Lalmohamed: None declared, F. de Vries: None declared
This very large study with almost 22 000 controls and more than 4300 patients with SLE makes a number of interesting points: It confirms positive effects of hydroxychloroquine in another population-based study. While still no randomized placebo controlled trial exists, these data and several published registry data strongly suggest the use of hydroxychloroquine in SLE patients. The study also confirms other studies showing negative predictive effects of corticosteroid use in SLE patients underlining the therapy principle of "as much as necessary, as low as possible" for the use of corticosteroids in SLE patients. It comes as no surprise that severe comorbidities such as cancer, diabetes and malignancy, as well as severe organ manifestations such as renal and neuropsychiatric involvement are associated with a bad outcome in SLE patients.
Prof. Dr. Oliver Distler