Neuropsychiatric events occur most frequently around the time of diagnosis of systemic lupus erythematosus (SLE), according to research results published in Annals of the Rheumatic Diseases. Although these events do resolve, researchers indicated an association with reduced health-related quality of life and excess mortality.

Using data from a large, prospective, international, inception cohort of patients with SLE, researchers sought to evaluate neuropsychiatric events for attribution, outcome, and association with health-related quality of life. The study was conducted by the Systemic Lupus International Collaborating Clinics (SLICC) that included 52 investigators from 43 academic centers in 16 countries.

A total of 1827 patients were enrolled between 1999 and 2011 from the United States, Europe, Canada, Mexico, and Asia. Mean age at enrollment was 35.1±13.3 years, with 88.8% women. Mean disease duration was 5.6±4.2 months, and the mean SLE Disease Activity Index 2000 was 5.3±5.4, with a mean SLICC/American College of Rheumatology Damage Index of 0.32±0.74.

Investigators found that neuropsychiatric events occurred in 52.3% of patients; 27.0% experienced ≥2 events. Overall, there were 1910 unique neuropsychiatric events, which included all 19 neuropsychiatric syndromes, of which 1749 (91.6%) involved the central nervous system, and 161 (8.4%) involved the peripheral nervous system. Across attribution models, events attributed to SLE varied from 17.9% to 31.0%, and they occurred in 13.5% to 21.2% of patients.


Continue Reading

Investigators then used multistate models to assess the number of observed changes between neuropsychiatric states for both SLE and non-SLE events. Overall, some patients remained in the same neuropsychiatric state, while others moved through 1 or more states. For neuropsychiatric events attributed to SLE, the overall time spent in a new or ongoing neuropsychiatric state was lower and the time spent in the no neuropsychiatric state was higher (0.56 and 8.81) compared with neuropsychiatric events attributed to non-SLE causes (1.46 and 7.32, respectively).

The rate of occurrence for first neuropsychiatric events was highest in the early years, following SLE diagnosis; this result was consistent with the researchers’ modeling strategy. According to multistate models, the relative risk within the first 2 years of follow-up compared with subsequent time periods was 6.16 (95% CI, 4.96-7.66) for SLE neuropsychiatric events and 4.66 (95% CI, 4.01-5.43) for non-SLE events.

Researchers used the same multistate models to estimate the probability of patients having changed neuropsychiatric states or died across defined time periods. Among patients with no SLE neuropsychiatric event at cohort entry, there was an estimated 74% probability of remaining event-free at 10 years; among patients with neuropsychiatric events not attributed to SLE, that estimate was 48%. Estimates of dying within 10 years were elevated among patients with either new/ongoing or resolved neuropsychiatric events attributed to SLE compared with patients without SLE neuropsychiatric events (16% vs 6%; relative risk for death, 4.3; 95% CI, 2.7-6.7).

Physical and mental component summary scores indicated that patients with a new/ongoing neuropsychiatric state had clinically lower physical and mental component summary scores compared with those in the no neuropsychiatric and resolved neuropsychiatric states (P <.001).

Study limitations included the inability to detect neuropsychiatric events later in the disease course although an inception cohort study was suited to document events occurring early, the enrollment of patients from academic centers that may not reflect community practice, and the observational nature of the study.

Related Articles

“Future studies will examine in detail the predictors of transition between the [neuropsychiatric] states and the economic costs associated with [neuropsychiatric] SLE,” the researchers concluded.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Hanly JG, Urowitz MB, Gordon C, et al. Neuropsychiatric events in systemic lupus erythematosus: a longitudinal analysis of outcomes in an international inception cohort using a multistate model approach [published online January 8, 2020]. Ann Rheum Dis. doi:10.1136/annrheumdis-2019-216150