Male Sex, Neuropsychiatric Damage Associated With Increased Risk for NPSLE Flare

The male sex, neuropsychiatric systemic lupus erythematosus (NPSLE), and neuropsychiatric damage predicts risk for NPSLE flare, according to study results published in Rheumatology.  

Researchers conducted a post-hoc analysis using data from 5 phase 3 randomized controlled trials of belimumab (BLISS-52, BLISS-76, BLISS-NEA, BLISS-SC, and EMBRACE).

Adult participants were eligible to be included in the study if they met the American College of Rheumatology (ACR) criteria.  In addition, eligible patients had an ANA titer of at least 1:80 and/or a serum anti-dsDNA antibody level of 30 IU/mL or more at screening, and a Safety of Estrogens in Lupus National Assessment (SELENA)-SLEDAI score of at least 6.

In total, 3638 patients with SLE were included in the study. In the BLISS-52 and BLISS-76 studies, patients were assigned randomly to receive intravenous (IV) belimumab 1 mg/kg, IV belimumab 10 mg/kg, or placebo, in addition to nonbiologic standard therapy. In the BLISS-NEA and EMBRACE studies, patients received IV belimumab 10 mg/kg or placebo, along with standard therapy. In the BLISS-SC study, patients received weekly subcutaneous doses of belimumab 200 mg or placebo, plus standard therapy.

Organ damage was evaluated using the Systemic Lupus International Collaborating Clinics (SLICC)/ACR Damage Index (SDI).

Throughout the 52-week follow-up period, a total of 105 (2.9%) patients experienced an NPSLE flare. In a multivariable analysis, several factors were found to be strongly associated with the occurrence of an NPSLE flare. The factors included male sex (hazard ratio [HR], 2.37; 95% CI, 1.31-4.28; P =.004), baseline NP BILAG B-D (HR, 5.91; 95% CI, 3.86-9.06; P <.001), and increasing SDI scores (HR, 1.35; 95% CI, 1.21-1.50; P <.001). Of note, the use of belimumab at any dosage or administration form did not show an association with NPSLE flares. 

Neuropsychiatric damage was the strongest determinant of NPSLE flare (HR, 3.25; 95% CI, 2.72-3.88; P <.001), which was consistent for cognitive impairment (HR, 14.29; 95% CI, 9.22-22.14; P <.001), traverse myelitis (HR, 21.89; 95% CI, 5.40-88.72; P <.001), and neuropathy (HR, 8.87; 95% CI, 5.59-14.09; P <.001). In addition, researchers determined that male sex had the greatest impact as a determinant for de novo NPSLE flare (HR, 3.26; 95% CI, 1.51-7.04; P =.003).

A limitation of the study was its post-hoc design, which may have restricted the statistical power of the analyses. Another limitation included the specific population of patients with SLE, which could have limited the generalizability of the findings.

Researchers concluded, “[W]e showed that male sex, current or previous NPSLE activity, and established organ damage in the NP domain were robust determinants of NPSLE flare development in [patients with] SLE treated for active disease yet no ongoing severe NP involvement.”

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.