Improvement in neuropsychological function with memantine treatment among patients with systemic lupus erythematosus: a phase 2 randomised placebo-controlled clinical trial.

Abstract

Neuropsychological symptoms are common, disabling manifestations of systemic lupus erythematosus (SLE) that can persist despite immunomodulatory treatment. We evaluated whether the N-methyl-D-aspartate receptor (NMDAR) antagonist, memantine, improves cognitive function in individuals with SLE and neuropsychological dysfunction. ClearMEMory (NCT03527472) was a multisite, randomised, placebo-controlled 12-week clinical trial of memantine titrated to 40 mg/d among adults with SLE with objective neuropsychological dysfunction. The primary outcome was change in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total score from baseline to week 12. Additional outcomes included change in RBANS total score above a threshold considered clinically important (score increase ≥8) and patient global impression of change (PGI-C). Of 131 patients screened, 56 were randomised, and 43 completed primary outcome assessment and were analysed, including 18 in the memantine group and 25 in the placebo group. Improvement in RBANS total score between baseline and week 12 was greater in the memantine group (median change: +8) than the placebo group (median change: +5) (P = .032); 12 (66.7%) participants in the memantine group and 9 (36.0%) participants in the placebo group had an increase in total RBANS score ≥8 (P = .047) (number-needed-to-treat = 3.3). Using the PGI-C, 61% of participants in the memantine group and 36% of participants in the placebo group self-reported improvement (P = .19). Discontinuation due to adverse events occurred in 5 (19%) participants in the memantine group and 5 (17%) participants in the placebo group. Among patients with SLE-associated neuropsychological dysfunction, treatment with memantine for 12 weeks improved objective neuropsychological function.