Phase II ClearMEMory trial: Memantine for neuropsychiatric SLE

Results from the randomized, placebo-controlled phase II ClearMEMory (NCT03527472) trial, evaluating memantine for cognitive dysfunction in 56 adults with neuropsychiatric systemic lupus erythematosus (NPSLE), were published in Annals of the Rheumatic Diseases by Rhoads et al. The primary outcome was the change from baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total score at 12 weeks.

Key data: Among 43 patients who completed 12 weeks of treatment (memantine, n = 18; placebo, n = 25), the median maximum tolerated dose of memantine was 32.7 mg/d. Improvement in RBANS total score was significantly greater with memantine vs placebo (median change, +8 vs +5; p = 0.032). Regardless of baseline RBANS score, clinically meaningful responses (RBANS score increase ≥8) were achieved by more patients receiving memantine vs placebo (66.7% vs 36.0%). The immediate memory subscale showed the most pronounced improvement with memantine vs placebo (median change, +18.5 vs +7; p = 0.023). There were no significant differences between groups in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K; p = 0.17), Polysymptomatic Distress Scale (PSD; p = 0.94), Beck Depression Inventory-II (BDI-II; p = 0.68), or Hospital Anxiety and Depression Scale (HADS; depression, p = 0.67; anxiety, p = 0.79), though patient-reported wellbeing was greater with memantine vs placebo (61% vs 36%). 

Key learning: Memantine demonstrated clinically meaningful improvement in objective neuropsychological function and patient-reported wellbeing in adults with NPSLE, supporting further investigation in larger trials.