Background and Objectives: Belimumab (BEL) is a monoclonal antibody approved for 
the treatment of active systemic lupus erythematosus (SLE) but not for lupus 
nephritis (LN) and neuropsychiatric systemic lupus erythematosus (NPSLE). We 
aimed to assess BEL's effects on these severe, potentially life-threatening 
manifestations. Methods: Retrospective observational cohort study using routine 
clinical data in a case series of patients with SLE receiving BEL. Results: 
Sixteen patients received BEL therapy for active SLE. Nine were excluded because 
they had no LN or NPSLE. Six suffered from LN, and one patient had NPSLE. All LN 
patients received BEL in addition to standard therapy including glucocorticoids, 
hydroxychloroquine, and mycophenolate mofetil in five cases, and tacrolimus in 
one case. Three patients with proteinuria >1,000 mg/g creatinine responded well 
(one complete, two partial renal responses); all other patients had decreasing 
proteinuria and a reduction in anti-dsDNA levels. The patient with NPSLE who had 
failed previous therapies had persistent clinical improvement of cutaneous and 
neuropsychiatric manifestations. There was one mild allergic reaction and one 
lower respiratory tract infection, but no other adverse events. One patient 
discontinued therapy due to a lack of improvement in clinical symptoms, another 
because of clinical remission. Conclusions: In our series, BEL led to a decrease 
of proteinuria in patients with proteinuria of more than 1,000 mg/g creatinine 
despite standard of care treatment, and led to a marked clinical improvement in 
one patient with NPSLE. No adverse events were observed. Routinely administered 
BEL shows clinical efficacy on non-approved manifestations, but careful patient 
selection is warranted.