Efficacy and safety of belimumab/low-dose cyclophosphamide therapy in moderate-to-severe systemic lupus erythematosus

Abstract

ObjectivesWe have reported previously that Belimumab, a human monoclonal antibody that inhibits B-cell activating factor(BAFF) could be an effective and safe option to treat Neuropsychiatric manifestations of SLE (NPSLE). To avoid inadequate efficacy of Belimumab and significant adverse events of often-used dose of cyclophosphamide (CYC) for SLE, we evaluated the efficacy, safety, and possible immune mechanisms of Belimumab treatment in combination with intermittent low-dose intravenous CYC for moderate-to-severe SLE.MethodsIn this non blinded and parallel-group trial, we collected 82 cases of moderate-to-severe SLE patients, 40 received Belimumab treatment and 42 received conventional treatments as historical controls for 24 weeks. The demographic features, clinical manifestations, and laboratory indicators including peripheral blood lymphocyte subgroups or subsets were compared before and after the treatments.ResultsCompared with the baseline, 6 months post Belimumab group treatment, disease activity score SLEDAI (13.78 to 3.82, P<0.05) and BILAG scores (16.40 to 5.48, P<0.05) were reduced; C3 (0.19 to 1.14, P<0.05) and C4 (0.04 to 0.22, P<0.05) increased; the absolute numbers of B and T cells were the first decreased and then significantly increased, tended to balance. Moreover, Belimumab group treatment significantly reduced the serum levels of IL-6, the ratio of B and T cells, and the proportion of infections and menstrual disorders.ConclusionCompared with conventional treatment, Belimumab with low-dose intravenous CYC significantly reduced disease activity scores and maintained the B/T cell balance for SLE patients at 24 weeks. It was more efficacy and safe (adverse events such as infection were significantly lower). It should be the mechanism that Belimumab combined with low-dose intravenous CYC therapy restores the balance of T and B cells, which proposes a potential treatment strategyfor SLE.

Mental disorders in children with rheumatic diseases

“…Принимая во внимание важное значение ИФН 1-го типа в генезе хронических прогрессирующих форм нейролюпуса, перспективным представляется применение в терапии СКВ с ювенильным дебютом ингибитора ИФН 1-го типа анифролумаба [21,63], а с учетом заметной роли аутореактивных эффекторных лимфоцитов в генезе острой агрессивной формы нейролюпуса в реальной клинической практике активно используются анти-В-клеточные ГИБП ритуксимаб [64][65][66] и белимумаб [67,68]. С другой стороны, нельзя не упомянуть о том, что при использовании белимумаба у взрослых статистически значимо чаще, чем у детей, фиксировались депрессия, суицидальные мысли и поведенческие нарушения [69].…”

B cell metabolism in autoimmune diseases: signaling pathways and interventions

“…Compared to conventional treatment, the combination of belimumab and low-dose intravenous cyclophosphamide (CYC) therapy presents a remarkable restoration of T and B cell equilibrium and significantly reduces disease activity scores among patients diagnosed with SLE. This treatment also significantly reduces adverse events such as infections ( 56 ).…”