Use of Rituximab in Childhood Idiopathic Nephrotic Syndrome

Abstract

Rituximab is an established therapy in children with idiopathic nephrotic syndrome to sustain short to medium term disease remission and avoid steroid toxicities. Recent trials focus on its use as a first-line agent among those with milder disease severity. Rituximab is used in multi-drug refractory nephrotic syndrome and post-transplant disease recurrence, although the evidence is much less substantial. Available data suggest that the treatment response to rituximab depends on various patient factors, dosing regimen and the concomitant use of maintenance immunosuppression. Following repeated treatments, patients are found to have an improving response overall with longer relapse-free period. The drug effect, however, is not permanent and 80% of patients eventually relapse and many will require an additional course of rituximab. This underpins the importance to understand the long-term safety profile upon repeated treatments. Although rituximab appears to be generally safe, there are concerns of long-term hypogammaglobulinaemia, especially in young children. Reliable immunophenotyping and biomarkers are yet to be discovered to predict treatment success, risk of both rare and severe side-effects, persistent hypogammaglobulinaemia and to guide on re-dosing strategy. In this review, we highlight recent advances on the use of rituximab for childhood nephrotic syndrome and how the therapeutic landscape is evolving.

Rituximab in idiopathic nephrotic syndrome: still waiting for stronger evidences

“…According to these recommendations, RTX is indicated as a second-line option to be considered after a course of treatment with at least one other SSA. This differs from the stance of some authors who advocate for RTX as a first-line option, particularly in patients with milder disease who may potentially respond to steroids or other better-established SSA options 5 .…”

“…Therefore, traditional clinical characterization based on the initial response to corticosteroid therapy, number of relapses over time, or steroid dependence may not adequately delineate homogeneous groups in terms of disease pathogenesis and, consequently, therapeutic responses. Furthermore, the relatively recent use of RTX as a treatment option has led to substantial variations in treatment schedules, including differences in dosage, number of infusions, maintenance medications following RTX, duration of follow-up, and criteria for selecting cases 5 .…”

“…Despite the complexity of the literature, Chan et al 5 conducted an extensive review that identified factors associated with the efficacy of RTX treatment in INS. The review found that improved treatment outcomes were associated with older age at the time of RTX administration, white ethnicity in children, utilization of maintenance medications following RTX, repeated courses of RTX, and favorable baseline immunologic profiles (including a higher number of circulating regulatory T-cells and lower mitogen-stimulated T-cell subsets) 5 . Conversely, steroid resistance, dependence on multiple medications, low RTX dosage without concurrent maintenance medication, and rapid repopulation of total memory B cells were associated with a higher risk of relapse.…”

Rituximab na síndrome nefrótica idiopática: ainda à espera de evidências mais robustas

“…Portanto, a caracterização clínica tradicional baseada na resposta inicial à terapia com corticosteroides, no número de recidivas ao longo do tempo ou na dependência de esteroides pode não delinear adequadamente grupos homogêneos em termos de patogênese da doença e, consequentemente, respostas terapêuticas. Além disso, o uso relativamente recente do RTX como opção de tratamento levou a variações substanciais nos esquemas de tratamento, incluindo diferenças na dosagem, número de infusões, medicamentos de manutenção após o RTX, duração do acompanhamento e critérios de seleção de casos 5 .…”

“…Apesar da complexidade da literatura, Chan et al 5 realizaram uma extensa revisão que identificou fatores associados à eficácia do tratamento com RTX na SNI. A revisão constatou que os melhores desfechos do tratamento foram associados à idade mais avançada no momento da administração do RTX, etnia branca em crianças, uso de medicamentos de manutenção após o RTX, cursos repetidos de RTX e perfis imunológicos basais favoráveis (incluindo um número maior de células T reguladoras circulantes e subconjuntos menores de células T estimuladas por mitógenos) 5 . Por outro lado, a resistência a esteroides, a dependência de múltiplos medicamentos, a baixa dosagem de RTX sem medicação de manutenção concomitante e a rápida repopulação do total de células B de memória foram associadas a um maior risco de recidiva.…”