Safety and efficacy of Rituximab in refractory pediatric systemic lupus erythematosus nephritis: a single-center experience of Northern Greece

Abstract

Lupus nephritis (LN) is the major determinant of outcome in pediatric systemic lupus erythematosus (pSLE), and its treatment remains a challenge. The aim of this study was to report the experience of our center in treating with rituximab (RTX) SLE patients with severe LN. Four pSLE patients with biopsy-proven LN, who are refractory to conventional immunosuppressive treatment, received four doses of 375-500 mg/m(2) RTX, 2-3 weeks apart. All patients were concurrently receiving corticosteroids (CSs) and mycophenolate mofetil. Patients' clinical and laboratory findings were recorded at RTX initiation, after each infusion and at 3.4 ± 2.1 month intervals thereafter. pSLE activity was assessed using the European Consensus Lupus Activity Measurement (ECLAM), while LN activity using 24-hour urine protein excretion and serum cystatin C. Patients were followed up for 6-21 months (median: 16 months). Full Β-cell depletion was noticed 2-4 weeks after RTX initiation and lasted 4-7 months. All patients achieved complete LN remission 3.5 months (range: 2-4) after RTX initiation, which was retained in 3 patients through the follow-up period. One patient relapsed 15 months after RTX initiation and received one additional RTX dose. ECLAM scores and CSs doses were markedly reduced in all patients, while complement levels were increased. No side effects or infections were observed. In conclusion, RTX is an alternative, safe and efficient treatment for refractory LN.

Available evidence and outcome of off-label use of rituximab in clinical practice

“…Two clinical trials with rituximab in patients with lupus have not confirmed the efficacy suggested by case-series and recent cohort studies [6][7][8][9][10][11][12]. In the EXPLORER trial that included patients with moderately-to-severely active systemic lupus erythematosus, no differences in the proportion of patients achieving and maintaining a partial or complete response were found between rituximab and placebo [25].…”

“…Although several authors have analyzed the off-label use of rituximab in patients with specific diseases, mainly systemic lupus erythematosus, lupus nephritis and other severe refractory systemic autoimmune diseases [6][7][8][9][10][11][12], data on its use in different off-label indications are scarce [13][14][15]. The aim of this study was to analyze the indications for off-label use of rituximab in our centres, the available evidence when it was used, the outcomes of treated patients, as well as the cost.…”

Safety and Efficacy of Rituximab in Childhood-onset Systemic Lupus Erythematosus and Other Rheumatic Diseases

“…Although only 15-20% of cases are diagnosed in childhood, SLE has a more severe phenotype in children compared to adults, particularly in those with nonwhite ethnicity 7,8,9 . Several open-label studies of RTX in pediatric subjects have demonstrated benefit in life-threatening or organ-threatening SLE 5,10,11,12,13,14,15 . However, limitations of these studies include low patient numbers and demographic cohorts not representative of many patients with SLE in the United States.…”

Experience in Rituximab Administration in Children with Systemic Lupus Erythematosus: a Retrospective Study of the Case Series

“…Вопрос применения ритуксимаба в схемах терапии СКВ остается открытым. С одной стороны, в единичных слу-чаях, а также при анализе серии клинических наблю-дений показана эффективность препарата у пациентов с очень высокой активностью СКВ, резистентных к пред-шествующей терапии и высоким риском летального исхода [38][39][40]. С другой стороны, в немногочисленных ретроспективных исследованиях нет указаний на суще-ственное превосходство схем с применением ритукси-маба по отношению к схемам лечения без него [41,42].…”