Rituximab therapy for juvenile-onset systemic lupus erythematosus

Abstract

Rituximab (RTX), an anti-CD20 monoclonal antibody, has been proposed for use in the therapy of systemic lupus erythematosus (SLE). We present the initial long-term experience of the safety and efficacy of rituximab for treatment of SLE in children. Eighteen patients (mean age 14±3 years) with severe SLE were treated with rituximab after demonstrating resistance or toxicity to conventional regimens. There was a predominance of female (16/18) and ethnic African (13/18) patients. All had lupus nephritis [World Health Organization (WHO) classes 3-5] and systemic manifestations of vasculitis. Clinical disease activity of the SLE was scored with the SLE-disease activity index 2K (SLEDAI-2K). Patients were followed-up for an average of 3.0±1.3 years (range 0.5 to 4.8 years). B-cell depletion occurred within 2 weeks in all patients and persisted for up to 1 year in some. Clinical activity scores, double-stranded DNA (dsDNA) antibodies, renal function and proteinuria [urine protein to creatinine ratio (Upr/cr)] improved in 93% of the patients. Five patients required multiple courses of RTX for relapse, with B-cell repopulation. One died of infectious endocarditis related to severe immunosuppression. In conclusion, our data support the efficacy of rituximab as adjunctive treatment for SLE in children. Although rituximab was well tolerated by the majority of patients, randomized controlled trials are required to establish its long-term safety and efficacy.

Efficacy and safety of rituximab therapy for systemic lupus erythematosus: a systematic review and meta-analysis

“…Marks et al (2005) and Podolskaya et al (2008) reported that 7 patients with median age of 14.8 years received a dose of 750 mg/m 2 (about up to 100 mg, the maximum dose was 1 g) on Days 1 and 15. The participants in Nwobi et al (2008)'s study took a dose of 188 and 375 mg/m 2 . Similar to the adult patients, most of the pediatric patients were administered methylprednisolone prior to the injection of rituximab; oral prednisolone was decreased gradually after rituximab therapy.…”

“…The two studies reported five cases of herpes zoster. In Nwobi et al (2008)'s study, 14 of the 15 patients achieved complete/partial remission and decreases in SLEDAI, proteinuria, Scr, and prednisone dose. Rituximab was well tolerated in most pediatric patients.…”

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].…”

Psychiatric Illness of Systemic Lupus Erythematosus in Childhood: Spectrum of Clinically Important Manifestations

“…У всех пациентов отмечались высокая актив-ность заболевания с развитием жизнеугрожающих состоя-ний, низкая эффективность стандартных методов терапии. Согласно этим исследованиям предложено две схемы вве-дения РТМ, продемонстрировавшие свою эффективность и безопасность: 375 мг на 1 м 2 поверхности тела на протя-жении 4 последовательных недель либо 750 мг на 1 м 2 с ин-тервалом в 2 нед [90][91][92][93][94][95].…”