Biologic therapy in primary systemic vasculitis of the young

Rheumatology Department, Institute of Child Health, London, UK.
Rheumatology (Oxford, England) (Impact Factor: 4.48). 07/2009; 48(8):978-86. DOI: 10.1093/rheumatology/kep148
Source: PubMed


To describe the biologic treatment regimens and report the efficacy and safety of biologic therapies in a multicentre series of children with primary systemic vasculitis (PSV).
This was a retrospective descriptive case series of children with PSV treated with biologic therapy between February 2002 and November 2007. Primary retrospective outcome assessment measures were: daily corticosteroid dose; Birmingham Vasculitis Activity Score (BVAS); and adverse events (including infection rate).
Twenty-five patients median age 8.8 (range 2.4-16) years; 11 male with active PSV (n = 6 with anti-neutrophil cytoplasmic antibody associated vasculitides, n = 11 with polyarteritis nodosa, n = 7 with unclassified vasculitis and n = 1 with Behçet's disease) were treated with biologic agents including infliximab (n = 7), rituximab (n = 6), etanercept (n = 4), adalimumab (n = 1) or multiple biologics sequentially (n = 7). Overall, there was a significant reduction in BVAS from a median of 8.5 (range 5-32) at start of therapy to 4 (range 0-19) at median 32 months follow-up (P = 0.003) accompanied by significant reduction in median daily prednisolone requirement from 1 (range 0.2-2) to 0.25 (range 0-1) mg/kg/day, P = 0.000. For those receiving multiple biologic agents sequentially, a similar clinical improvement was observed with corticosteroid sparing. Infections occurred in 24%, the most severe in those receiving infliximab.
Our data provide retrospective evidence of efficacy of these agents, and highlight the associated infectious complications. Further multicentre standardization of treatment protocols and data collection to inform clinical trials of biologic therapy in systemic vasculitis of the young is required.

Download full-text


Available from: Kjell Tullus, Oct 05, 2015
34 Reads
  • Source
    • "Concerning refractory cases, potential efficacy of intravenous Ig were reported in recent studies [10], while some other studies report successful outcomes using biologic agents as infliximab or rituximab [11]. Gianviti et al., discussed the possible benefit from the addition of plasma exchange to immunosuppressive medication in life-threatening situations, nevertheless still further trial are needed to resolve the question of this procedure's value in treating childhood vascular diseases [12]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Central nervous system vasculitides in children may develop as a primary condition or secondary to an underlying systemic disease. Many vasculitides affect both adults and children, while some others occur almost exclusively in childhood. Patients usually present with systemic symptoms with single or multiorgan dysfunction. The involvement of central nervous system in childhood is not frequent and it occurs more often as a feature of subtypes like childhood polyarteritis nodosa, Kawasaki disease, Henoch Schönlein purpura, and Bechet disease. Primary angiitis of the central nervous system of childhood is a reversible cause of severe neurological impairment, including acute ischemic stroke, intractable seizures, and cognitive decline. The first line therapy of CNS vasculitides is mainly based on corticosteroids and immunosuppressor drugs. Other strategies include plasmapheresis, immunoglobulins, and biologic drugs. This paper discusses on current understanding of most frequent primary and secondary central nervous system vasculitides in children including a tailored-diagnostic approach and new evidence regarding treatment.
    Clinical and Developmental Immunology 09/2012; 2012(4):698327. DOI:10.1155/2012/698327 · 2.93 Impact Factor
  • Source
    • "Studies on uveitis have included a few patients with Behçet’s Disease, whose inflammatory eye disease responded to adalimumab.40 While there is more experience on the use of infliximab and etanercept,49 there have been reports on adalimumab-responsive pediatric Behçet’s Disease patients; one patient with neuro-Behçet’s Disease showed clinical and MRI improvement.54,55 "
    [Show abstract] [Hide abstract]
    ABSTRACT: Treatment of children and adolescents with juvenile idiopathic arthritis and other pediatric rheumatic diseases has evolved. Where once there was only a limited arsenal of medications, with significant side effects and inadequate efficacy, today, with an increased understanding of the pathogenesis of these diseases, there is a wider variety of more targeted and effective treatments. TNF-α is a cytokine involved in a number of inflammatory pathways in pediatric rheumatic diseases. The emergence of biologic modifiers that target TNF-α has been pivotal in providing the ability to deliver early and aggressive treatment. Adalimumab, a recombinant monoclonal antibody to TNF-α, is an important therapeutic option, which affords children and adolescents with chronic illnesses an improved quality of life.
    Adolescent Health, Medicine and Therapeutics 06/2012; 3:85-93. DOI:10.2147/AHMT.S22607
  • Source
    • "This was associated with a significant reduction in oral steroid requirement from 1.0 to 0.25 mg/kg/day. Notably, the overall rate of infection was 24%, but was more severe in those receiving infliximab [14]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Primary systemic vasculitis presenting in childhood is an uncommon but serious condition. As these patients transfer to adult clinics for continuing care, defining long term outcomes with emphasis on disease and treatment- related morbidity and mortality is important. The aim of this study is to describe the long- term clinical course of paediatric patients with ANCA vasculitis. The adult patients in our vasculitis clinics who had presented in childhood, with a follow up time of greater than 10 years were included. We also reviewed the literature for articles describing the clinical outcome of paediatric patients with ANCA vasculitis. We describe the clinical course of 8 adults who presented in childhood with ANCA vasculitis. 7 patients had Wegener's granulomatosis and 1 had microscopic polyangiitis. The median age at presentation was 11.5 years, and follow up time ranged form 11 to 30 years. Induction therapy for all patients was steroids and/or cyclophosphamide. Maintenance therapy was with azathioprine or mycophenolate mofetil. Biological agents were used in 3 patients for relapsed disease in adulthood only.Seven patients achieved complete remission. All patients experienced disease relapse, with a median of 4 episodes. Kidney function was generally well preserved, with median eGFR 76 ml/min. Only one patient developed end-stage renal failure and one patient died after 25 years of disease. Treatment-related morbidity rates were high; 7 suffered from infections, 4 were infertile, 2 had skeletal complications, and 1 developed malignancy. Close long- term follow up of paediatric patients with ANCA vasculitis is imperative, as this patient cohort is likely to live long enough to develop significant treatment and disease- related morbidities. Prospective cohort studies with novel therapies including paediatric patients are crucial to help us determine the best approach to managing this complex group of patients. In addition, although not yet observed in our series, late cardiovascular morbidity remains a major longer-term potential concern for adult survivors of paediatric vasculitis.
    Pediatric Rheumatology 06/2011; 9(1):12. DOI:10.1186/1546-0096-9-12 · 1.61 Impact Factor
Show more