Therapy In Systemic Vasculitis Research Articles

B-cell-targeted therapy in systemic vasculitis.

The present review discusses the evidence supporting the use of B-cell-targeted therapy in the treatment of various forms of systemic vasculitis with a focus on the use of rituximab (RTX), in the antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV). Long-term follow-up of the two studies establishing the efficacy of a RTX-based induction regimen for severe AAV have demonstrated noninferiority of a single course of RTX compared with conventional therapy for remission maintenance. In addition, these observations highlight an association between relapse and B-cell reconstitution in patients treated with RTX. The maintenance of remission using rituximab in systemic ANCA-associated vasculitis trial compared a regimen of RTX infusions every 6 months to azathioprine for remission maintenance and concluded that serial RTX lead to higher rates of sustained remission.RTX is also an established therapy for cryoglobulinemic vasculitis associated with hepatitis C viral (HCV) infection. Recently published data support the long-term efficacy and safety of RTX for cryoglobulinemic vasculitis. B-cell depletion with RTX is an established therapy for both remission induction and maintenance in severe AAV and in HCV-related cryoglobulinemic vasculitis. There are limited data to support use of B-cell-targeted therapy in refractory cases of other forms of systemic vasculitis such as eosinophilic granulomatosis with polyangiitis and Takayasu's arteritis.

Biologic therapy in primary systemic vasculitis of the young

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.

Vasculitis and infection: effects of immunosuppressive therapy

The immunosuppressive therapy in systemic vasculitis leads to immunological dysfunctions. The consequences of granulocytopenia and cellular immune deficits are infections of different etiologies in up to 50% of vasculitis patients. The leading severe infections are sepsis and pneumonia induced by a broad spectrum of pathogens (extra- and intra-cellular growing bacteria, fungi, parasites and viruses). The contribution of infections to the mortality of vasculitis patients is important and should induce early and careful control of these events.

Percutaneous management of occlusive arterial disease associated with vasculitis: a single center experience.

The purpose of this study was to evaluate the safety and effectiveness of percutaneous transluminal angioplasty for occlusive arterial disease associated with vasculitis. Eleven patients (10 women, 1 man; ages 35-82 years) with the diagnosis of vasculitis of the large vessels underwent interventional treatment during intraarterial angiography. The causes included giant cell arteritis (n = 8) and Takayasu arteritis (n = 3). Thirty-three occlusive lesions (including brachiocephalic and renal arteries, and arteries of upper and lower extremities) were treated with balloon angioplasty and/or stent placement. Follow-up included clinical examination, angiography, and color duplex ultrasound. Technical success was 100% (25/25) for stenoses and 50% (4/8) for occlusive lesions, representing all lesions combined from different anatomic locations. Dissection (n = 3) and arterial rupture with retroperitoneal hematoma (n = 1) was found in three patients. During follow-up (mean 12 months), restenoses (n = 8) and re-restenoses (n = 1) occurred in 8 vascular areas. Three of these lesions were treated with repeated PTA (n = 4). The cumulative primary clinical success rate was 67.6%, cumulative secondary success rate 74.4%, and cumulative tertiary success rate 75.9%. Interventional therapy in systemic vasculitis provides promising results in technical success rates and followup. Angioplasty may result in arterial injury, but the rate of complications is low.

Chronic immunosuppressive therapy for systemic vasculitis.

Treatment with glucocorticoids and cytotoxic agents has markedly improved the outcome in patients with systemic vasculitis. As more patients survive with these disorders, the long-term risks of these therapies have become increasingly apparent. An understanding of therapeutic toxicities is important because in some instances they can be minimized by the use of treatment strategies and monitoring techniques. Pneumocystis carinii pneumonia is associated with a high mortality rate in immunosuppressed patients but can be prevented by prophylaxis. Glucocorticoid-related avascular necrosis can incur morbidity affecting employment and daily function. Although treatment options remain limited, investigation into joint salvage procedures has continued. The frequency and longevity of urologic toxicity associated with cyclophosphamide therapy have recently been addressed. Identification of this risk has led to the development of long-term monitoring strategies in cyclophosphamide-treated patients.

Etoposide: more effective and less bone-marrow toxic than standard immunosuppressive therapy in systemic vasculitis?

Etoposide: more effective and less bone-marrow toxic than standard immunosuppressive therapy in systemic vasculitis?

Etoposide: more effective and less bone-marrow toxic than standard immunosuppressive therapy in systemic vasculitis?

In two patients suffering from ANCA-positive systemic vasculitis (one from Wegener's granulomatosis, the other from microscopic polyangiitis), who were both resistant to or could not tolerate standard immunosuppressive therapy, complete clinical and biochemical remission was obtained within few months, treating with cyclic etoposide. Etoposide therapy was found to be significantly less bone marrow toxic than standard immunosuppressive therapy.