The Role of Biological Therapies in the Management of Systemic Vasculitis

Abstract

Systemic vasculitides are multisystem disorders with an autoimmune basis leading to blood vessel inflammation. Vasculitis present a wide spectrum, being classified regarding different aspects on pathogenesis, histopathology or laboratory findings. The most common used classification considers size of the vessel predominantly affected, established at Chapel Hill Consensus Conference (Jennete et al, 1994): large-sized vessels (giant-cell arteritis, Takayasu’s arteritis), medium-sized vessels (polyarteritis nodosa, Kawasaki’s disease) and small-sized vessels (Wegener granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome, cryoglobulinemia, Henoch-Schonlein purpura, and cutaneous leukocytoclastic angiitis). Behcet’s disease affects small and large vessels of the arterial and venous systems. Systemic vasculitis predominantly associated with the presence of serum anti-neutrophil cytoplasmic antibodies (ANCA) are known as ANCA-associated vasculitis, in spite of about 10-20% of this vasculitis present with classical clinical picture but ANCA negative. Systemic vasculitis are rare diseases with wide and heterogenic range of manifestations, so leading prospective controlled clinical trials in pathogenesis and management of these diseases is difficult. Despite these limitations, first descriptions about vasculitis in mid-20th century ascertained that some forms of vasculitis are severe and potentially fatal in a shortterm period (weeks-months) with no treatment. These are mainly Wegener disease and microscopic polyangiits with critical organ involvement (kidney, lung, gastrointestinal system or central nervous system), but they are not the only ones. Introduction of glucocorticoids and, later, immunosuppressive agents (cyclophosphamide, methotrexate, azathioprine, etc.) contributed to achieve remission of these diseases and prevent further organ damage, former potentially fatal. But nowadays many questions are still unsolved. In ANCA-associated vasculitis, high rate of remission (about 80-90% patients) is followed by an unacceptable rate of relapses, which is especially important in Wegener granulomatosis, reaching up to 50% of patients within 2 years after the diagnosis (Hoffman et al, 1992), with further morbidity and mortality. Another concern is about cytotoxic regimens for induction of remission on these diseases: although current schemes are less toxic, severe infections and bone marrow toxicity still are major problems, so serious adverse events and mortality in early stages are not related to disease activity, but to therapy in a significant proportion of cases (Little MA et al, 2010). In last decade, the advent of target-defined drugs, known as biological agents, became a substantial advance for the management of several diseases in different medical areas, as