J Jpn Coll Angiol, 2009, 49: 75 79

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1 Online publication June 24, 2009 ANCA TNF-α CD20 J Jpn Coll Angiol, 2009, 49: ANCA-associated vasculitis, Takayasu s arteritis, TNF-α-antagonists, rituximab Wegener NIH TNF-α B 3 Wegener 2 2mg/kg/ 0.5 1mg/kg/ MTX 25mg/ 0.25mg/kg/ MTX mg/dl MTX 2mg/kg/ THE JOURNAL of JAPANESE COLLEGE of ANGIOLOGY Vol. 49,

2 25mg Wegener Wegener TNF-α 1 TNF-α 3 TNF TNF-α Crohn Wegener Wegener Wegener mg/ kg Booth 9) ANCA 10 Wegener 3 9 5mg/kg 6 5 BVAS DNA Wegener mg/kg 375mg/m B 1 1 B 9 2 ANCA ANCA Vol. 49, 2009

3 13 ANCA 3 Wegener 1 α MTX TNF-α 14) 13 MTX 7 25mg mg/kg mg mg/ TNF-α 0mg 0 20mg/ TNF-α mg 2 50mg mg/kg IL-6 Castleman 20 1 TNF-alpha TNF-alpha RCT 2 1 5mg/ kg mg mg/ mg 20mg/ 2 2.5mg 10mg/ TNF-α IL-6 IL-6 Vol. 49,

4 1 Leib ES, Restivo C, Paulus HE: Immunosuppressive and corticosteroid therapy of polyarteritis nodosa. Am J Med, 1979, 67: Fauci AS, Haynes BF, Katz P et al: Wegener s granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years. Ann Intern Med, 1983, 98: ) Wegener s Granulomatosis Etanercept Trial (WGET) Research Group: Etanercept plus standard therapy for Wegener s granulomatosis. N Engl J Med, 2005, 352: ) Knight A, Askling J, Ekbom A: Cancer incidence in a population-based cohort of patients with Wegener s granulomatosis. Int J Cancer, 2002, 100: ) Pankhurst T, Savage CO, Gordon C et al: Malignancy is increased in ANCA-associated vasculitis. Rheumatology (Oxford), 2004, 43: ) Booth AD, Jefferson HJ, Ayliffe W et al: Safety and efficacy of TNFα blockade in relapsing vasculitis. Ann Rheum Dis, 2002, 61: ) Bartolucci P, Ramanoelina J, Cohen P et al: Efficacy of the anti-tnf-α antibody infliximab against refractory systemic vasculitides: an open pilot study on 10 patients. Rheumatology (Oxford), 2002, 41: ) Lamprecht P, Voswinkel J, Lilienthal T et al: Effectiveness of TNF-α blockade with infliximab in refractory Wegener s granulomatosis. Rheumatology (Oxford), 2002, 41: ) Booth A, Harper L, Hammad T et al. Prospective study of TNFα blockade with infliximab in anti-neutrophil cytoplasmic antibody-associated systemic vasculitis. J Am Soc Nephrol, 2004, 15: ) Sangle SR, Hughes GR, D Cruz DP: Infliximab in patients with systemic vasculitis that is difficult to treat: poor outcome and significant adverse effects. Ann Rheum Dis, 2007, 66: ) Keogh KA, Wylam ME, Stone JH et al: Induction of remission by B lymphocyte depletion in eleven patients with refractory antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum, 2005, 52: ) Keogh KA, Ytterberg SR, Fervenza FC et al: Rituximab for refractory Wegener s granulomatosis: report of a prospective, open-label pilot trial. Am J Respir Crit Care Med, 2006, 173: ) Stasi R, Stipa E, Del Poeta G et al: Long-term observation of patients with anti-neutrophil cytoplasmic antibodyassociated vasculitis treated with rituximab. Rheumatology (Oxford), 2006, 45: ) Hoffman GS, Merkel PA, Brasington RD et al: Anti-tumor necrosis factor therapy in patients with difficult to treat Takayasu arteritis. Arthritis Rheum, 2004, 50: ) Della Rossa A, Tavoni A, Merlini G et al: Two Takayasu arteritis patients successfully treated with infliximab: a potential disease-modifying agent? Rheumatology (Oxford), 2005, 44: ) Jolly M, Curran JJ: Infliximab-responsive uveitis and vasculitis in a patient with Takayasu arteritis. J Clin Rheumatol, 2005, 11: ) Tanaka F, Kawakami A, Iwanaga N et al: Infliximab is effective for Takayasu arteritis refractory to glucocorticoid and methotrexate. Intern Med, 2006, 45: ) Karageorgaki ZT, Mavragani CP, Papathanasiou MA et al: Infliximab in Takayasu arteritis: a safe alternative? Clin Rheumatol, 2007, 26: ) Santiago MB, Paz O: Rare association of antiphospholipid syndrome and Takayasu arteritis. Clin Rheumatol, 2007, 26: ) Nishimoto N, Nakahara H, Yoshio-Hoshino N et al: Successful treatment of a patient with Takayasu arteritis using a humanized anti-interleukin-6 receptor antibody. Arthritis Rheum, 2008, 58: ) Hoffman GS, Cid MC, Rendt-Zagar KE et al: Infliximab for maintenance of glucocorticosteroid-induced remission of giant cell arteritis: a randomized trial. Ann Intern Med, 2007, 146: Vol. 49, 2009

5 Nobel Strategy for the Treatment of Refractory Vasculitis Syndrome Hidehiro Yamada Division of Rheumatology, Department of Internal Medicine, St. Marianna Medical School, Kanagawa, Japan ANCA-associated vasculitis, Takayasu s arteritis, TNF-α-antagonists, rituximab The recent development of biologic therapies capable of selectively targeting components of the immune system has revolutionized the treatment of inflammatory arthritides. The increase in the use of biologic agents coupled with expansion in the knowledge of the pathogenesis of vascular inflammation has led to their application in the treatment of primary systemic vasculitis. Biological therapies appear to have a place in the therapeutic strategy for ANCA-associated systemic vasculitides, at least for patients whose disease is refractory to conventional therapy. The use of biologics as targeted therapies has also, in reverse, improved our understanding of the pathophysiology of vascular inflammation. However, the precise indications for TNF-alpha inhibitors or anti-cd20 monoclonal antibodies have not yet been defined. These biologics must be prescribed extremely cautiously and only in trial settings, especially in view of the adverse effects. (J Jpn Coll Angiol, 2009, 49: 75 79) Vol. 49, 2009 Online publication June 24,

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