Advances in the Treatment of Crohn’s Disease GASTROENTEROLOGY 2004;126:1574–1581

INTRODUCTION Crohn’s disease (CD) – –a chronic inflammatory bowel disorder – –transmural, granulomatous inflammation – –involving any part of the GI tract in a discontinuous manner. The peak incidence of CD – –during the adolescent and young adult years

Conventional therapies – –corticosteroids and immunomodulators – –Most children with CD will experience ongoing disease activity – –Side effects : impaired growth, osteoporosis, the risk of hepatitis, bone marrow suppression. – –Approximately 40% of patients require surgical resection. New approaches to the management of pediatric CD are currently needed.

Tumor necrosis factor (TNF) – –targeted proinflammatory cytokine Previous studies in adults – –TNF plays an important role in CD – –The chimeric anti-TNF monoclonal antibody, infliximab – –potent anti-inflammatory agent – –neutralizing its biological activity

The use of infliximab with moderately to severely active CD – –Single infusion of 5 mg/kg – –Beneficial for adults who have an inadequate response to conventional therapy patients with fistulizing disease – –Initial 5mg/kg dose with doses at 2 and 6 wk – –In adults, disease activity decreases after infliximab therapy. – –in a pediatric population, Infliximab may be safe and effective as short-term therapy of medically refractory moderate to severe CD AM J. OF GASTROENTEROLOGY Vol. 98, No. 4, 2003 N Engl J Med 350;9 26, 2004

Pathophysiology type 1 helper T- ell (Th1) cytokines – –TNF-a, interleukin-12, and interferon- γ, – –primary role in initiating the disease process. – –Intestinal epithelium damage

TNF antagonists Infliximab Infliximab a murine human chimeral monoclonal antibody against TNF-a rheumatoid arthritis and Crohn’s disease and ankylosing spondylitis. Etanercept Etanercept a fusion protein that binds free TNF-a rheumatoid arthritis, ankylosing spondylitis, psoriatic arthropathy, and juvenile idiopathic arthritis Adalimumab Adalimumab a recombinant fully humanised mab against TNF rheumatoid arthritis

Treatment (Cecil)

우리나라 보험규정 보건복지부 고시 제 호 보편적인 치료 (2 가지 이상의 약제 ) 에 반응을 나타내지 않는 중등도 또는 중증의 활성 크론병 ( 크론병의 활성도 CDAI 220 이상 ) 및 누공성 크론병에 투여시 용법 용량 범위내 ( 누공이 없을때는 1 회, 누공이 있을때는 3 회 이내 ) 에서 인정함

Crohn’s dis. Activity index (CDAI)

Perianal crohn’s fistula

Tuberculosis and anti-TNF