William J. Sandborn, M.D., Brian G. Feagan, M.D., Paul Rutgeerts, M.D., Ph.D., Stephen Hanauer, M.D., Jean-Frederic Colombel, M.D., Bruce E. Sands, M.D., Milan Lukas, M.D., Ph.D., Richard N. Fedorak, M.D., Scott Lee, M.D. Vedolizumab as Induction and Maintenance Therapy for Crohn’s Disease 수요저널 R1. 박은지 / Pf. 이창균 T h e new engl and journa l o f medicine 369;8, august 22, 2013

Introduction Crohn’s disease (CD) ; Chronic inflammatory bowel disease 1) Glucocorticoids 2) Immunosuppressive agents Azathioprine, mercaptopurine, methotrexate 3) TNF antagonists → Many patients do not have a response to therapy !! → Toxic effects !! → Monoclonal Ab

Introduction Natalizumab ; Monoclonal Ab → modulates gut and brain multiple sclerosis, Crohn’s disease (BUT) Progressive multifocal leukoencephalopathy (PML), Brain infection Vedolizumab ; humanized Ig G1 monoclonal Ab → modulates gut (not Brain!!) Induction & maintenance trials of vedolizumab in patients with moderately to severely active Crohn’s disease ~!

- Randomized, parallel-group, double-blind, placebo-controlled study - Induction and maintenance trials ~ medical centers in 39 countries - No response or unacceptable side effects ; glucocorticoids, immunosuppressive agents, TNF antagonists Methods (1) InclusionExclusion 18~80 ages at least 3 months CDAI 220~450 1 of 3 - CRP > Coloscopy; Large ulcer > 3 - Aphthous ulcer > 10 - Fecal calprotectin concent > 250 μg/g (+evidence of ulcers) ; CT, MR, capsule endoscopy Adalimumab within 30 days Infliximab within 60 days Certolizumab pegol within 60 days Stoma Small-bowel resections (>3) Short-bowel syndrome Extensive colonic resection Intestinal stricture Abdominal abscess Active or latent Tb Cancer

End-Point measures → Induction trial N=368; vedolizumab : placebo (cohort 1) Maintenance trial N=747; open label vedolizumab (cohort 2) → Integration of induction trial & maintenance trial Methods (2) Induction trial (f/u at week 6)Maintenance trial (f/u at week 52) Primary end-point (2) 1)Remission ; CDAI < 150 2)Response ; CDAI > 100 decrease Secondary end-point 1) CRP change (from baseline) Primary end-point (1) 1) Remission ; CDAI < 150 Secondary end-point 1) Response ; CDAI > 100 decrease (without glucocorticoid ) 2) Durable remission

Methods (3)

Results (1) Figure 1. Primary End Points in the Trial of Induction Therapy Primary end pointSecondary end point

Results (2) Figure 2. End Points in the Trial of Maintenance Therapy

Results (3) Figure 3. Primary End Points in the Trial of Maintenance Therapy Primary end point Secondary end point

Results (4)

Conclusion Vedolizumab were more likely than placebo to have a Remission Not CDAI-100, at week 6 !! (only induction) → continued vedolizumab → Response at week 52 (maintenance) Adverse events were more common with vedolizumab

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