Presentation on theme: "Miguel Regueiro, M.D. Professor of Medicine"— Presentation transcript:
1After ileo-colonic resection, how can we prevent or delay the recurrence of Crohn’s disease? Miguel Regueiro, M.D.Professor of MedicineAssociate Chief for EducationClinical Head and Co-Director, IBD CenterUniversity of Pittsburgh School of Medicine
250% - 65% of CD pts still go to surgery: despite earlier and more IMM/antiTNF usage IN 2013:CD treatment relies on initiation of med rx in response to sx’s – in many pts, the tissue damage may be irreversible.
3The Natural Course of postop CD Recurrence is clinically silent initiallyHistologicEndoscopicRadiologicClinicalSurgical30% 3 yr60% 5 yrWithin1 week70-90%by 1 yrTissue damage50% by 5 yrsSurgery D’Haens G, Geboes K, Peeters M, et al. Gastroenterology 1998;114: Olaison G, S medh K, Sjodahl R. Gut 1992;33: Rutgeerts P, Geboes K, Vantrappen G, et al Gastroenterology 1990;99: Sachar DB. Med Clin North Am 1990;74:
4Endoscopic Recurrence Endoscopic Remissioni0: no lesionsi1: < 5 aphthous lesionsi2: > 5 aphthous lesions with normal intervening mucosai3: diffuse aphthous ileitis with diffusely inflamed mucosai4: diffuse inflammation with large ulcers, nodules, and/or narrowingEndoscopic RecurrenceRutgeerts P, Geboes K, Vantrappen G, et al Gastroenterology 1990;99:
5>70% of Pts Have i2,3,4 Recurrence 1 Year after Surgery – Rutgeerts et al Gastro 1990 i0 and i1 remission-low likelihood of progressioni4i,3i2,i3,i4 recurrenceLikely progressionto another surgery
6More Questions than Answers Algorithm for post-op CD managementMore Questions than Answers???5-ASA?Antibiotics?Steroids?6MP/AZA?What about anti-TNFs/Biologics?How should we follow these patients?When to Colonosocope?Are there predictors of disease recurrence?
7Medications for Preventing Postoperative Crohn’s Disease
9Limitation of the studies: the best we can expect are endoscopic recurrence rates of ~45% This means that despite postop meds, nearly half of CD pts will have also have a clinical recurrence and require future surgery
10What about Postop antiTNF? Recently: A lot of discussion and focus on postop antiTNFs – is it worth the hype?
11RCT: Infliximab Prevents Crohn’s Disease Recurrence after Ileal Resection Regueiro M, Schraut W, Baidoo L, Kip KE, Sepulveda AR, Pesci M, Harrison J, Plevy SE.Gastroenterology 2009;136:
12Randomized, two-armed, double-blind, placebo-controlled trial Sample size power calculationAssuming 80.0% recurrence in placebo group, 20.7% recurrence in infliximab group 24 total pts needed (2-sided type I error rate of 0.05)24 patients randomly assigned to infliximab 5mg/kg or placebo within 4 weeks of surgery (0,2,6, and every 8 weeks for one year)
13Infliximab vs placebo p=0.0006 1/1111/13Endoscopic Recurrence defined as endoscopic scores of i2, i3, or i4.
14Are there other postop antiTNF studies? …but this is only one small study, should we really initiate postop antiTNF based on this?Are there other postop antiTNF studies?
15Postop CD: Endoscopic Recurrence antiTNFPlacebo/5ASASorrentino1 (2 yr)(MTX/INF v 5ASA)0%100%Regueiro2 (INF vs PBO RCT 1 yr)9%85%Yoshida3 (INF vs PBO Open 1 yr)21%81%Fernandez-Blanco 4 (ADA 1 yr )10%N/APapamichael5 (ADA 6mos)Savarino6 (ADA 3yr)Aguas7 (ADA 1 yr)21% (high risk pts)Sorrentino et al. Arch Intern Med 2007Papamichael et al. JCrohnsColitis 2012Regueiro et al. Gastroenterol 2009Savarino et al. Europ Journal Gastro Hep 2012Yoshida et al. Inflamm Bowel Ds 2011Aguas et al. World J Gastro 2012Fernandez-Blanco et al. Gastroenterol 2010A
16Why not delay therapy until there is endoscopic recurrence? Insights into mucosal healing in Crohn’s ds – Med Tx trials vs postop prevention vs rx of postop recurrence.
19If Healing the Mucosa is Important – The Mucosal Healing Awards MedalTiming of antiTNFEndoscopic Remission(mucosal healing)
20If Healing the Mucosa is Important – The Mucosal Healing Awards MedalTiming of antiTNFEndoscopic Remission(mucosal healing)BronzeDelay until CD dx(2yrs to many yrs)11% – 44%
21If Healing the Mucosa is Important – The Mucosal Healing Awards MedalTiming of antiTNFEndoscopic Remission(mucosal healing)SilverDelay until endosc recurrence38% - 61%BronzeDelay until CD dx(2yrs to many yrs)11% – 44%
22If Healing the Mucosa is Important – The Mucosal Healing Awards MedalTiming of antiTNFEndoscopic Remission(mucosal healing)GoldImmediately after Surgery90% - 100%SilverDelay until endosc recurrence38% - 61%BronzeDelay until CD dx(2yrs to many yrs)11% – 44%
23Anti-TNF therapy is most effective in early disease 4/10/2017PostopAntiTNFAnti-TNF therapy is most effective in early disease80REACHSUTD60CHARMRemission at 1 year (%)40SONICACCENT I2012345678910Disease duration (years)D’Haens G, et al. Lancet 2008;371:660–67; Hyams et al. Gastroenterology 2007;132(3):863–73; Colombel J-F, N Engl J Med 2010 ;362;1383‒95; Hanauer S, et al. Lancet 2002;359:1541–49; Schreiber S, et al. Gastroenterol 2007;132(4 Suppl 2):A-147; Colombel J-F, et al. Gastroenterology 2007;132:52–65.
24What about long-term postoperative Crohn’s ds? Most studies stop at one year
25Regueiro M, Kip K, Baidoo L, Swoger J, Schraut W. Infliximab Maintenance Prevents Endoscopic and Surgical Crohn’s Disease Recurrence: Long-term Outcomes from the Randomized Controlled Postoperative Prevention StudyRegueiro M, Kip K, Baidoo L, Swoger J, Schraut W.
26Long-term outcomes in patients assigned to placebo or infliximab after surgery 1 yearEnd RCTIFXStatus> 5 yearsAfter SurgeryTime 0SurgeryIFX (11)PBO (13)Figure 1
27Long-term outcomes in patients assigned to placebo or infliximab after surgery 1 yearEnd RCTIFXStatus> 5 yearsAfter SurgeryTime 0No Recurrence*No SurgeryCont. IFX (3)Recurrence (1)Remission (10)SurgeryIFX (11)Recurrence (8)Surgery (5)Stop IFX (8)PBO (13)*1 IFX patient i3 at 1 year after surgery, remained i3 through 6 years+All 5 patients had been i3 or i4 and all progressed to surgery^This pt had been i1 at end of RCT but progressed to i4 and another surgeryFigure 1
28Long-term outcomes in patients assigned to placebo or infliximab after surgery 1 yearEnd RCTIFXStatus> 5 yearsAfter SurgeryTime 0SurgeryIFX (11)Recurrence (5)+Surgery (5)Start IFX (12)Recurrence(11)Remission (2)PBO (13)No IFX (1)Recurrence andSurgery^*1 IFX patient i3 at 1 year after surgery, remained i3 through 6 years+All 5 patients had been i3 or i4 and all progressed to surgery^This pt had been i1 at end of RCT but progressed to i4 and another surgeryFigure 1
29How should we manage a Crohn’s ds pt who recently had surgery? Two practical approaches
30Active cigarette smoking Relative Risk FactorsEarly age of surgery (<30)Short time to first surgeryIleocolonic diseaseActive cigarette smokingProgressed to surgery despite immunomodulatorsPenetrating (fistulizing) diseaseHistory of prior resection
31The POCER approach De Cruz, et al The POCER approach De Cruz, et al. DDW 2013 (POCER = postoperative Crohn’s endoscopic recurrence study)Optimising post-operative Crohn’s disease management: best drug therapy alone versus colonoscopic monitoring with treatment step-upPublication pending
33My Approach – Almost All of my patients start a med after surgery …but NOT necessarily an antiTNF - take into account Risk Factors for Recurrence
34Risk of Post-Op Recurrence LowModerateHighNo Meds6MP or AZA ± metronidazoleAnti-TNFColonoscopy 6-12 months post-opColonoscopy 6-12 months post-opNo RecurrenceRecurrenceNo RecurrenceRecurrenceColonoscopy every 1-3 yrsImmunomodulator or anti-TNFColonoscopy every 1-3 yrs anti-TNF or Δ biologicsPenetrating disease, > 2 surgeries<10yrs CD, long stricture or inflammatory CDLong-standing CD, 1st surgery, short stricture