Pro: Perioperative anti-TNF Biologics are safe and do not increase

complications associated with surgery.

Miguel Regueiro, M.D.Professor of MedicineAssociate Chief for EducationClinical Head and Co-Director, IBD CenterUniversity of Pittsburgh School of Medicine

Peyrin-Biroulet L et al. Gut 2011

Probability of using IMM before 1st abd surgery (n=296)

Peyrin-Biroulet L et al. Gut 2011

Probability of receiving at least 1 antiTNF before 1st surgery (296)

This means that most IBD patients undergoing surgery are taking an

IMM and/or antiTNF-If it’s an emergent surgery, we don’t have much choice on altering pre-op meds.

-Should the type of operation be altered?-If the surgery is elective:

-Should we alter pre-op meds?

Is starting an antiTNF in the postop setting safe?

Dr Remzi will argue that peri-operative antiTNF is unsafe

As you may know, there’s a bit of a rivalry between Pittsburgh and

Cleveland

Pittsburgh vs Cleveland

Despite the intercity rivalry, I have the utmost respect for Dr Remzi

and the Cleveland Clinic

In reality, our hospitals and cities are quite similar

UPMC and Pittsburgh on a typical summer morning

Cleveland Clinic on that same, bright summer morning

A Tale of Two Cities – a surgeon’s perspective on postop outcome

• 27 yo CD from Youngstown OH sees Dr Regueiro in Pittsburgh on AZA/ADA

• Develops SBO while in Cleveland and requires emergent surgery w Dr Remzi

• Scenario 1: dc’d 4 days later, “great!” – Dr Remzi – “I am a brilliant surgeon!!”

• Scenario 2: POD 2 develops an anast leak – Dr Remzi – “it’s all because of those poisons Dr Regueiro was giving you!”

Three Scenarios to Consider

• PRE-operative antiTNF for CROHN’S disease and POST-op complications

• PRE-operative antiTNF for ULCERATIVE COLITIS disease and POST-op complications

• POST-operative antiTNF for CROHN’S disease and POST-op complications

PRE-operative antiTNF for CROHN’S disease and POST-op complications

What are the data?

9 Crohn’s ds Postop References• Tay et al. Surgery 2003• Marchal et al. Aliment Pharmacol Ther 2004• Colombel et al. Am J Gastroenterol 2004• Appau et al. J Gastrointest Surg 2008• Indar et al. World J Surg 2009• Canedo et al. Colorectal Dis 2011• Nasir et al. J Gastrointest Surg 2012• Kasparek et al. Inflamm Bowel Dis 2012• Kopylov et al. Inflamm Bowel Dis 2012

Tay – Multivariate analysis suggests improved perioperative outcome in CD

pts receiving IMMs before resection• Overall, 11% Postop complications (5.6%

on IMM, 25% not on IMM)

Marchal – The risk of postop complications associated with IFX for

CD: a controlled cohort study• 12.5% IFX vs 7.7% control: Early

complication Major complications

 Early (within 10 days)

5 (12.5%) IFX 3 (7.7%) No IFX N.S.

Catheter sepsis: 2

Anastomotic leak: 2  N.S.

Anaemia + transfusion: 1

Faecal peritonitis: 1  N.S

Wound infection: 1 Candida sepsis: 1  N.S

Wound failure: 1

Anaemia + transfusion: 1  N.S

Colombel – Early postop complications are not increased in CD treated preop

with IFX or IMM• Overall, 23 % postoperative complications

  N N (%) OR (95% CI)No steroids 193 42 (22) 1.0 (ref)Hi steroids 43 13 (30) 1.6 (0.7–3.3)

No IMM 165 37 (22) 1.0 (ref)

Any IMM 105 26 (25) 1.1 (0.6–2.0)

No IFX 218 51 (23) 1.0 (ref)Any IFX 52 12 (23) 1.0 (0.5–2.0)

Indar – Effect of periop IMM/TNF on early outcome in CD pts

• Overall, 33% postoperative complications

Drug No. of patients No. of complications

None 43 11

Corticosteroids 21 4

IMMs 15 6

Anti-TNFα antibodies 2 1

Canedo – Surgical resection in CD: is IMM associated with higher

postop infxn rates? n(%) IFX (n = 65) ND (n = 75) P value by

complication

Wound infection 9 (13.8) 8 (10.7) P2 = 0.39

Pulmonary infection 1 (1.5) 0 P1 = 0.14

Abscesses 2 (3.0) 2 (2.6) P1 = 0.34

Anastomotic leakage 2 (5.7) 1 (2.43) P1 = 0.39

Reoperations 2 (3.0) 2 (2.6) P1 = 0.2

No infection 49 (75.4) 62 (82.7) P2 = 0.15

Nasir – Periop antiTNF does not increase the early postop complications in CD• Overall, 29% postoperative complications

Abscess/anastomotic leak

N (%) OR (95% CI) OR P valueNo anti-TNF 251 5 (1.99) 1.0 (ref)  Anti-TNF 119 4 (3.36) 1.7 (0.5–6.5) 0.43

Kasparek – IFX does not affect postop complication rates in CD

• Overall, 59% postoperative complications

Major complications

IFX 16 in 13 patients

No IFX 15 in 12 patients p1.0

Anastomotic leak 2 (4%) 6 (13%) 0.27

Intraabdominal abscess 3 (6%) 5 (10%) 0.71

Patients requiring reoperation 11 (23%) 10 (21%) 1.0

Postoperative hospital stay (d) 13 [5–41] 12 [5–54] 0.64

Appau – Use of IFX within 3 mos of IC resection IS associated with postop AEs

..Dr Remzi is co-author...hmmmm……• Overall, 72% postop complications

ComplicationNon IFX group (1998–2007) n = 329 (%)

IFX group n = 60 (%)

Odd’s ratio (95%CI) p-Value

Readmission rate 9.4 20.0 2.40(1.15,5 0.019

Sepsis 9.7 20.0 2.32(1.12, 4.82) 0.024

Intrabdominal abscess 4.3 10.0 2.50(0.92, 6.79) 0.10

Anastomotic leak 4.3 10.0   0.09

Reoperation 3.0 8.3 2.9(0.95,8.81) 0.06

Kopylov – AntiTNF and Postop complications in CD: Systematic

Review and Meta-analysis

- OR 1.7 (CI, .93-3.19) postop complications- Number Needed to Harm = 20

ORs Overall Complications

First Author Type of surgery N Postoperative

complicationsIncreased postop

complications

Tay Segmental

resection with primary anastomosis or strictureplasty

100 11% No

Marchal Intestinal resection (symptomatic stenosis or

refractory fistulas and/orabscesses, or intractable disease)

79 24% No

Colombel Abdominal surgery 270 23% No

Appau ileocolonic resection 389 71.7% Yes

Indar Intestinal surgey (Ileocecal resection and small intestine resection++) 112 33% No

Nasir surgery which included a suture or staple line 370 29% No

Canedo Abdominal surgery 225 ND No

Kasparek Abdominal surgery 96 59% NoKopylov et al. IBD 2012

Risk of postop complications in CD – only one “Yes”

PRE-operative antiTNF for ULCERATIVE COLITIS disease

and POST-op complications

What’s the data?

UC Postop References• Selvasekar et al J Am Coll Surg 2007• Schluender et al Dis Colon Rectum 2007• Mor et al Dis Colon Rectum 2008• Ferrante et al Inflamm Bowel Dis 2009• Norgard et Aliment Pharmacol Ther 2012• Yang et al Aliment Pharmacol Ther 2010UC and CD Studies combined:• Kunitake et al J Gastrointest Surg 2008• Waterman et al Gut 2012

Selvasekar – Effect of IFX on short-term complications in pts undergoins operation for

chronic UC – 62% complicaiton with IFX

Mor – IFX in UC is associated with an increased risk of postop complications

after restorative proctocolectomy

• OR early complication IFX 3.54 (P = 0.004; 95% CI1.51-8.31).

• OR sepsis IFX 13.8 (P = 0.011; 95% CI, 1.82-105)

• OR late complication IFX 2.19 times (P = 0.08; 95% CI, 0.91-5.28)

Norgard – Pre-op use of antiTNF and the risk of postop complications in pts with

UC – a nationwide cohort study• 1226 UC pts – 199 IFX• Most underwent ileostomy (not

IPAA)• OR reoperation 1.07 (95% CI: 0.71-

1.59)• OR anastomosis leakage 0.52 (95%

CI: 0.06-4.11) respectively

Ferrante – Corticosteroids but not IFX increase short-term postop infectious

complications in pts with UC

Yang – Meta-analysis: pre-op IFX + short-term postop complications UC pts

1. short term infxn (NO)

2. short term non infxn (NO)

3. short term overall (YES)

Periop antiTNF UC studiesAuthor Type of

SurgeryN Postoperative

ComplicationsIncreased Postop Complications

Selvasekar IPAA 30147 IFX

62% Yes

Schluender IPAA 13417 IFX

28%37%IFX v 27%

No

Mor IPAA 52385 IFX

OR IFX 3.5 totalOR IFX 13.8 infxn

Yes

Ferrante IPAA 14122 IFX

22% overallSteroids/1 step J

No

Norgard Most Ileostmy

1226199 IFX

OR IFX 0.5 No

Yang Most IPAA

5 studies OR IFX 1.8 Yes

Is starting POST-op antiTNF within 1 mos of CD surgery safe?

Postoperative infliximab is not associated with an increase in adverse

events in Crohn's disease.

Regueiro M, El-Hachem S, Kip K, et al. Dig Dis Sci. 2011 Dec;56(12):3610-5.

No Difference in Adverse Events between Placebo and Infliximab (started within 4 wks of surgery)

Is peri-op antiTNF Safe? Scorecard of Study Results

Timing of antiTNF relative to surgery Yes No

Pre-op CD 8 1

Pre-op UC (includes 2 CD/UC studies)

5 3

Post-op CD 1 0

What I do in practice?

My Practice – periop managementMedication EMERGENT

UC – 3 step IPAA CD – Ostomy, abd sepsis

ELECTIVEUC- 2-3 stepCD- primary anastomosis

Steroids

MTX

6MP/AZA

antiTNF

My Practice – periop managementMedication EMERGENT

UC – 3 step IPAA CD – Ostomy, abd sepsis

ELECTIVEUC- 2-3 stepCD- primary anastomosis

Steroids -Stress dose -Lower to pred <40mg-Taper 24 hr postop (?slow)

-Stress dose -Preop < 20mg Pred -Taper 24hr postop (rapid)

MTX

6MP/AZA

antiTNF

My Practice – periop managementMedication EMERGENT

UC – 3 step IPAA CD – Ostomy, abd sepsis

ELECTIVEUC- 2-3 stepCD- primary anastomosis

Steroids

MTX -Restart at 2wk outpt f/u -Preop no need to stop-Restart at 2wk outpt f/u-Surgeons prefer dc’d >4wks

6MP/AZA -Restart at 2wk outpt f/u -Preop no need to stop-Restart at 2wk outpt f/u-Surgeons prefer dc’d>4 wks

antiTNF

My Practice – periop managementMedication EMERGENT

UC – 3 step IPAA CD – Ostomy, abd sepsis

ELECTIVEUC- 2-3 stepCD- primary anastomosis

Steroids

MTX

6MP/AZA

antiTNF -Preop no choice (emergent) –Restart after 2wk outpt f/u (or when previously scheduled)

-Preop no need to stop-? Dose >6 wks preop (but then chance of flare if delay)-Restart >2wk postop

My Practice – periop managementMedication EMERGENT

UC – 3 step IPAA CD – Ostomy, abd sepsis

ELECTIVEUC- 2-3 stepCD- primary anastomosis

Steroids -Stress dose -Lower to pred <40mg-Taper 24 hr postop (?slow)

-Stress dose -Preop < 20mg Pred -Taper 24hr postop (rapid)

MTX -Restart at 2wk outpt f/u -Preop no need to stop-Restart at 2wk outpt f/u-Surgeons prefer dc’d >4wks

6MP/AZA -Restart at 2wk outpt f/u -Preop no need to stop-Restart at 2wk outpt f/u-Surgeons prefer dc’d>4 wks

antiTNF -Preop no choice (emergent) –Restart after 2wk outpt f/u (or when previously scheduled)

-Preop no need to stop-? Dose >6 wks preop (but then chance of flare if delay)-Restart >2wk postop

Summary Periop antiTNF

• CD: antiTNF is not associated with increased risk when used in the perioperative period

• UC: severity of ds is most associated with complications rather than antiTNF– 3 step IPAA being done anyway

• Practically speaking: surgery should NOT be delayed because a patient is on antiTNF

With that, I give you Dr Remzi