1. IBD: A Comorbidity of PSC
Laura Raffals, MD, MS

2. The Spectrum of IBD 1.6 Million Americans
ULCERATIVE COLITIS
Continuous inflammation
Colon only
Superficial inflammation
Variable involvement
Risk of cancer
Strictures (cancer)
Extraintestinal manifestations
CROHN’S DISEASE
Patchy inflammation
Mouth to anus involvement
Full-thickness inflammation
Variable involvement
Fistulas
Strictures
Extraintestinal manifestations
Indeterminate colitis 10-15%

3. Temporal Trend in the Incidence of Crohn’s Disease in Olmsted County, 1940-2004
This graph shows the temporal trend in the incidence of Crohn’s disease in Olmsted County for the period
In the 1940s the incidence rate for Crohn’s disease was low. During the 1950s and 60s the incidence rate rose sharply, but since the early 1970s the incidence rate has remained relatively stable.
Ingle SB, et al. Gastroenterology 2007 Suppl

4. Temporal Trend in the Incidence of Ulcerative Colitis in Olmsted County, 1940-2004
A similar trend is seen for ulcerative colitis.
Again, in the 1940s the incidence rate is low, climbs sharply in the 1950s and 1960s, and has remained stable since the 1970s.
Ingle SB, et al. Gastroenterology 2007 Suppl

5. Changing Geographic Distribution of IBD
1950
2000 5

6. Genetic susceptibility Environmental triggers
Pathogenesis of IBD
Immune
Response
Genetic susceptibility
Environmental triggers
IBD CP

7. Disease Extent Crohn’s can involve any part of GI track
But colon alone in 20-30%
UC involves only the colon
But “backwash ileitis” in 7-15%
PSC-IBD
Is this its own entity?

8. Anatomic Distribution of CD
Upper gut < 10%
Small bowel alone 33%
Ileocolonic 45%
Colon alone 20%

9. CD: Clinical Patterns
Fibrostenotic
Inflammatory
Fistulizing

10. CD: Clinical Patterns
Fistulae
and
Abscesses

11. Anatomic Extent of UC Left-Sided Colitis Pancolitis Procto-
sigmoiditis

12. PSC-IBD

13. PSC & IBD 70% of PSC patients have IBD 80% UC 10% CD 10% Indeterminate
5% of IBD patients have PSC
All IBD patients should have liver enzymes tested annually

14. PSC-IBD PSC-IBD is a unique entity Relatively quiescent disease
Increased risk for colorectal cancer
IBD usually precedes PSC diagnosis (median 10 years)
PSC can develop after colectomy

15. PSC-IBD CharacteristicsUC
Pancolitis
Rectal sparing and backwash ileitis
Right side > left side CD
Often ileocolonic
Isolated small bowel disease is rare
Fibrostenotic and penetrating complications are rare
Are these often mischaracterized PSC-IBD patients?

16. PSC-IBD Relationship between colectomy and PSC
Early colectomy is associated with decreased risk for future liver transplantation
Colectomy prior to liver transplant associated with lower risk for recurrent PSC
IBD disease activity NOT associated with risk of recurrent PSC after liver transplant

17. What is the link between IBD & PSC
We don’t know
Bile acids
“Leaky gut”
Gut dysbiosis
Lymphocyte homing
Genetics

18. Risk of colorectal cancer in PSC
Risk of CRC is higher in IBD compared to general population
Patients with PSC-IBD at greater risk of CRC compared to IBD alone
Pancolitis and inflammation are additional risk factors for CRC

19. CRC screening guidelines
Colonoscopy should be done in all patients at time of PSC diagnosis if no history of IBD
If no colitis, continue colonoscopies every 3- 5 years
In patients with PSC-IBD, annual colonoscopy
Chromoendoscopy
Colectomy is recommended if CRC or high grade dysplasia

20. IBD Treatment

21. Treatment goals in IBD in 2019 are rapidly evolving
Cure
Mucosal
Healing
Reduction in
Hospitalizations
and Surgeries
Maintenance of
Steroid-Free Remission
Induction of Remission
Alleviate Symptoms
Changing The Natural
History of Disease?

22. Improved Clinical Outcomes Have Coincided With The Expanding IBD Therapeutic Armamentarium
Re-format
Danese S, Vuitton L, Peyrin-Biroulet L. Nat Rev Gastroenterol Hepatol 2015;12:537-45

23. Treatment categories Therapy 5-ASA Immunomodulators Anti-TNF
Mesalamine (oral & topical)
Sulfasalazine
Immunomodulators
Thiopurines
Methotrexate
Anti-TNF
Infliximab
Adalimumab
Certolizumab
Golimumab
Anti-Integrins
Vedolizumab
Natalizumab
Anti-IL23
Ustekinumab
Small molecules
Tofacitinib

24. Better Treatment Strategies Are Essential for Improving Clinical Outcomes
1. Early intervention

25. The Window of Opportunity for Early Intervention in IBD
Stricture
Surgery
Intestinal damage
Disability
Fistula/abscess
Inflammatory activity (CDAI, CDEIS, CRP)
Stricture
Window of opportunity?
Kara showed us this slide outlining the natural history of CD and the risk of developing complications from disease.
Disease onset
Diagnosis
Early disease
CDAI, Crohn's disease activity index; CDEIS, Crohn’s disease endoscopic index of severity; CRP, C-reactive protein
Pariente B, et al. Inflamm Bowel Dis 2011;17:1415–22

26. Inflammatory activity (CDAI, CDEIS, CRP)
New Treatment Goals - Blocking Disease Progression and Preventing Damage and Disability
Intestinal damage
Disability
Inflammatory activity (CDAI, CDEIS, CRP)
10.04 so this er concept…………with arthritis 10.41
Disease onset
Diagnosis
Early disease
CDAI, Crohn's disease activity index; CDEIS, Crohn’s disease endoscopic index of severity; CRP, C-reactive protein
Pariente B, et al. Inflamm Bowel Dis 2011;17:1415–22 26 26 26 26 26

27. Better Treatment Strategies Are Essential for Improving Clinical Outcomes
1. Early intervention
2. Individualized treatment

28. Predicting the course of disease:
Treatment goals individualized based on disease activity & severity, patient goals and risks
We can’t undo the past
We can impact the future
Defining the likely course of disease
Disease activity: How is the patient now? PROs & objective markers
Disease severity: What has been the patient’s disease course?
Crohn’s disease and ulcerative colitis are heterogeneous diseases, and each aspect of the T2T strategy may need to be tailored to the individual patient. For example, outcomes in late-stage disease will differ from those achievable in early disease. The choice of treatment target may also vary, given that a stringent target may not be achievable in some patient types. For example, symptomatic remission may not be achievable in late-stage disease, and mucosal healing may also be harder to achieve in longstanding disease where there is considerable accumulated bowel damage.
Individual PRO goals should also be considered, and the frequency of PRO outcome assessments tailored to the patient’s symptoms (for example, a minimum every 3 months until symptom resolution and at least every 6-12 months after resolution).
Treatment choices will be tailored to the patient’s prognosis and disease type, and to the risk of treatment toxicity. The frequency and choice of monitoring assessments may also vary by patient.

29. New Paradigm: Treating beyond symptoms
Biologic therapy
Immunomodulators
Corticosteroids
Biologic therapy
Immunomodulators
Corticosteroids, 5-ASA therapies
Symptom severity
Step-up approach
Top-down approach

30. Better Treatment Strategies Are Essential for Improving Clinical Outcomes
1. Early intervention
2. Individualized treatment
4. Tight control monitoring
3. Treat to target

31. Evolving goals of therapy for IBD: sustained deep remission
Clinical parameters
Outcomes
Response
Improved symptoms
Improved QoL
No symptoms
Decreased hospitalization
Remission
Normal labs
Dr Remo Panaccione presented this theoretical model during an Abbott symposium at the ECCO 2010 meeting.
The goals of Crohn’s disease management – together with the corresponding clinical parameters and outcomes – have evolved.
Dr Panaccione suggested that we may be able to sustain these outcomes, and proposed sustained deep remission as potential new treatment goal.
Normal endoscopy
Avoidance of surgery
Deep remission
Mucosal healing
Minimal/no disability
SUSTAINED DISEASE CONTROL
David T. Rubin, MD 2014 31 31

32. Therapeutic Decision Making in IBD is Individualized in Every Patient
RISKS OF UNDER-
TREATMENT
RISKS OF OVER-
TREATMENT
Corticosteroid exposure
Complications - Fibrostenosis / Penetrating
Hospitalizations and surgeries
Colorectal cancer
Disability / Absenteeism
Reduced QOL
Infections
Lymphoma
Other rare AEs
Cost

33. Balancing Risk of Disease & Risk of Treatment

34. Putting risk in perspective
Over a lifetime, the risk of dying from:
Lightning
1 out of 164,968
Bicycling accident
1 out of 4,535
Drowning
1 out of 1,113
Riding in a car
1 out of 470
Cancer
1 out of 7
Heart disease
Odds of Dying, National Safety Council. Available at: Accessed 2015.

35. Risk of Developing non-Hodgkin’s Lymphoma
Patient receiving Immunomodulator +/- anti-TNF Therapy for 1 year
Risk without medication
Risk of lymphoma with immune suppression
Siegel CA, Inflamm Bowel Dis 2010;16:2168.

36. Preventive Care
IBD patients do not receive preventive services at same rate as general medical patients
IBD patients on immunomodulators or biologics have unique needs
Vaccinations
Screening for osteoporosis
Cervical cancer
Skin cancer
Depression/anxiety
Smoking cessation
Health maintenance issues need to be co-managed by PCP and gastroenterologist
Farraye F, et al. American Journal of Gastroenterology. 112(2):241–258, FEB 2017

37. Inactive vaccine recommendations
Infectious agent
Target population
Dosing
Corynebacterium diphtheria, Clostridium tetani, Bordetella pertussis
All
Booster every 10 years
Hepatitis B
If low or absent titer, revaccinate at 1, 1-2, and 4-6 months
HPV
Ages 11-26
Doses at 0, 2, 6 months
Influenza
Annual, inactivated
Neisseria meningitidis
High risk adults
2-3 doses depending on vaccine
Streptococcus pneumonia
PCV13 followed by PPSV23 after 2-12 months
Farraye F, et al. American Journal of Gastroenterology. 112(2):241–258, FEB 2017

38. Multidisciplinary approach – the best care for all
Behavioral health
Radiology & Pathology
Primary care
Specialists
IBD center
Surgeons
Hepatologists
Quinn et al. “Impact of a Multidisciplinary eBoard for Management of Complex IBD”, presented at Crohn’s Colitis Congress 2019

39. Questions & Discussion raffals.laura@mayo.edu