1. Inflammatory Bowel Disease: Ulcerative Colitis and Crohn’s Disease Update
Dr. Shelley Rahn
October 13, 2017

2. Topics We Will Cover - IBD
Etiology
Similarities and differences
Treatment update
Underwriting concerns
Cases

3. Mucous Colitis –Spastic colitis
What we will not cover
IBS - Irritable Bowel Syndrome

4. Inflammatory bowel diseases Cause mostly not understood
Common Features
Inflammatory bowel diseases
Cause mostly not understood
Genetic predisposition
Autoimmune component
Multifactorial
Symptoms
Gastrointestinal bleeding
Ulceration
Abdominal cramps/pain
Diarrhea
Weight loss
Relapse/remission
Extraintestinal manifestations
Increased cancer risk in affected large intestine after 8-10 years since disease onset
Treatment

5. Extraintestinal manifestations
Improve with improved IBD
Independent of activity of IBD
Arthritis – pauciarticular asymmetric, less than 5 large joints, migratory
Arthritis polyarticular, symmetric, 5 or more small joints
Episcleritis
Ankylosing spondylitis
Sacroiliitis
Aphthous ulcers
Uveitis
Erythema nodosum
Primary sclerosing cholangitis (PSC)
Pyoderma gangrenosum
Bold = more common in UC than Crohn’s, R = more common in Crohn’s

6. Common Laboratory Manifestations
Iron deficiency anemia
Low serum albumin
Elevated sedimentation rate (ESR)
Elevated C reactive protein (CRP)
Fecal calprotectin
Serologic testing – pANCA, ASCA – Prometheus testing

7. Clinical Evaluation – Imaging/Endoscopy
Upper GI series with small bowel follow through
CT scan
CT enterography
MR enterography
Upper endoscopy
Colonoscopy with evaluation of the terminal ileum
Small bowel enteroscopy

8. Celgene.com Microsocpic: Granulomas Microsocpic: No Granulomas
Complications:
Abscesses
Fistulas
Strictures
Complications:
No abscesses
No fistulas
Toxic megacolon
Stricture only if there is cancer
Celgene.com

9. Crohn’s and Ulcerative Colitis Endoscopic Images

10. Crohn’s

11. Ulcerative Colitis Images

12. UC VS Crohn’s
Ulcerative Colitis
Crohn’s

13. Crohn’s vs Ulcerative Colitis
CROHN’S ONLY
ULCERATIVE COLITIS ONLY
Entire GI tract
Colon only
Rectum always
Skip lesions
Continuous – no skip areas
Intestinal narrowing (strictures)
Strictures only if cancer present
Abscess formation
Fistulas (bowel to bowel, skin, or GU tract
Granulomas on micro exam

14. Crohn’s vs Ulcerative Colitis (cont’d)
CROHN’S ONLY
ULCERATIVE COLITIS ONLY
Perianal disease
Rare
Toxic megacolon rare
Toxic megacolon rare but more common than Crohn’s
Surgery not curative
Proctocolectomy curative

15. ULCERATIVE COLITIS

16. Treatment Historical perspective
Crohn’s and Ulcerative Colitis can be chronic, frequently disabling diseases
Relapsing/remitting course
Surgical intervention
Poor quality of life
Often starts in younger ages causing years of low productivity (although there is a second peak onset in older women ages 60-70)
Steroid dependence

17. Treatment
Steroids (immune suppressants) prednisone budesonide
5-ASA preparations – sulfasalazine, mesalamine
Antibiotics – metronidazole, rifaxamin, cipro
Non-Steroidal Immunosuppressants
Non-biologics
Biologics

18. Nonsteroidal immunosuppressants:
Non biologics – oldies, ? goodies
Methotrexate (MTX)
6-mercaptopurine -6MP (Purinethol)
Azathioprine (Imuran)
Cyclosporine, tacrolimus
Biologics – relatively new kids on the block, very effective
Tumor necrosis factor (TNF) inhibitors
Anti - integrins or Integrin inhibitors

19. Biologics TNF inhibitors (Anti TNFs) infliximab (Remicade)
adalimumab (Humira)
certolizumab (Cimzia)
ustekinumab (Stelara)
golimumab (Simponi)
Integrin inhibitors (Anti-integrins)
natalizumab (Tysabri) – rarely causes white matter disease of the brain
vedolizumab (Entyvio) no adverse brain effect – does not cross blood brain barrier
etrolizumab
Add in biosimliars

20. Biologics What makes them biologic?
They are “manufactured” in living cells – yeast, bacteria or human cell lines
They are antibodies
If they work so well, why aren’t they used as first line drug?
Life long commitment thus far
Expensive
Infusion or injected
Side effect profile

21. Biologics are being used more commonly and earlier in disease course
Biologics: What’s New?
Biologics are being used more commonly and earlier in disease course
No longer reserved for severe disease only
Side effect profile better understood and less frightening
Infection risk and possible lymphoma risk – probably similar to non-biologics - small risk, worse if combined with non-biologics and/or steroids
Newer anti integrin – vedoluzimab (Entyvio)-safer

22. Adverse Effects of Biologics
Injection site reactions
Infusion reactions (immediate and delayed)
Joint aches, muscle aches, fatigue, fever
Serious infection
Tuberculosis (screen with PPD)
“Opportunistic infections” (legionella, listeria, fungal)
Activation of Hepatitis B or C
Demyelinating disease? (relationship not established)
Heart failure/pulmonary disease (no clear evidence)
Malignancy

23. Biosimilars – the future
New formulations of biologics
Nearly identical to “reference” or “originator” biologic
Same clinical activity, safety profile, purity
Different inactive components
Theoretically cheaper

24. FDA Approved Biosimilars
Date of Biosimilar FDA Approval
Biosimilar Product
Original Product
March 6, 2015
filgrastim-sndz/Zarxio
filgrastim/Neupogen
April 5, 2016
infliximab-dyyb/Inflectra
infliximab/ Remicade
August 30, 2016
etanercept-szzs/Erelzi
etanercept/Enbrel
September 23, 2016
adalimumab-atto/Amjevita
adalimumab/ Humira
April 21, 2017
infliximab-abda/Renflexis
August 25, 2017
adalimumab-adbm/Cyltezo
September 14, 2017
bevacizumab-awwb/Mvasi
bevacizumab/Avastin

25. Malignancy
The only malignant condition for which a clear relationship has been established is non-melanotic skin cancer

26. Case #1 28 y o female attorney: a)Life - $1 million of term and
b)Disability- $3000/month benefit, 90 day elimination period, to age 65 benefit period, future insurability rider (extra cost to allow additional monthly benefit with financial underwriting only)
On application
Colitis diagnosed 7 years ago
Last visit one year ago
Meds: Imuran, Asacol (mesalamine preparation – 5- ASA)

27. What do you want to know? What disease does she have? Crohn's or UC
What has been the clinical course?
If Crohn’s:
Other parts of GI tract involved
Abscess, fistula, surgery
Perianal disease

28. What do you want to know? (cont’d)
If either Crohn’s or UC:
Degree of severity with flares weight loss, bleeding, anemia
Responsiveness to treatment
Specific medications
Extraintestinal manifestations – joints, back, skin, biliary disease
Degree of adequate follow up – most recent colonoscopy
History of surgery and type of surgery
Current labs – albumin, liver enzymes

29. Underwriting considerations - UC
Favorable
Disease stability
Sulfasalazine or other 5 ASA medication or no treatment
Disease limited to proctitis
Routine colonoscopy for disease ≥8-10 years
Currently asymptomatic
Symptoms mild with flares
Normal LFTs especially alkaline phosphatase– no sclerosing cholangitis
No extracolonic symptoms
No current anemia (when data available)
Normal serum albumin (when data available)
No dysplasia or colon cancer

30. Underwriting considerations - UC
Unfavorable
Recent diagnosis (within past 6 months to a year)
Immunosuppressant medications
Disease beyond the rectum
Inadequate surveillance colonoscopy
Current symptoms
Severe symptoms with disease flares
Abnormal LFTs- particularly Alk phos and GGT
Extracolonic symptoms
Current anemia Hgb ≤ 10.5 (when data available)
Serum albumin <3.8 (when data available)
Dysplasia or colon cancer
Add in dysplastic associated mass lesions

31. Crohn’s Disease UW Considerations Favorable
Diagnosis older than age 25
Mild symptoms
BMI ≥ 18
No anemia
Serum albumin ≥
No surgery
No prolonged steroid use
No immunosuppressant use
Diagnosis more than 3-5 years ago
Mild or no extra-intestinal manifestations
Adequate follow up

32. Underwriting Considerations – Crohn’s
Unfavorable
Moderate to severe symptoms
BMI <18
Anemia
Serum albumin <
Immunosuppressant other than occasional steroids or methotrexate
History of surgery, abscess, stricture, fistula
Diagnosis less than 5 years ago
Inadequate follow up

33. APS information
Crohn’s colitis and terminal ileitis diagnosed 9 years ago – abdominal cramps, bloody diarrhea. Not hospitalized
Diagnosed by colonoscopy with skip lesions, terminal ileum involvement, granulomas on biopsy
No extraintestinal manifestations
Initially treated with prednisone and mesalamine
Improved but relapsed whenever prednisone was tapered
Started Imuran about 7 years ago and has been stable since
Current labs normal
BMI 22 - stable
No history of surgery
Last colonoscopy 7 years ago

35. Severity of disease/Mortality and Morbidity Risk
Mild, Moderate or Severe
Flares easily controlled but requires immunosuppressant therapy
Otherwise stable
Moderate Crohn’s (not the same as mortality risk)
Assess based on mortality/morbidity associated with
Underlying disease – risk of progression, complications including colon cancer
Treatment – risk of medications – infection, malignancy

36. Mortality Risk Mortality risk has been studied in populations –
Some studies indicate similar to population (not the same as an insured population)
Other studies find 50% increase mortality over standard population
So how do we assess mortality
Have to assess on an individual basis as those with complications have a higher mortality
Poorly responsive to medication, fistulas, abscesses, multiple surgeries, recurrent infections

37. “What ifs?”
What if she was 11 years since diagnosis with no colonoscopy in 5 years?
risk of colorectal cancer increases by 0.5-1% per year.
What if she had a recent colonoscopy with finding of pseudopolyps?
What if she had a recent colonoscopy with low grade dysplasia?
Incidence of cancer is 2-3/100 person years
What if her labs showed alkaline phosphatase of 210/GGT 150?

38. What if she was a trial attorney?
Beware of stress related comments in the APS
Be aware of occupation limiting access to bathroom facility

39. Case #2 28 y o female attorney: a)Life - $1 million of term and
b)Disability- $3000/month benefit, 90 day elimination period, to age 65 benefit period, future insurability rider (extra cost to allow additional monthly benefit with financial underwriting only)
On application
Crohn’s colitis diagnosed 7 years ago
Last visit one year ago
Meds: Remicade (infliximab), Asacol (mesalamine preparation – 5-ASA)
Does this alter risk assessment?

40. Case #3 - What if she was not on immunosuppressants?
28 y o female attorney:
a)Life - $1 million of term and
b)Disability- $3000/month benefit, 90 day elimination period, to age 65 benefit period, future insurability rider (extra cost to allow additional monthly benefit with financial underwriting only)
On application
Crohn’s colitis diagnosed 7 years ago
Last visit one year ago
Meds: Asacol (mesalamine preparation – 5-ASA)
Does this alter risk assessment?

41. What if she told us on the application that she had colitis since 2001, on dicyclomine?
Need to determine if this is IBD or IBS (inflammatory bowel disease or irritable bowel syndrome)
Dicyclomine (Bentyl) - not usually for IBD, mostly used for IBS

42. Summary Complicated diseases with many factors to consider
Mortality risk – devil is in the details – can be low to uninsurable
Morbidity risk – can truly be disabling but motivation, occupation can play a major role
Biologics have been miracle drugs and have changed the course of the disease
More drugs surely to come
Better screening for colon cancer risk will come eventually

43. Questions