This document discusses inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease. It covers the incidence and symptoms of IBD, diagnostic tests, prognosis, current and emerging treatment options, guidelines for endoscopy and pregnancy in IBD patients. Treatment options discussed include mesalazine, steroids, immunomodulators like azathioprine, biologics/anti-TNF drugs, methotrexate, and nutritional therapy. Side effects of treatments and guidelines for monitoring during pregnancy are also summarized.

1. INFLAMMATORY BOWEL DISEASE
TREATMENT AND PREGNANCY
Dr Theodora Demetriou
MBChB MSc MRCP (UK)
Gastroenterologist / Hepatologist
Paphos General Hospital Cyprus
ECCO Rep. Cyprus
Aliathon
Paphos
21th March 2015

2.  Incidence of Ulcerative colitis and Crohn’s
 Symptoms
 Diagnostic tests
 Prognosis
 Current therapy and side effects
 Emerging therapies
 Survailance endoscopy guidelines
 ECCO pregnancy guidelines
Contents

3.  Ulcerative colitis 150-200/ 100,000 ( 7-22 new cases per
year)
 Crohn’s 50-100/ 100,000 (4-11 new cases per year)
 UK 240.000 IBD patients
 Europe 2 million IBD patients
 Hospital population 300,000: 40- 50 new cases each year
 Incidence is higher in Northern Europe but recently increasing
in Southern Europe
 30% onset before age 18 years old
 Disease activity in children more pronounced and extensive
Incidence of IBD

4. Colon Anatomy

5. Classification of UC
 Involves the mucosa of colon only
 Proctitis- only rectum
 Distal colitis- rectum and sigmoid
 Left sided- descending
 Extensive - transverse
 Pan colitis/ subtotal- right colon
 Adults 80% distal, 42% subtotal
 Children 3% distal, 76% subtotal

6.  90% bloody diarrhoea
 Fatigue, anaemia
 Earlier diagnosis than Crohn’s disease
 Appendicectomy reduction of risk 70%
 3x increase risk in ex-smokers
 29% extra intestinal symptoms that may present
before UC (i.e. Arthritis, Erythema nodosum,
Sclerosing cholangitis, pyoderma gangrenosum,
Uveitis)
Symptoms of UC

7. Extra-intestinal symptoms

8.  Chronic transmural inflammation
 Stricturing
 Fistulating
 Any part of GI tract (stomach, small bowel, colon)
 Ileocaecal valve/ terminal ileum common site
 Not continuous
Classification of Crohn’s disease

9.  stool: normal, diarrhoea, occult blood
 weight loss
 obstruction (distention, vomiting, constipation)
 abdominal pain
 abdominal mass
 fever
 growth failure and puberty delay
 perianal disease (anal fissure, fistula, abscess
 fatigue
 anaemia
Symptoms of Crohn’s disease

10.  Blood tests; full blood count, ferritin, CRP, ESR, liver enzymes
 Stool test: Faecal occult blood test, culture (clostridium difficile,
E.coli, salmonella, campylobacter, CMV)
 Clinical examination of the abdomen
 Anal exam
 Flexible sigmoidoscopy and biopsy
 Colonoscopy- not in acute phase (danger of perforation) and no
preparation
 CT enterography
 MRI small bowel and Pelvis
 Capsule endoscopy
Diagnostic Tests

11. Ulcerative
colitis
Crohn’s disease

12. Capsule endoscopy

13. MRI ENTEROGRAPHY

14.  IPSEN Cohort Norway 1990-1994
 843 IBD (519; UC) patients followed up 1, 5 and 10 years
from diagnosis
 423 UC completed follow up
 No increase in mortality compared to general population
 At 10 years 9.8% colectomy (high risk if ESR>30, Extensive)
 83% relapsing disease
 48% relapse free after 5 years
 20% proctitis progressed to extensive colitis
Prognosis

15. IBD Prognosis IPSEN
55%
1%
6%
37%

16.  Mesalazine/ 5-ASA
 Sulphasalazine
 Azathioprine
 Methotrexate
 Steroids
 Cyclosporine
 Biologics /anti-TNF: REMICADE (infliximab), HUMIRA
(adalimumab)
 Inflectra, Remsima (CT-P13 biosimilar to REMICADE)
 Vedolizumab (anti a4b7)
 Nutritional therapy with semi-elemental diet (MODULEN)
IBD Therapy

17.  MESALAZINE: ASACOL 400 mg tds, SALOFALK 500mg tds,
PENTASA500 mg tds, MEZAVANT1.2g OD
 Sulphasalazine 1gbd
 In acute phase increase 4.5g/day
 Continue long term as reduction in colon cancer risk
 Do not work in small bowel crohn’s
 Mild- moderate UC
 No difference if all take once a day (poor compliance 40%)
 Can use as suppositories and enema proctitis/ sigmoid
 Side effects: nephrotoxic (check renal blood test every 6-12
months)
 Sulphasalazine; nausea, abdominal pain, oligospermia-
reversible
5-ASA

18.  Prednisolone 40mg po/ Medrol po/ Hydrocortisone
(iv)
 Budesonide 9mg/d only in mild to moderate disease
distal ileum/ ascending colon- less side effects
 ECCO guidance: only allow 2 courses of steroids in
one year
 calcium/vit D and omeprazole/ Dexa scan for chronic
steroid users
 Topical steroid less effective than asacol/salofalk
Steroids

19.  Osteoporosis
 Glaucoma/ cataracts
 Cushingoid features
 Acne
 Hypertension
 Gastritis/duodenitis
 Emotional/psychiatric disturbance
 Growth/puberty delay
 Infections/ poor wound healing
Steroid side effects

20.  Slow onset of action (3-6 months)
 Metabolite 6-mercaptopurine (6-MP)
 Remission in 2/3 patients
 Reduction in colectomy and hospitalisation
 Reduction in colorectal cancer risk
Azathioprine

21.  SIDE EFFECTS: 0.3% population no TPMT leads to
more active metabolite BONE MARROW
SUPPRESSION
 2-17% hepatitis
 2% pancreatitis
 Vomiting/nausea (6-MP better)
 Increased risk of Lymphoma (young males also on
Biologics)
 Increase in non-melanoma skin cancers- annual
dermatology review
Azathioprine side effects

22.  Moderate to severe Crohn’s disease
 Not effective in UC (METEOR study 2015)
 25mg IM once a week/ Folic acid 5mg for 4 months
then PO 15mg/wk po
 Effective after 3 months (65% maintain remission)
 Side effects:
1. Contraindicated in pregnancy
2. Hepatotoxicity/ liver fibrosis
3. Bone marrow suppression
Methotrexate

23.  Acute severe colitis
 No difference between infliximab (similar response
and colectomy rates)
 Side effects many so not commonly used any more
 1. hypertension
 2. seizures
 3. Hirsutism
 4. gingival hyperplasia
 5. renal impairment
Cyclosporine

24.  REMICADE/ Infliximab (IV every 2 months for 2hs)
 Adalimumab (sc injection every 2 weeks)
 Moderate to severe ulcerative colitis not responding to
steroids/ steroid dependent/ not responding to AZA
 Reduction in colectomy rate and hospitalisation in
moderate UC (75% 1 yr, 50% 2-3 ys)
 Crohn’s disease with fistulating disease or poor prognosis
(stricturing, deep ulcers, smokers, young age, family
history)
 Remission in 60% and at one year 50%
 Mucosal healing proven to decrease surgery and
hospitalisations
 Better results if given with AZA/ MTX in first 2 years
BIOLOGICS/ ANTI-TNF

25.  Anaphylaxis
 Infusion reactions
 Infections
 Psoriasiform rash
 Exacerbation of MS/ optic neuritis
 Worsening of congestive heart failure
 Increase in non-melanoma skin cancers
 Latent TB reactivation
 Lymphoma risk if given with AZA in young males
 Hepatotoxicity
 Not allowed if untreated TB, hepatitis, malignancy in last 5 years
Side effects of Anti-TNF drugs

26.  Chest x-ray
 Mantoux test
 Hepatitis A,B,C
 CMV/EBV
 Vaccines upto date (annual influenza, 5ys
pneumococcus)
 Varicella/ chicken pox
Before starting anti-TNF

27.  New anti-TNF for UC
 Injection SC once a month
 Fast response at week 6: 52%
 43% mucosal healing
GOLIMUMAB

28.  Antibody to a4b7
 Effective in ulcerative colitis 47%
 Mucosal healing 40%
 Not effective in crohn’s disease
VEDOLIZUMAB

29.  Similar but not identical to original biological medicine
already authorized
 Biological and physiological comparable
 INFLECTRA/ REMSIMA (CT-P13)
 Given like REMICADE 5mg/kg iv every 2 months
 Clinical trials PLANETAS in Ankylosing spondylitis and
PLANETRA in Rheumatoid arthritis.
 Extrapolation of clinical efficiency in IBD by EMA- No
clinical trial exists in IBD
 Small study in Portugal 34 patients 56% responded
33%remission, 9% infusion reactions
 EMA states that country members decide on
interchangeability ( i.e. change REMICADE to Inflectra) but
this decision should be taken by the doctor
BIOSIMILARS

30.  Effective in recurrent C. diff diarrhoea
 No randomised control trial in IBD- only case studies
 Clinical improvement in small study 21 patients (57%)
remission in 14%
 Only for mild UC, no benefit for Crohn’s disease
 No benefit for pouchitis
 Healthy donor faeces given via nasogastric tube or
enema for 3 days
 Safety issues: HIV, Hepatitis A,B,C, Norovirus, CMV,
EBV, Strongyloides, syphilis, parasites
Faecal microbiota transplantation

31.  Increased risk of CRC in IBD if microscopic inflammation
over time
 Mucosal healing in IBD is associated with lower risk of CRC
as well as clinical relapse, hospitalisation and colectomy.
 No increased risk for proctitis
 2.8x risk increase in left sided colitis and Crohn’s colitis
 Family history of CRC and IBD and Primary sclerosing
cholangitis 2-4 x risk increase
 BUT GOOD NEWS:
Measalazine long term 50% reduction in CRC/ dysplasia
Azathioprine decreases risk of CRC in IBD
Colorectal cancer surveillance

32.  Early postoperative recurrence is associated with
higher symptomatic and surgical recurrence rates
 Ileocolonoscopy recommended 6-12 months after
surgery
 Start colonoscopy surveillance 8 years from diagnosis
 Start as soon as PSC diagnosed
 HIGH RISK every year; PSC, Family history CRC<50 or
stricture/dysplasia in last 5 years
 INTERMEDIATE RISK 2-3 years; extensive colitis,
inflammatory polyps, FHCRC >50
 LOW RISK 5 years
ECCO Endoscopy guidelines

33.  FERTILITY: normal in females with IBD (only reduced
slightly if open surgery; colectomy, pouch, ileostomy)
 Laparoscopic pouch/ anal anastomosis lower
infertility
 Acute Crohn’s disease temporary amenorrhea but
associated with weight loss
 Male IBD normal fertility (if pouch abscess/ fistula
disturbance in erection/ejaculation)
 Sulphasalazine temporary infertility 80% - Change to
mesalazine
 Methotrexate contraindicated in men and female IBD
patients trying to conceive
ECCO PREGNANCY GUIDELINES

34.  if conception occurs at time of remission the risk of
relapse during pregnancy is low but high if
conception during active disease
 At second/ third pregnancies less active
disease/surgery risk
 C-section if active perianal disease or active rectal
involvement or Pouch/ Ileo-rectal anastomosis
 After delivery no increased risk of flare if remain on
medication
 Parents with IBD; higher risk of having children with
IBD, Higher if both parent have Crohn’s, transmission
more from mother, female children higher risk
ECCO PREGNANCY GUIDELINES

35.  C- section more common
 Higher risk of low birth weight/ preterm birth – this is
associated with disease activity during pregnancy
 No increase in congenital abnormalities
 Normal APGAR scores
 No increase in ITU admission
 No increase in seizures or death
Pregnancy and Fetal outcomes

36. DRUG PREGNANCY BREASTFEEDING
Mesalazine Low risk Low risk
Sulphasalazine Low risk Low risk
Steroids Low risk Low- delay 4hs before
Azathioprine Low risk Low risk
Anti- TNF ( REMICADE/
HUMIRA)
Low risk- STOP AT 24
WEEKS
Limited data/low risk
Methotrexate NOT ALLOWED NOT ALLOWED
Thalidomide NOT ALLOWED NOT ALLOWED
Metronidazole AVOID 1ST TRIMESTER AVOID
Ciprofloxacin AVOID 1ST TRIMESTER AVOID
IBD medication during pregnancy

37.  DO NOT ignore your symptoms
 Acceptance of disease
 Emotional support
 Medication management
 Disclosure of disease (work/ family/ friends)
 Incontinence
 Fistula care
 Travel
 Support in employment/ university
 Multidisciplinary management (nurse specialist, dietician,
psychologist/ other specialties- rheumatologist)
Promoting self care