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Inflammatory Bowel Disease in the Primary Care Setting
Lisbeth Selby, MDAssistant professorU i it f K t kUniversity of KentuckyDepartment of Internal MedicineDivision of Digestive Diseases and Nutrition
Outline
• Define IBD
D ib 2 i
• Treatment issues
i• Describe 2 main types – clinical features, course
• Issues common to both
• prognosis
• Diagnostic issues
• Supplementary material– genetics
– reproductive issues
2
Inflammatory Bowel Diseases (IBDs)
Ulcerative Colitis (UC) Crohn’s Disease (CD)
INFLAMMATORY BOWEL DISEASE
Transmural Inflammation
UpperGastrointestinal
ColonicSmall Bowel
Mucosal Ulceration in Colon
Proctitis Left-sided Colitis
Extensive Colitis
Anorectal
Stenson WF, et al. Inflammatory bowel disease. In: Yamada T et al., eds. Textbook of GastroenterologyPhiladelphia, PA: Lippincott Williams & Wilkins;4th Ed. 2003:1699.
Features Supportive of CD vs. UC
• involvement of the small bowel
• sparing of the rectum
• absence of gross bleeding
• presence of bothersome perianal disease
• focality of gross and microscopic lesions
• presence of granulomas
• occurrence of fistulae
3
• Diarrhea, typically bloody and with mucus
Abd i l i d t d
Clinical Presentation of Ulcerative Colitis
• Abdominal pain and tenderness
• Loss of appetite and weight
• Fever
• Fatigue
• Urgency for bowel movement• Urgency for bowel movement
• Urinary symptoms
• Children: growth and developmental failure
Jewell DP. Ulcerative Colitis. In: Feldman M, Friedman LS, Sleisenger MH, eds. Sleisenger & Fordtran’s Gastrointestinal and Liver Disease. Philadelphia, PA: Saunders; 7th ed. 2002:2039.
www.CCFA.org. Accessed July 29, 2005.
4
UC: Natural HistoryUC: Natural History
100
Disease Severity at Presentation
Severe Activity (9%)
40
60
80
ien
ts w
ith
UC
(%
)
Moderate Activity(71%)
(9%)Mild Activity: < 4 stools daily
No systemic disturbanceESR: Nl
Moderate Activity: > 4 stools dailyMinimal systemic effects
Severe Activity: > 6 stools dailyBloody stoolsFever
0
20
Disease Activity
Pat
i
Mild Activity (20%)
FeverTachycardiaAnemiaESR > 30 mm/hr
Hendriksen C, Kreiner S, Binder V. Gut 1985;26:158-163
Disease Course in Ulcerative Colitis
• Severity and extent of UC affect likelihood and timing of colectomy
Cumulative resection rate inversely proportional to age
Clinical Course of UC Patients (n) %
Acute fulminating 20 8.0
Chronic intermittent 161 64.4
Chronic continuous 18 7.2
One attack only 45 18.0
Total colectomy in first attack 2 0 8
• Cumulative resection rate inversely proportional to age
Total colectomy in first attack 2 0.8
Died in first attack of other causes 1 04
Unknown 2 0.8
Total 249 100.00
Edwards FC, et al. Gut. 1963;4;299.Sinclair TS, et al. Gastroenterology. 1983;85:1.
5
Ulcerative Colitis: Defining Extent of Disease
Ulcerative proctitis(rectum only)
Ulcerative proctitis(rectum only)
Left-sided Colitis(extends to splenic
flexure)
Left-sided Colitis(extends to splenic
flexure)
Extensive Colitis(beyond splenic
flexure)
Extensive Colitis(beyond splenic
flexure)
Adapted from Orangio GR. Surgical Therapy for IBD. In: Stein SH, Rood RP, eds. Inflammatory Bowel Disease. Philadelphia, PA: Lippincott-Raven; 1999:155(Fig 10).
www.CCFA.org. Accessed July 29, 2005.
Referral Population Cohort:Referral Population Cohort:Disease Distribution at Disease Distribution at
PresentationPresentationnn== 11161116
37%37%
17%17%
46%46%
17%17%
Farmer RG, Easley KA, Ranking GB. Dig Dis Sci 1993;38(6):1137-1146
6
Natural Course of Ulcerative ColitisNatural Course of Ulcerative Colitis
Proctitis Left-Sided Pan-colitisProctitis Left-Sided Pan-colitis
Progression
Surgery
Regression
Langholz E et al.Scand J Gastroenterol. 1996;31:260-266.Based on a multivariate analysis.
Mild
Endoscopic Severity Index for Ulcerative Colitis
Moderate SevereMild Moderate Severe
• Granular mucosa
• Edematous
• Loss of normal vascular pattern
Images courtesy of R. Cohen MD.Modified from Sutherland LR, et al. Gastroenterology. 1987;92:1894.
• Coarsely granular
• Small ulcerations
• Friable
• Frank ulcerations
• Spontaneous hemorrhage
7
Natural History of Ulcerative Colitis
• Timeline same as Crohn’s
• Depends on where the colitis is located –more towards the end is usually better
• < age 20 or > age 70 may have more trouble
After 15 25 yrs of disease 30% have had• After 15-25 yrs of disease, 30% have had colon removed
Colectomy in Ulcerative Colitis Colectomy in Ulcerative Colitis
100 Cumulative probability for colectomy atCumulative probability for colectomy at
20
40
60
80
Co
lect
om
y %
Co
lect
om
y %
Cumulative probability for colectomy atinitial diagnosis of UC
Cumulative probability for colectomy atinitial diagnosis of UC
PancolitisPancolitis
Substantial ColitisSubstantial Colitis
Winther KV. Clin Gastroenterol Hepatol. 2004;2:1088.Winther KV. Clin Gastroenterol Hepatol. 2004;2:1088.
0
20
0 5 10 15 20 25 30 35
CC
Years of follow-up after UC diagnosis
ProctitisProctitis
8
• ADULT
Clinical Presentationof Crohn’s Disease
• PEDIATRIC– Similar presentation
– Growth and development issues less apparent
– Often had silent disease as child/teen
– Abdominal pain
– Diarrhea
– Weight loss
– Anorexia
– Vomiting
– Rectal bleedingg
– Stunted growth
– Fevers
Dassopoulos T, et al. Presentation and diagnosis of inflammatory bowel disease. In: Cohen RD, ed. Inflammatory Bowel Disease: Diagnosis and Therapeutics. 2003,
Humana Press Inc, Totowa, NJ.Peck SN, et al. Inflammatory Bowel Disease in children and adolescents.
In: Stein SH, Rood RP, eds. Inflammatory Bowel Disease. Philadelphia, PA: Lippincott-Raven;1999:25.
Endoscopic Appearance of Crohn’s Colitis
Normal Mild Colitis Severe ColitisNormal Mild Colitis Severe Colitis
• Loss of normalvascular pattern
• edema
• Deep, linear, “bear-claw”ulcers
Images courtesy of R. Cohen, MD.
9
Locations in the GI Tract Most Often
Affected by Crohn’s Disease
60 sm/lg bowel
10
20
30
40
50
60
~50%
30%20%-25%
Occ
urr
ence
(%
) small bowelcolon
0
10
Small intestine Large intestine Small and large intestine
O
Sands BE. Crohn’s Disease. In: Feldman M, Friedman LS, Sleisenger MH, eds.Sleisenger & Fordtran’s Gastrointestinal and Liver Disease.
Philadelphia, PA: Saunders; 7th ed. 2002:2010.
10
Natural History of Crohn’s Disease
• Intermittent problems w/periods of well b ibeing
• 10-20% may have prolonged remission
• Probably does not change lifespan drastically
Majority of patients need surgery at some• Majority of patients need surgery at some point
• Certain patterns associated w/more severe CD
2
Natural Course of CDNatural Course of CD
Background Information
Postoperative
g
• 5%–20% recurrence rate per year (definition?)
• 73%–93% reappearance of endoscopic lesionswithin 1 year after surgery
• 34%–86% subsequent clinical relapse within 3 years
• No controlled data showing that any surgicalmaneuver decreases recurrence
11
Complications of Complications of
IBD Related Complications
• Severe inflammation• Perforation• Megacolon• Extraintestinal disorders
Co p cat o s oUlcerative Colitis
pCrohn’s Disease
• Fistulas• Abscesses• Intestinal blockage• Extraintestinal disorders
• Colon or rectal cancer• Malnutrition• Colon or rectal cancer• Growth failure in children
Stenson WF, et al. Inflammatory bowel disease. In: Yamada T et al., eds. Textbook of Gastroenterology Philadelphia, PA: Lippincott Williams & Wilkins;4th Ed. 2003:1699.
Extraintestinal Manifestations of IBD
• Peripheral arthritis
– Arthralgia more prevalent in subjects with CD g p j
• Axial arthritis
– Ankylosing spondylitis more prevalent in subjects with UC
• Osteoporosis
– Risk is greater in subjects with CD
• Renal
• Dermatological
Miller MM. Prim Care. 1984;11:271.Stenson WF, et al. Inflammatory bowel disease. In: Yamada T et al., eds.
Textbook of Gastroenterology Philadelphia, PA: Lippincott Williams & Wilkins;4th Ed. 2003:1699.
Dermatological
• Eye
• Thromboembolic
• Hepatic complications
12
Ulcerative Colitis and Increased Risk of Colorectal Cancer
%) 2525
mu
lati
ve p
rob
abili
ty (
%
UCUC
2020
1515
1010
55
Eaden JA, et al. Gut. 2001;48:526.
Cu
m
Time from diagnosis (years)
UCUC55
11
00 55 1010 1515 2020 2525 3030
• Overall prevalence of CRC in any UC patient is 3.7%• Pancolitis > more limited forms
B12
• Crohn’s disease patients with ileali l t il l ti iinvolvement or ileal resection require lifelong parenteral B12 (usually monthly)
• Levels not reliable to determine need either early on or during parenteral therapy
• Very small minority of CD pts have had• Very small minority of CD pts have had gastric resections– They also require B12
13
Folic Acid(Also Called Folate)• Anemia can develop with low body amounts
• All women who could possibly get pregnantAll women who could possibly get pregnant should take 400 micrograms of folic acid every day in a vitamin or in foods that have been enriched with it
• Helps prevent neural tube defects (ex., spinabifida)b da)
• Sulfasalazine patients often recommended folate1 mg day
• Methotrexate patients usually recommended to take folic acid at a dose of 1 mg/day
General Goals of Therapy for IBD
• Inducing remission
• Maintaining remission
• Restoring and maintaining nutrition
• Maintaining patient’s quality of life
• Surgical intervention (selection of optimal time for surgery)
14
What Detemines Choice of Therapy?Some important factors …
• CD vs. UC vs. indeterminate• Disease locationDisease location• Disease severity• Disease behavior
– perforating, strictures• Age of patient• Other medical conditions• Patient preferences & abilities• Availability of treatments
– usually refers to surgery• Reproductive issues
Categories of Medications
• Sulfasalazine
• 5-aminosalicylates
• Antibiotics
• Corticosteroids (i.e., steroids)
• Other immunomodulators
• Biologics
15
Sulfasalazine
• 1 of the older medications
• Most useful for colon disease
• Several wks to full effect
• Allergic reactions; sulfa
• High doses headache
• Folic acid supplements needed
• Less expensive
5- aminosalicylates(5-ASA or mesalamine)
• Multiple forms
• Idea get medicine to where the disease is
• Oral and rectal
• 2 different pill typesA l® & P t ®– Asacol® & Pentasa®
• 2 different rectal medications– Enema & suppositories
16
Common side effects of 5-ASA
• Headache
Abd i
• Dizziness
U i di l ti• Abd pain
• N/V
• Weakness or fatigue
• Belching
• Diarrhea
• Urine discoloration
• Indigestion
Rare Side Effects of 5-ASA
• Bone marrow suppression
• Pericarditis
• Pancreatitis
• Severe allergic symtpoms
• Bloody diarrhea
17
Antibiotics
• Most commonly used®– Metronidazole (Flagyl®)
– Ciprofloxacin (Cipro®)
• Crohn’s vs. UC
• Used especially for perianal fistulae
Metronidazole Side Effects
• Metallic taste
• Nausea
• Nerve damage
• Reaction to alcoholic beverages
18
Common CiprofloxacinSide Effects
• Diarrhea
• Allergic reactions
• Headache
• Dizziness
• PhotosensitivityPhotosensitivity
Rare Side Effectsof Ciprofloxacin
• ?? Joint damage in children• ?? Joint damage in children
• Tendonitis (inflammation of tendons)
• Hepatitis (liver irritation)
• Delirium
19
Steroids
• Used to get rapid control of disease
• Try to avoid for long-term
• Many side effects
• Works by suppressing the immune system
Other Immunomodulators (IM)
• Steroids are IM’s, too
• “Other” = non-steroid
• Usually second line
• 3-6 mos for effect
• More used in maintenance phase since onset slow
• Need for monitoring
20
Examples of Immunomodulators
• Azathioprine (Imuran®)
• 6-MP
• Methotrexate (MTX)
Common Side Effects of Azathioprine, 6-mercaptopurine and Methotrexate
• Bone marrow suppressionpp
• Hepatitis
• Pancreatitis (Azathioprine/6-MP)
• Slight increased risk of cancer long-term
• Methotrexate is a teratogen (category X)Methotrexate is a teratogen (category X)
21
Incidence of Azathioprine/6-MP Side Effects
• Allergic reactionsHigh fever and/or rash and arthritis– High fever and/or rash and arthritis
– 2.3 %
• Leukopenia due to bone marrow suppression– 1.4 %
• Pancreatitis1 4 %– 1.4 %
• Nausea– 1.4 %
Biologics for IBD
• Infliximab (Remicade®) - CD & UC
• Adalimumab (Humira®) - CD
• Certolizumab (Cimzia®) - CD
22
Infliximab, Adalimumab, Certolizumab
• Not usually first line, but more of such a l i C h ’ dirole in Crohn’s disease
• Infliximab now in CD & UC
• Expensive– $2,500/infusion or injection
Sid ff t• Side effects– infusion reactions, allergic problems,
opportunistic infections, sepsis
• Rapid onset of response
18
Infusion Reactions (cont.)Infusion Reactions (cont.)
Reaction % Infusions
Nonspecific symptoms 4%
Pruritus/urticaria 1%
Cardiopulmonary reactions 1%
C bi ti d t l iCombination dermatologicand cardiopulmonary reactions 0.1%
Serious reactions 0.5%
Schaib le T. Can J Gastroenterol. 2000;14:29C.
23
Infections with Anti-TNF Agents
• Opportunistic
• TB– Often disseminated or extra-pulmonary
• Pneumonia, histoplasmosis, coccidioidomycosis, listeriosis and pneumocystosispneumocystosis
• Bacterial infections including sepsis
• Should not be given to patients with a clinically important, active infection
Other Issues with TNF Inhibition
• HBV reactivation
• Contraindication in class III/IV CHF• Contraindication in class III/IV CHF
• Caution should be exercised when considering treatment of patients with a current or a past history of malignancy or other risk factors such as chronic obstructive pulmonary disease (COPD)
• Demyelinating disorders
• Consider discontinuation for significant CNS adverse reactions
• Hepatic reactions
• Lupus-like syndrome
24
UC Treatments
Therapeutic Pyramid for Active UC
SevereSevereSurgerySurgery
ModerateModerate
Systemic CorticosteroidsSystemic Corticosteroids
SurgerySurgery
AZA/6AZA/6--MPMP
CyclosporineCyclosporine
Infliximab Infliximab
MildMild
AminosalicylatesAminosalicylates
Oral SteroidsOral Steroids
25
Smoking and Ulcerative Colitis
• Cigarette smokingH t ti ff t d l t d f– Has protective effect on development and course of UC including extraintestinal and postsurgical events
– Nicotine therapy (gum, patch, enema) has mixed results
– Restart smoking in severe or refractory colitis?
E k lik l t d l t i UC
Hanauer SB. Nat Clin Pract Gastroenterol Hepatol. 2004;1:26.Ingram JR, et al. Aliment Pharmacol Ther 2004;20:859.
• Ex-smokers more likely to develop extensive UC (second age peak > 40 years)
Ulcerative Colitis: Induction of Remission
• Mild/moderate disease– Aminosalicylate
• Topical therapy (distal disease)– Canasa® supp & Rowasa® enema
• Oral therapy (extensive disease)– Sulfasalazine, Pentasa®, Asacol®, Colazal®
(balsalazide)(balsalazide)
26
Chemical Structure of 5-Aminosalicylate (Mesalamine) and Its Pro-Drugs:
Sulfasalazine, Balsalazide and Olsalazine
55--aminosalicylic acidaminosalicylic acid SulfasalazineSulfasalazine
BalsalazideBalsalazide OlsalazineOlsalazine
55--ASA Delivery SystemsASA Delivery Systems
PENTASA®
ASACOL®®
SASP/OLS/BALS
ENEMA
SUPP
JEJUNUM / ILEUM / ASC / DES / SIG / RECT
27
ASCEND I & II:Pooled Data
• 423 analyzable patients with moderately active UC d i d t l l iUC randomized to oral mesalamine
– 4.8 g/day (800 mg tablets) or 2.4 g/day (400 mg tablets) x 6 weeks
• Treatment with mesalamine 4.8 g/day provided a statistically significant efficacy benefit over 2.4 y g yg/day in moderately active disease
• Both doses of mesalamine had similar safety profiles and both were well tolerated
Hanauer et al. DDW 2005
Oral (2.4 g) vs. Rectal (4 g)Oral (2.4 g) vs. Rectal (4 g)Mesalamine for Distal UCMesalamine for Distal UC
% R
esp
on
se%
Res
po
nse
3030
4040
5050
6060
7070
8080
9090
100100
Oral Oral
RectalRectal
CombinedCombined
%%
Safdi. Am J Gastroenterol 1997
00
1010
2020
3030
1 week1 week 2 weeks2 weeks 3 weeks3 weeks 6 weeks6 weeks
28
Frequency of Topical Mesalamine for Maintenance
of Distal UC90
% R
emis
sio
n
30
40
50
60
70
80
90
QHS
QOD
Q3D
Placebo
Miner. Gastroenterol 1994;106:A736
0
10
20
6 wks 12 wks 24 wks
Placebo
29
Ileo-anal pouch anastomoses (IPAA)
Complications of Surgery:Ileal Pouch-Anal Anastomosis (IPAA)
– Pelvic sepsis
– Leakage
– Incontinence
– Intestinal obstruction
– Anastomotic strictures
Potential short-term complications
Potential long-term complications
Anastomotic strictures
– Sexual dysfunction
– Pouchitis
– Female infertility
Lichtenstein G. The Clinician’s Guide to Inflammatory Bowel Disease. SLACK;2003:127–129.
30
Complications of UC Surgery• Mortality - (<0.5%)1
• 3-10 stools/24 hrs so bowel pattern not normal1
• Impotence - (1 5%)2Impotence (1.5%)
• Pouchitis - (10-60%)1
• Small bowel obstruction - (20%)1
• Decrease in female fertility - (56-98%)3-5
• Colectomy with ileorectal anastomosis preserves female fertility
• Pouch-vaginal fistula - (4%)1
1Sagar PM, Pemberton JH. In Satsangi J, Sutherland L, et al, eds. Inflammatory Bowel Diseases. Spain: Elsevier Limited; 2003:491 511.
2Pemberton JH, et al. Ann. Surg. 1987;206(4):504-513. 3Olsen, KO, et al. Gastroenterology. 2002;122:15-19.
4Johnson P, et al. Dis Colon Rectum. 2004;47;1119–1126. 5Gorgun E, et al. Surgery. 2004;136(4):795–803.
Ileal PouchFunctional Outcome
Age in Years
10 year postoperative <45
46-55
56-65 >65
# of BM / 24 Hours 5.5 5.7 6.2 4.6Never Incontinent (%) 56 46 42 33
Delaney CP, et al. Ann Surg. 2003;238:221-228.
Nocturnal Seepage (%) 39 48 39 60
Majority of patients had UC; other diseases included Crohn’s disease, indeterminate colitis, familial polyposis, and cancer
31
Ileal Pouch:Cumulative Incidences Pregnancy
M thControls
Before C l t
After IPAAMonths
Controls (n=914)
Colectomy (n=84)
IPAA (n=149)
12 75% 78% 18%*
24 82% 85% 27%*
60 88% 90% 36%*
*P<0.001 vs. Controls
Olsen KO, et al. Gastroenterology. 2002;122:15-19.
Crohn’s disease treatment
32
33
34
Maintenance Therapies for Ulcerative Colitis
A i li l• Aminosalicylates
• Azathioprine/6-MP
• Infliximab (Remicade®)
35
Mortality and IBD
• IBD patients have an elevated mortality rate of 0.5% per year
• Extensive colitis and higher age (> 50 years) at diagnosis increase• Extensive colitis and higher age (> 50 years) at diagnosis increase the risk for a fatal outcome in UC
• Greatest hazard ratio (HR)
– UC – age group 40 to 59 years (HR 1.79)
– CD – age group 20 to 39 years (HR 3.82)
• IBD is associated with an overall small increase in mortality rate greatest in relative terms in younger subjects but in absolute terms in the elderly
Card T, et al. Gastroenterology. 2003;125:1583.Winther KV, et al. Gastroenterology. 2003;125:1576.
Final Points• There is no “one size fits all” to IBD therapy
– Therapy and decision making are tailored to the individual
• Algorithms are based upon available evidenceAlgorithms are based upon available evidence
– Evidence is in constant flux
• Success of algorithms depends upon optimization of each step of therapy and considerable judgment about each outcome
– Skillful application of medical therapy makes all the diff i tdifference in outcomes
• Need for better treatments since many only work about 50% of the time
• Success of newer medications have opened new doors for investigation
36
When to Suspect IBDInstead of IBS
• Red flags
If d fl IBD lik l• If no red flags, IBD unlikely
• Even if IBD present in some sort of subclinical state such that “red flags” are negative, hard to justify more than symptomatic rx
• … and that means GI specific care not needed itheither
• Kids are slightly different and need close attention and f/u to growth
*
37
Do Not Use the Panelsthat are Marketed
to Distinguish IBS from IBD (Prometheus)
• Useless in this setting
• Main utility is persons with indeterminate colitis who require surgery and may need a permanent ileostomy if disease is more C h ’ likCrohn’s-like
• I have not ordered one in years
Supplementary Materials
38
Genetics Issues
Familial Patterns of Inheritance in IBD
• Relative risk 14-15 times higher among first-degree relatives than the general population
– Prevalence in family members
• 4.6% parents
• 2.6% siblings
• 1.9% children
• Concordance in affected parent-child pairs
– 75% disease type
Sands BE. Crohn’s Disease. In: Feldman M, Friedman LS, Sleisenger MH, eds. Sleisenger & Fordtran’s Gastrointestinal and Liver Disease. Philadelphia, PA: Saunders; 7th ed. 2002:2009.
Satsangi J, et al. Gut. 1996;38:738. Lashner BA, et al. Gastroenterology. 1986:91:1396.
– 63% extent
– 70% extraintestinal manifestations
– 85% smoking history
39
Genetics and IBD
• Greater concordance for CD than for UC
Twin Studies Concordance
Identical Fraternal
CD 58% 0%
UC 18% 4%
Stenson WF, et al. Inflammatory bowel disease. In: Yamada T et al., eds. Textbook of Gastroenterology. Philadelphia, PA: Lippincott Williams & Wilkins; 4th Ed. 2003:1699.
Orholm M, et al. Scand J Gastroenterol. 2000;35:1075.
Miscellaneous Reproductive and Sexual Health Issues
40
Gender-Related Considerations in IBD
Slide courtesy of Dr. Sunanda Kane, Mayo Clinic
Women Men
Reproductive issues
fertility after IPAA or proctocolectomy
risk of relapse if disease active at
time of conception
fertility with sulfasalazine
Disease-related concerns
concern re: body stigma,
loss of bowel control
—
Sexuality sexual activity because of dyspareunia,
abdominal pain, depression, etc
libido and sexual satisfaction after proctocolectomy; depression effects
Women with Restorative Proctocolectomies:
Satisfaction With Sexual Relationships
• 22% improved
• 51% unchanged
• 26% less satisfactory
• Overall 86% moderately to extremely % y ysatisfied
Bambrick M, et al. Bambrick M, et al. Dis Colon Rectum.Dis Colon Rectum. 1996;39:6101996;39:610--614.614.
Slide courtesy of Dr. Sunanda Kane, Mayo Clinic
41
Pouch Function and Pregnancy
• Questionnaire study of women with IPAA– 49 deliveries in 29 women (25 vaginal)
– 6 pouch-related complications (2 during pregnancy)
– Increased stool frequency reported during pregnancy
– Delivery method did not influence incontinence, stool frequency
Ravid A. Dis Colon Rectum 2002; 45:1283-88.
Slide courtesy of Dr. Sunanda Kane, Mayo Clinic
Pregnancy on IBD:Does Pregnancy Change Course?
• European cohort followed over 10 years
• 580 pregnancies, 403 prior to, 177 after diagnosis of IBD
• Rate of spontaneous Ab higher after dx
• C section rate higher after IBD dx
• Rate of relapse decreased in years following pregnancy in both UC and CD
Riis L. Am J Gastroenterol 2006; 101:1539-45.
Slide courtesy of Dr. Sunanda Kane, Mayo Clinic
42
Summary: Safety of IBD Medications During Pregnancy
Category B Category C Category D Category X
Loperamide Ciprofloxacin Azathioprine† Methotrexate
Mesalamine Cyclosporine 6-Mercaptopurine† Thalidomide
Balsalazide Diphenoxylate
Corticosteroids Olsalazine
Sulfasalazine Tacrolimus
*Safe for use after first trimester. *Safe for use after first trimester. ††Increasing use in pregnancy.Increasing use in pregnancy.
Briggs GG, et al. Briggs GG, et al. Drugs in Pregnancy and Lactation.Drugs in Pregnancy and Lactation. 5th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 1998. 5th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 1998. Physician’s Desk ReferencePhysician’s Desk Reference®®. 57th ed. Montvale, NJ: Thompson PDR; 2003.. 57th ed. Montvale, NJ: Thompson PDR; 2003.
Infliximab
Metronidazole*
Slide courtesy of Dr. Sunanda Kane, Mayo Clinic
Mode of Delivery andFecal Incontinence
• Survey study in Wales (n = 229)Survey study in Wales (n = 229)
• No higher CS rate in IBD
• 28% vs. 2% normal had fecal incontinence after vaginal delivery
• Results need to be confirmedResults need to be confirmed
Ong JPL. Inflamm Bowel Dis 2007;13:1391-94.
Slide courtesy of Dr. Sunanda Kane, Mayo Clinic
43
IBD in Pregnancy: Summary
• Pregnancy outcomes best if patient in remission at time of conception
• CD may increase the risk of preterm birth and low birth weight, but UC may not
• No significant increase in risk of congenital abnormalities or maternal complications
• Women with IBD have a higher rate of cesarean sections
• Pregnancy may not increase the risk of relapse or significantly increase disease activityincrease disease activity
• Overall, outcomes for women with IBD are similar to those for general population
Slide courtesy of Dr. Sunanda Kane, Mayo Clinic
Safety of IBD Medications in Breast-Feeding
Safe to Use When Warranted
Limited Data Available Contraindicated
Oral mesalamine Azathioprine Methotrexate
Topical mesalamine 6-Mercaptopurine Cyclosporine
Sulfasalazine Infliximab MetronidazoleSulfasalazine Infliximab Metronidazole
Corticosteroids Tacrolimus Ciprofloxacin
Physicians’ Desk ReferencePhysicians’ Desk Reference®®. 57th ed. Montvale, NJ: Thompson PDR; 2003.. 57th ed. Montvale, NJ: Thompson PDR; 2003.
Slide courtesy of Dr. Sunanda Kane, Mayo Clinic
44
Incidence of Abnormal Pap Smears in IBD
• Abnormal Pap smears associated with both infection and progression to cancerboth infection and progression to cancer
• Incidence study of women with IBD and a history of abnormal Pap smears
• Adjusted for smoking, OCP use and parity • Women with IBD were more likely to have
an abnormal Pap• Use of azathioprine increased risk 3 fold
Kane SV Am J Gastro 2007 in press
Slide courtesy of Dr. Sunanda Kane, Mayo Clinic
