managing coexistent inflammatory bowel disease in patients with psc themos dassopoulos, m.d....
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Managing Coexistent Inflammatory Bowel Disease in Patients with PSC
Themos Dassopoulos, M.D.Director, Baylor Center for IBD
www.centerforibd.com
April 24, 2015
No disclosures
The Basics!• What is IBD? • You’re not alone - How common is IBD?• It’s not your fault - What causes IBD?• What are the symptoms and complications of IBD?• Until there is a cure - How is IBD treated?• Is IBD different in patients with PSC?• Am I what I eat? - What is the role of diet?• What is the role of stress?• Tips for managing IBD and staying well
Inflammatory Bowel Diseases (IBD)
• Disorders of chronic bowel inflammation• Inappropriate immune reaction to normal bacteria in
genetically susceptible individuals
Types of IBD
CROHN’S DISEASE (CD) • Patchy, full-thickness inflammation• Mouth to anus involvement,
mostly lower small intestine and colon• Fistulas, abscesses, strictures• Worsens with smoking
IndeterminateColitis
10%-15%
ULCERATIVE COLITIS (UC)• Continuous, inflammation of the
lining (mucosa) of the colon• Colon only
Inflammatory Bowel Diseases (IBD)
• Disorders of chronic bowel inflammation• Inappropriate immune reaction to normal bacteria in
genetically susceptible individuals
• The IBDs are not– Food allergies– Food sensitivities– Infections– Irritable bowel syndrome (IBS)
How common is IBD?
• 1 to 1.5 million Americans suffer from IBD• 80,000 hospitalizations per year• 18,000 surgeries per year
• CD medical costs $18,963 / year• UC medical costs $15,020 / year
• Increasing in the pediatric population• Increasing in the developing world
What causes IBD?
Inflammation
Abnormal gut flora• Diet• Antibiotics• Infections
Modifiers:• Smoking• NSAIDs
• Defective clearance of bacteria• Mucosal inflammatory responses• Barrier function of mucosa
EnvironmentGenetics
Over 150 genes!
Over 160 genes500-1000 microbial species
Multiple environmental factors
Over 160 genes500-1000 microbial species
Multiple environmental factors
Each IBD patient is unique The course of the disease differs
from person to person
• Bloody diarrhea• False alarms• Abdominal pain
Ulcerative Colitis
Endoscopic scoreUlcerative Colitis
Crohn’s disease
Inflammatory PenetratingFistulae and Abscesses
Stricturing
PainDiarrhea
PainDistensionVomitingFear of eatingWeight lossRumbling bowel sounds
Presentations of Crohn’s
PainFeverNight sweatsWeight loss
Inflammatory PenetratingFistulae and Abscesses
Stricturing
PainDiarrhea
PainDistensionVomitingFear of eatingWeight lossRumbling bowel sounds
Presentations of Crohn’s
PainFeverNight sweatsWeight loss
Inflammatory PenetratingFistulae and Abscesses
Stricturing
PainDiarrhea
PainDistensionVomitingFear of eatingWeight lossRumbling bowel sounds
Presentations of Crohn’s
PainFeverNight sweatsWeight loss
Inflammatory PenetratingFistulae and Abscesses
Stricturing
PainDiarrhea
PainDistensionVomitingFear of eatingWeight lossRumbling bowel sounds
Presentations of Crohn’s
PainFeverNight sweatsWeight loss
Joint Peripheral arthritisSacroiliitisAnkylosing spondylitis
Skin Erythema NodosumPyoderma Gangrenosum
Liver Primary Sclerosing Cholangitis
Eye EpiscleritisIritis
Extra-intestinal Manifestations
Other complications• Anemia (multiple causes)• Steroid-dependence• Osteoporosis• Malabsorption (CD of the small bowel)– Vitamin B12– Vitamin D
• Colorectal cancer (UC and CD of the colon)• Thrombosis and pulmonary embolism• Toxic megacolon
Risk of colon cancer in colitis
• Risk was greater than 20% in older studies
• The risk has declined significantly in more recent studies
• The risk remains high in patients with:– Longstanding pancolitis with significant mucosal injury– PSC: Approximately 30%
Patients with PSC and colitis should have an
ANNUAL colonoscopy
Clinical features of colon cancer inpatients with colitis and PSC
• Younger at diagnosis of colon cancer
• More advanced, right-sided colon cancer
• Possibly higher cancer risk if dominant stenosis
• The increased risk of colon cancer persists after liver transplantation
Patients with PSC and colitis should have an ANNUAL
colonoscopy even after liver transplantation
Other complications• Anemia (multiple causes)• Steroid-dependence• Osteoporosis• Malabsorption (CD of the small bowel)– Vitamin B12– Vitamin D
• Colorectal cancer (UC and CD of the colon)• Thrombosis and pulmonary embolism• Toxic megacolon
Quality of life
• Bowel function• Depression• Work and school attendance• Reproductive decisions
Informed, Empowered
Patient
PreparedProviders
CommunityHealth System
SelfManagement
Support
ClinicalInformation
Systems
DecisionSupport
DeliverySystem
Wellness, improved function and quality of lifeMonitoring and prevention of complications
Chronic Care Model
Wagner EH Effective Clinical Practice 1998
Goals of Therapy• Induction of remission• Maintenance of remission• Improved quality of life
Goals of Therapy• Induction of remission• Maintenance of remission• Improved quality of life• Prevention of complications• Restoring and maintaining nutrition• Optimization of surgical intervention
Goals of Therapy• Induction of remission• Maintenance of remission• Improved quality of life• Prevention of complications• Restoring and maintaining nutrition• Optimization of surgical intervention• Mucosal healing
Mucosal Healing
Before therapy After therapy
Mucosal Healing results infewer hospitalizations and surgeries
Classes of IBD therapiesAminosalicylates(UC, CD)
• Sulfasalazine (Asulfidine)• Mesalamine (5ASA)
(Asacol, Pentasa, Colazal, Lialda, Apriso)• 5ASA enemas and suppositories
(Rowasa enemas, Canasa suppositories)
Classes of IBD therapiesAminosalicylates(UC, CD)
• Sulfasalazine (Asulfidine)• Mesalamine (5ASA)
(Asacol, Pentasa, Colazal, Lialda, Apriso)• 5ASA enemas and suppositories
(Rowasa enemas, Canasa suppositories)
Antibiotics (CD)* • Ciprofloxacin (CD) (Cipro)• Metronidazole (CD) (Flagyl)
*Antibiotics are used for CD of the colon and to prevent post-operative recurrence of CD. They are not used in UC.
Classes of IBD therapiesAminosalicylates(UC, CD)
• Sulfasalazine (Asulfidine)• Mesalamine (5ASA)
(Asacol, Pentasa, Colazal, Lialda, Apriso)• 5ASA enemas and suppositories
(Rowasa enemas, Canasa suppositories)
Antibiotics (CD) • Ciprofloxacin (CD) (Cipro)• Metronidazole (CD) (Flagyl)
Corticosteroids(UC, CD)
• Prednisone• Budesonide (ileocolic, colonic release)
(Entocort, Uceris)• Rectal (hydrocortisone enemas, foam)
(Cortenema, Cortifoam)• IV (methyprednisolone,hydrocortisone)
Classes of IBD therapies
Immunomodulators
• 6-mercaptopurine (CD, UC)(Purinethol)• Azathioprine (CD,UC) (Imuran)• Methotrexate (CD)
Classes of IBD therapies
Immunomodulators
• 6-mercaptopurine (CD, UC)(Purinethol)• Azathioprine (CD,UC) (Imuran)• Methotrexate (CD)
Anti-TNF • Infliximab (CD,UC) (Remicade)• Adalimumab (CD,UC) (Humira)• Certolizumab (CD) (Cimzia)• Golimumab (UC) (Simponi)
Classes of IBD therapies
Immunomodulators
• 6-mercaptopurine (CD, UC)(Purinethol)• Azathioprine (CD,UC) (Imuran)• Methotrexate (CD)
Anti-TNF • Infliximab (CD,UC) (Remicade)• Adalimumab (CD,UC) (Humira)• Certolizumab (CD) (Cimzia)• Golimumab (UC) (Simponi)
Anti-4 integrin • Natalizumab (CD) (Tysabri)• Vedolizumab (UC, CD) (Entyvio)
Lessons we have learned Treating the disease early gives the best results
Adherence to treatment is key
Rectal therapies are critical for UC
Steroids do not heal the inflammation of CD
The most effective medications are– Immunomodulators – Anti-TNF agents– Immunomodulators + anti-TNF (most effective)
Benefits far outweigh the risks
The role of surgery in UC
• Surgery is not necessarily a bad outcome
• Colectomy cures ulcerative colitis
Proctocolectomy with end-ileostomy
Proctocolectomy withileal pouch-anal anastomosis
Kirat and Remzi, Clin Colon Rectal Surg 2010
Ileum
Colon
Ileal Pouch
The role of surgery in CD
• Bowel resection for CD removes the diseased bowel and allows a fresh start
• BUT, prevent post-operative recurrence
Strictureplasty
Primary Sclerosing Cholangitis in IBD
• Over 60% of patients with PSC also have IBD:‒ UC 80%‒ CD 10%‒ Indeterminate colitis 10%
• 3–8% of patients with UC have PSC
• 1–3% of patients with CD have PSC
• The activities of IBD and PSC are independent
Every patient with PSC should be screened for colitis
Treating the IBD does not affect the PSC
Colitis with coexistent PSC is “different”
• Pancolitis with rectal sparing• Mild ileitis• Mild activity – occasionally asymptomaticLess likely to require colectomy because of
resistant colitis• Increased mortality from colon cancer, liver
failure, and cholangiocarcinoma
What happens after liver transplantation?IBD• Variable course of colitis• Risk of colon cancer remains high
Liver Disease• Increased risk of PSC recurrence in patients with
intact colons• The presence or severity of IBD does not influence
the occurrence of recurrent PSC or patient survival
What happens after colectomy?
After ileal-pouch anal anastomosis• Increased risk of pouchitis• No increased risk of pouch failure • Similar quality of life• Higher long-term mortality
After end ileostomy• Parastomal varices (40-50%)
Diet and IBD
• The Western diet is one of the causes of IBD
• No particular food or diet cures IBD
• Some patients report improved symptoms with specific diets
• BUT, diets can be restrictive and difficult to follow
Which diet might help prevent IBD?
• Lower intake of n-6 polyunsaturated fatty acids– Arachidonic acid and Linoleic acid
(red meat, margarines, oils derived from soya, sunflower, rapeseed, poppyseed, and corn)
• Higher intake of n-3 polyunsaturated fatty acids– Perilla oil, fish oil, sardines, salmon
• Higher intake of dietary fiber• Lower intake of sugars
Diet: Specific situations• Coexistent conditions – avoid the food culprit– Lactose or fructose intolerance– Celiac disease– Non-celiac gluten sensitivity– Irritable bowel syndrome – FODMAP diet– Food allergies
• Flares– Bland diet (avoid fat, caffeine, alcohol and fiber)
• Obstruction– Low residue diet (avoid insoluble fiber: seeds, nuts,
beans, green leafy vegetables, wheat bran)
Stress and IBD
• Many patients report flares precipitated by stress– It’s not only what the patient eats… but also what eats the patient
• Anxiety, depression, support structures, coping strategies, and perception of illness affect course of illness
• Patients should be screened for psychological distress
• Psychological interventions improve quality of life, anxiety and depression
Tips for managing IBD and staying well
• Educate yourself• Learn your disease• Come prepared• Ask questions• Be your own advocate• Manage stress and diet• Have a plan
Tips for managing IBD and staying well
• Educate yourself• Learn your disease• Come prepared• Ask questions• Be your own advocate• Manage stress and diet• Have a plan
• Avoid aspirin and NSAIDs• Stop smoking• Take your medications• Maintain bone health• Be vigilant about infection• Keep vaccinations up-to-date• Get scoped annually
(if you have colitis and PSC)
Putting it all together
• The IBDs are complex diseases– Each patient is unique
• Chronic disease management– Patient education and empowerment– Collaboration between primary provider,
gastroenterologist, hepatologist and other providers• The future of IBD care and research is bright!
Additional slides
Aminosalicylates
• Sulfasalazine • Mesalamine (5ASA)• 5ASA enemas and suppositories
• Use: UC, Mild Crohn’s colitis• AE: Paradoxical diarrhea, nephrotoxicity
Antibiotics
• Ciprofloxacin• Use: Mild Crohn’s colitis
Perianal disease• AE: Tendinitis, tendon rupture, C. difficile
•Metronidazole• Use: Mild Crohn’s colitis
Prevention of postoperative recurrencePerianal disease
• AE: Peripheral neuropathy
Corticosteroids
• Prednisone• Budesonide• Ileocolic release • Colonic release
• Topical • Hydrocortisone enemas, foams and suppositories• Budesonide foam
• IV (methyprednisolone,hydrocortisone)
• Use: Induction of remission in UC and CDNOT maintenance
Thiopurines• Azathioprine Mercaptopurine
• Maintenance of steroid induced remission (CD,UC)• Perianal disease (CD)• Prevention of post-operative recurrence (CD)• Reduction of anti-TNF immunogenicity
Leukopenia (10-20%) Non-melanoma skin cancer
Transaminitis (10-20%) Bacterial infections (with neutropenia)
Pancreatitis (3%) Reactivation of HBV
Herpes zoster Lymphoma (4-6/10,000/year)
CMV colitis Nodular regenerative hyperplasia
Methotrexate
• Maintenance of steroid induced remission (CD)• Reduction of anti-TNF immunogenicity (CD,UC)
Nausea, emesis, fatigue (give folic acid)StomatitisLeukopeniaLiver fibrosis and cirrhosisInterstitial pneumonitis and pulmonary fibrosisInfections are rare
No reports of lymphoma
Anti-TNF• Infliximab (Remicade), adalimumab (Humira),
certolizumab pegol (Cimzia), golimumab (Simponi)• Induction and maintenance of remission (CD,UC)• Perianal disease (CD)Infusion reactions Cutaneous reactionsHepatotoxicity CytopeniaInfections: Reactivation of TB, Herpes zoster, HBVEndemic: Histoplasmosis, coccidioidomycosis, blastomycosisOpportunistic: Aspergillosis, cryptococcosis, pneumocystisMelanomaNo proof of increased incidence of lymphoma
Anti-TNF a agents• Similar efficacy – Induction: ≈ 60% response– Maintenance: ≈ 40% response
• Similar safety• Anti-drug antibodies (ADA) (10-15%/year)® Loss of response
• Concomitant immunomodulators – Decrease ADA 14.6% on infliximab vs. 0.9% on combo– Enhance efficacy 44.4% on infliximab vs. 58.8% on combo
• Similar efficacy in luminal disease– Infliximab is faster-acting
• Infliximab is more effective for perianal disease• Similar safety and immunogenicity
Choice of agent also depends on:Cost ConvenienceCompliance
Considerations in selecting anti-TNFa
Anti-Integrin therapies
MAdCAM-1
α4β7
T cell
α4β7
MAdCAM-1T cell
NATAnti-α4
Anti-Integrin therapiesNatalizumab (Tysabri®)
Anti-4 Blocks 47 and 41
Prohibitive risk of PML if JCV Ab (+)
VEDAnti-α4β7
MAdCAM-1T cell
NATAnti-α4
Anti-Integrin therapiesNatalizumab (Tysabri®)
Anti-4 Blocks 47 and 41
Prohibitive risk of PML if JCV Ab (+)
Vedolizumab (Entyvio®)Anti-47
Gut specificNo risk of PML