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