APGNN ANNUAL MEETING Building a Strong Foundation

APGNN ANNUAL MEETING Building A Strong Foundation

October 21 – 22, 2011 Orlando, FL

Association of Pediatric Gastroenterology and Nutrition Nurses

October 2122, 2011

Dear APGNN Meeting Participants:

Welcome to Orlando! We are excited to present an excellent program! Our Program Committee chair, Patty Bierly, and her committee have been working hard since last year to ensure a high quality, timely and exciting educational meeting. Thank you!

Please take some time to read through the syllabus. Remember that your comments help us to plan next year’s program! Plan to attend committee meetings on Friday afternoon, please see the schedule for details. This is a wonderful way to find out how YOU can become more involved in APGNN. We are only as strong as our members! No commitment necessary, just come and find out what these committees are all about!

Join us for breakfast and an APGNN update on Friday morning at 7:30. Don’t forget the annual APGNN Social Event on Friday evening at 6:00. This is a fun, relaxed way to network and meet friends.

I would like to extend my thanks to the wonderful APGNN leadership team. I am wrapping up my term as President and I can say without a doubt that I would have been lost without their support and encouragement. Being APGNN President has been a distinct honor and privilege. We will be saying goodbye to Mary Alice Tully who finishes her term as Past President. Mary Alice, you have been amazing and we are so grateful to you for your service! Your next President will be Lisa Philichi who brings a wealth of experience and enthusiasm to the role!

Finally, I would like to extend a heartfelt thanks to Kathleen Schwarz, MD, NASPGHAN President, and NASPGHAN leadership. You have been so welcoming to me personally and as APGNN President. APGNN deeply appreciates your support and we look forward to a continued strong relationship. A special thank you to NASPGHAN staff: Margaret Stallings, Kate Ho and Kim Rose. We know we cannot do this without you and we are so grateful for your hard work and patience!

Sincerely,

Robin Shannon, MS, RN, CPNP President, APGNN 20092011 Please check our website, www.apgnn.org, for ongoing updates throughout the year! Your updated leadership team contact information can be found there. Please reach out to us!

President Robin Shannon, MS, RN, CPNP Newsletter University of Minnesota Children’s Hospital Shabina Walji-Virani, RN, MSN, CPNP 420 Delaware St. SE, MMC 185 Pediatric Gastroenterology, Hepatology and Nutrition Minneapolis, MN 55455 Children’s Medical Center, Legacy Work: 763-355-5060 76009 Preston Road, Suite P2600 Fax: 763-355-5060 Plano, TX 75024 Email: [email protected] Work: 469-303-4269 Email: [email protected] Past President Mary-Alice Tully, MSN, PNP-BC Patient and Family Education Boston Children’s Hospital Laurie Weber 300 Longwood Ave Marshfield Clinic Boston, MA 02115 1000 North Oak Ave Work: 617-355-7020 Marshfield, WI 54449 Fax: 617-730-0495 Work: 715-387-5251 Email: [email protected] Fax: 715-389-3066 Email: [email protected] President-Elect Lisa Philichi, RN, MN, ARNP Program Chair Mary Bridge Health Center Patricia Bierly, RN, MSN, CPNP 311-W3-GI South L. Street The Children’s Hospital of Philadelphia th Tacoma, WA 98415-0299 34 and Civic Center Blvd Work: 253-403-3536 Philadelphia, PA 19104 Fax: 253-403-7986 Work: 215-590-0420 Email: [email protected] Fax: 215-590-3606 Email: [email protected] Secretary Diane Kocovsky, APRN Research and Publications Boys Town National Research Hospital Clare Ceballos, MA, BC-PNP Omaha, NE 68144 The Mount Sinai Medical Center Work: 402-778-6851 One Gustave L Levy Place, Box 1656 Fax: 402-778-6826 New York, NY 10029-6578 Email: [email protected] Work: 212-241-7349 Fax: 212-876-1729 Treasurer Email: [email protected] Shari Huffman, APRN Nemours Children’s Clinic Clinical Practice Committee Pediatric Gastroenterology and Nutrition Emmala Ryan Shonce, RN, MSN, FNP-C 807 Children’s Way Levine Children's Hospital Jacksonville, FL 32207 Work: 904-697-3501 Pediatric Gastroenterology, Hepatology and Nutrition Email: [email protected] 1001 Blythe Blvd MCP Suite 200 F Charlotte, North Carolina 28203 Membership Fax:(704) 381-6851 Teresa Carroll, RN, MSN, PNP Phone: (704) 381-8898 Pediatric GI & Nutrition Associates Email: [email protected] 3196 S. Maryland Parkway #309 Las Vegas, NV 89109 Work: 702-791-0477 Fax: 702-791-6831 Email: [email protected]

The Mission of APGNN

The formation and ongoing mission of the Association of Pediatric Gastroenterology and Nutrition Nurses is to:

Promote the professional development and recognition of pediatric nurses as experts in their field

Promote excellence in the care of families with children with gastroenterology and nutritional illnesses

Our Goals

The APGNN was founded upon and recognizes the following organizational goals:

Promote nursing research and publication of findings

Promote education for patients, families, nurses, allied health professionals, and physicians

Establish standards of practice

Create a Pediatric Gastroenterology/Nutrition Network

Support role development through attendance and participation in conferences and development of teaching materials

The APGNN web site is: www.apgnn.org A membership application is also available through this web site. Please be patient as this site continues to evolve.  For changes in your membership database go through the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition NASPGHAN web site: www.naspghan.org Helpful practice guidelines and patient and family brochures are also accessible through this website

2011 APGNN Educational Conference “Building a Strong Foundation” Supported in part through restricted educational grants from:

A division of Abbott Laboratories, Inc.

Annual APGNN Social Event Friday October 21 6:00 pm

Sponsored in part by

Please join us for appetizers, networking and socializing! Celebrate APGNN!

5 Building A Strong Foundations October 21- 22, 2011 Orlando, Florida Friday, October 21, 2011 – Ireland ABC

7:30 - 8:15 Registration/Breakfast/ Welcome/Board Introduction /Business Meeting

8:15 -9:15 Keynote Address Set for Success: Creating a Strong Foundation in Practice Donna Cardillo, RN, MA 60 minutes= 1

9:15 - 10:15 Don’t’ Get Stuck in the Gut Rut-Nutrition GI patient Janelle Peterson RD, LD, CNSC 60 minutes= 1

Break 15 minutes

10:30 - 11:15 Common- Uncommon Presentation of Celiac Disease Ritu Verma, MD 45 minutes= 0.75

11:15- 12:00 pm Caring for Children Pre and Post Liver Transplant Jody Weckwerth, RD, PA-C 45 minutes-0.75

12:00-1:30 Posters and Lunch

1:30 -3:00 Multiple Aspects of IBD Robert Baldassano, MD 45 minutes- 0.75

Improving Health Maintenance in Children with IBD Diane Kocovsky, APRN, MS 45 minutes-0.75

Break 15 minutes

3:15- 4:00 Enteral Nutrition for Crohn’s Disease: A Canadian Experience Cynthia King- Moore, BScHN,PDt and Anthony Otley, MD,Mac FRCPC 45 minutes-0.75

4:00-415 Conference Wrap up 15 minutes-0.25

4:30 APGNN Committee Meetings – Open to all interested APGNN members Membership – Ireland ABC Research & Publications - Scribe Newsletter – Ireland ABC Patient & Family Education - Yeoman Clinical Practice – Knave Program - Captain

6:00pm Social Event (Watercress Cafe) (All registered APGNN conference attendees invited) APGNN Excellence in Mentoring Award presentation APGNN Newsletter Award presentation

6 APGNN Annual Meeting Building A Strong Foundations October 21- 22, 2011 Orlando, Florida Saturday, October 22, 2011-Ireland ABC

8:00 Registration/Breakfast

8:15 -9:00 Resources for the Adolescent Transitioning Patient Maureen Kelly, RN, MSN, CPNP 45 minutes=.75

9:00- 10:00 Intestinal Rehabilitation: The long and Short of it. Danielle Sebbens, DNP, CPNP-PA/AC 60 minutes= 1

Break 15 minutes

10:15 - 10:45 Posters of Distinction Clare Ceballos, MA, BC-PNP moderator 30 minutes= .5

10:45- 11:00 Excellence in Education Award

11:00-12:00 Zebras 60 minutes- 1 Shabina Walji-Virani, RN, MSN, CPNP-PC Millie Boettcher, MSN, CRNP, CNSN Saundra Matthews, RN, BSN

12:00-1:30 NASPGHAN Business Lunch

1:30 -3:00 Aero-digestive Disorders and Motility Studies Rachel Rosen, MD 45minutes-0.75

Indications and Complications of Pediatric Endoscopy Petar Mamula, MD 45minutes-0.75

Break 15 minutes

315- 4:15 Constipation- What to do when standard therapy fails Kimberly Jarczyk, MSN, CRNP 45minutes-0.75 Tara Matthews, PhD 45minutes-0.75

4:15-4:30 Conference Wrap up 15 minutes-0.25

This educational activity has been submitted to the Society of Gastroenterology Nurses and Associates, Inc. for approval. The Society of Gastroenterology Nurses and Associates, Inc. is accredited as an approver of continuing education in nursing by the American Nurses Credentialing Center’s Commission on Accreditation.

7 VESTED INTEREST DISCLOSURE DECLARATION It is the policy of NASPGHAN and the ANCC Commission on Accreditation and the Society of Gastroenterology Nurses and Associates, Inc. (SGNA), the accreditors of this program, that all presenters participating in any SGNA-approved educational program must disclose any actual, potential or perceived vested interests that may have a direct bearing on the subject matter being presented. It is not the intent of this policy to prevent a person with potential vested interests from participating in the planning or presentation of an educational presentation. However, it is imperative that these relationships be identified so that participants may form their own judgments about the presentations.

Such conflict may include, but are not limited to any member who is an owner, employee, consultant, stock or bondholder, lecturer, officer or director for any health related manufacturer, distributor or licensee of products or services associated with gastroenterology, endoscopy or patient care.

These individuals have declared the following:

SPEAKER’S NAME COMPANY

Robert Baldassano Centocor Advisory Board

Anthony Otley Nestle Advisory Board Canada Mead Johnson Speaker’s Bureau Canada

Cynthia King-Moore Nestle Heath Science – Pediatric Expert Panel March 2011

8 Evaluation and Continuing Education Information Sheet APGNN 2011 Annual Meeting: Building A Strong Foundation October 21-22, 2011 in Orlando, FL

IMPORTANT! The online certificate site will be available the end of the day October 22, 2011 through December 2, 2011. After that date, the site will be removed and certificates will no longer be available. If you need a CME / CE certificate, you must complete the evaluation and certificate process prior to that date; otherwise you will forfeit your credit for the course.

To get your certificate, just go to www.CmeCertificateOnline.com.

Scroll down to the APGNN listing and click on the “2011 Annual Meeting: Building A Strong Foundation” event. On the site, you will be asked to enter a password which is BASF2011, select the sessions you attended and evaluate various aspects of the program. You may then print your certificate immediately (encouraged), anywhere you have internet access. No more waiting for the mail! A copy of the certificate will also be emailed to you in case you need to print additional copies (check your spam filter and junk email folder if you do not see it come through). The emailed copy is simply a backup if you didn’t print it right away.

Your hours will be automatically calculated based on the workshops you attend

Please address any questions about the process to: Blia Xiong at [email protected] or 651-789-3719.

Keynote Address

Set for Success

Creating a Strong Foundation in Practice

Danna Cardillo, RN, MA

11 NOTES

12 Set for Success Creating a Strong Foundation in Practice

RN, MA

2011 Cardillo & Associates

"Nursing is a progressive art such that, to stand still, is to go backward." Florence Nightengale

2011 Cardillo & Associates

Professional Associations

•Join

• Get active

•Run for office

• Get on committees

• Develop your skills

2011 Cardillo & Associates

13 Network, Network, Network

• Get yourself out there • Stay in touch • Have business cards made •Start shaking hands • Develop relationships •Making conversation

2011 Cardillo & Associates

Stay Visible at Work

• Get on committees

• Volunteer for special projects

• Toot your own horn

• Participate in social events

2011 Cardillo & Associates

Develop Writing & Speaking Skills

• Take a class

•Read up

•Get some practice

• Seek opportunities

2011 Cardillo & Associates

14 Work on Your Education

• Formal education

• Informal education

• Skill building

• Get to the library

2011 Cardillo & Associates

Master Good Communication Skills

• Use clear, concise language

• Avoid weak phrases

• Ask for what you want

• Learn to take a compliment

• Pay attention to body language/image

2011 Cardillo & Associates

Books, Books, Books

• The ULTIMATE Career Guide for Nurses – by Donna Cardillo, RN • Becoming Influential - A Guide for Nurses – by Eleanor J. Sullivan, RN • Anatomy of Writing for Publication for Nurses – by Cynthia Saver, RN • Presentations for Dummies, 2nd ed. – by M. Kushner • The Quick and Easy Way to Effective Speaking – by Dale Carnegie, Reissue, 1990

2011 Cardillo & Associates

15 Related Articles by Donna

• How to Network Successfully • The Uncommon Handshake • Winning Through Associations • Go Back to School and Change Your Life • Develop the Writer in You • Learn to Speak With Confidence • Conversational Ice Breakers • Six Steps to Getting the Most from Your Job • Master the Scholarship Game Find them at www.dcardillo.com/articles.html

2011 Cardillo & Associates

Contact Donna at 800-801-5796 www.dcardillo.com www.nurse-power.com

2011 Cardillo & Associates

Set for Success Creating a Strong Foundation in Practice

RN, MA

2011 Cardillo & Associates

Don’t Get Stuck in the Gut Rut – Nutrition in the GI Patient

Janelle Peterson, RD, LD, CNSC

17 NOTES

18 Don’t Get Stuck in the Gut Rut

Janelle Peterson, RD, LD, CNSC Pediatric Home Sevice Roseville, MN

Objectives

 Identify ABCs of nutrition assessment

 Identify common nutrition problems with pediatric GI patients

 Gain understanding of nutrition support pearls to use in practice

 Gain knowledge in the assessment of vitamins and minerals

Why is Nutrition Important?

 Disease Prevention

 In our case, prevent co-morbidities and further healthcare issues

 Decrease health care costs

 Formula, feeding tubes, feeding pumps

 Deficiencies, excessive intake

 Prevent long-term health issues

 Bone health, anemia

19 Seeing is Believing

Medical History

 Past Surgeries

 Physical Limitations

 Wheelchair, lying in bed, CP, tone

 Mechanical

 Feeding tube placed

 Central lines

 Pacemakers

 Ostomies

Medical History

 Allergies or Intolerances

 Lab Values

 Hemoglobin, Albumin, Vitamin D

 Tube Site Eval

 How often is it changed, who changes it, care of stoma site

 Dressings used routinely

 Fit of the button or tube anchor

20 Medical History

 Medications

 Routine medications

 Herbal supplements

 Vitamin and Mineral Supplements

 Alternative Medicines

 Fish oil, cod liver oil, Flax Seed Oil

 CoQ10, B Cocktail

 Metagenics

 Special teas

Anthropometrics

 Weight

 Scales used

Weight

 Recumbent scale

 Until they can stand

 Until they no longer fit lengthwise  Stand up scale

 When they can stand

 Adult hold child and weigh  Wheelchair Scale

 Hospitals, clinics

 Expensive

21 Length/Height

 Length

 Until able to stand up tall and straight

 When contractures

 Length mat until over 45 inches

h e

m o s t

p r o m i n e n Length/Heightt p a r t

o f  Height t  Against flat surface h e

o c  On non-carpeted c i p u t floor a n d

j  Use level surface on u s t top of head a b o v e  2 people are best t h e

s u p r a  MCHB modules from University of o r b Washington i t a l

r i d g e

Alternative Height Measures

 Knee height

 www.rxkinetics.com

22 Alternative Height Measures

 Crown Rump Length  Equal to sitting height  Measure from crown to rump with legs at 90 degree angle  Use as pattern measure

 MCHB modules from University of Washington

Alternative Height Measures

 Arm Span  Measure length across arm span from tips of middle fingers

 MCHB modules from University of Washington

Head Circumference = OFC

 MCHB modules from University of  Position the tape just Washington above the eyebrows, above the ears, and around the biggest part on the back of the head

 Pull tape snugly to compress the hair

23 Growth Charts

 Watch trend, not one point in time  For premature infants, chart corrected versus chronological age

 There is a variety  Preterm charts: Babson, Fenton,  Achondroplasia  Cerebral Palsy  CDC  Cornelia De Lange Syndrome  Down Syndrome  Marfan Syndrome

Growth Charts, cont.

 Myelomeningocele  Noonan Syndrome  Prader Willi Syndrome  Sickle Cell Disease  Silver-Russell Syndrome  Turner Syndrome  WHO  Williams Syndrome  Different Cultural growth charts

Charting Growth Charts

 Use corrected age versus chronological

 Use CDC or WHO age-specific growth charts along with disease specific

 Look for trend over time

 Watch for crossing of growth channels

24 Diet History

 Appetite  Ability to Eat/Feeding Skills

 Length of meal

 Food refusal

 Mechanical issues

 Food jags

 Timing of meals

 Grazing or night time eating

Diet History

 Activity

 Bowel habits

 How often

 Consistency

 Bristol Stool card

Diet History

 Diet Restrictions

 Allergies/Intolerances

 GI Symptoms

 Constipation

 Diarrhea

 Abdominal Distention

 Abdominal Cramping

 GER

 When, what, how soon after meals

25 Diet History

 Fluids

 Oral intake

 Water?, Juices?, Gatorade?, Pedialyte?

 Amount given

 How often

 Urine output

Diet History

 Tube Feedings?

 Formula

 Calories per ounce

 Powder

 Liquid concentrate

 Ready-to-feed

 Have them bring a can of formula with

Tube Feedings, cont.

• Continuous

• Rate

• How many hours per day

• Dose

• How much is put in the feeding bag

• Route

• Gtube or jtube

26 Tube Feedings, cont.

 Bolus feedings

 How much per feeding

 How often given

 Use syringe or pump

 Route

 Gtube or Jtube

Tube Feedings, cont.

 Leaking around tube site

 Dressings used

 How does site appear

 Issues for getting formula?

 WIC

 Home Care Agency

 Not covered by insurance

How can the dietitian help?

 Evaluation of formula

 Are fluids being met

 Check for BIG 5 nutrients

 Calcium

 Phosphorous

 Iron

 Vitamin D

 Magnesium

27 How can the dietitian help?

 How are the growth measures trending

 Evaluation of supplements and physician ordered medications

 How can GI symptoms be relieved

 Different formula

 Adding fluids

 Adding fiber

Recommended Texts

 Children with Special Health Care Needs; Nutrition Care Handbook  Pediatric Nutrition Practice Group and Dietetics in Developmental and Psychiatric Disorders of the American Dietetic Association  Handbook of Pediatric Nutrition  Patricia Queen Samour and Kathy King  Pediatric Nutrition in Chronic Diseases and Developmental Disorders  Shirley Ekvall th  Pediatric Nutrition Handbook, 6 edition  American Academy of Pediatrics  Pediatric Nutrition Support  Susan S. Baker, Robert D. Baker, Anne M. Davis

Any Questions?????

Thank you for your time and attention!

Common Uncommon Presentation of Celiac Disease

Ritu Verma, MD

29 NOTES

30 Common Uncommon Presentations of Celiac Disease

Ritu Verma, M.D. Section Chief, Clinical Gastroenterology Division of Gastroenterology and Nutrition The Children’s Hospital of Philadelphia University of Pennsylvania School of Medicine

Objectives

 1. Recognize common and uncommon presentation of Celiac Disease  2. Review diagnostic test for Celiac Disease  3. Discuss the role of genetic testing in Celiac Disease  4. Discuss the management of Celiac Disease

Celiac or Not?

 3 yr old --EB-  Referred by ENT / ALLERGY  Congestion  Cough  Regurgitation  Occasional episodes of abdominal pain

31 Celiac or Not?

 6 YR OLD -AG-  Intermittent abdominal pain  Pain improves with defecation  Alopecia  Alopecia which is worsening  Family history “Gluten sensitivity”

Celiac or Not?

 5 yr old--SG--  PDD diagnosed at 3 yrs age,  Significant behavioral issues  Late walking

Celiac or Not?

 7 year old – BD-  Poor weight gain  Diarrhea- foul smelling stools  Abdominal Distention

32 Celiac or Not?

 13 yr old -MB-  Poor growth  Early Satiety  Constipation  EGD completed

Fantastic Voyage

Celiac Normal

What is Celiac Disease?

Auto-immune condition

Occurs in genetically susceptible individuals

A unique autoimmune disorder because…  Environmental trigger (gluten) and the autoantigen (tissue-transglutaminase) are known  Elimination of the environmental trigger leads to a complete resolution of the disease  Permanent sensitivity to gluten

33 Why is it Important?

 If untreated it poses long-term adverse health consequences including

 Malabsorption  Anemia  Poor growth  Osteopenia  Increased risk of autoimmune conditions  Intestinal lymphoma

Celiac Disease and Autoimmunity

 Prevalence of autoimmune disorders in celiac disease related to duration of gluten exposure

 Diagnosed before 2 years of age: 5%

 Age 2-10 years: 17%

 Greater than age 10 years: 24%

Ventura et al, Gastro 1999; Not , Diabetologia 2001 11

EPIDEMIOLOGY

 Classically occurs in patients of Northern and Western European extraction

 Also reported in Indian, Middle Eastern, Hispanic, and Sudanese patients

 First described in 200 A.D. as a wasting illness

 Gee in the 19th century realized diet was key for treatment

34 Occurrence

 Healthy Population: 1:133  First-Degree Relative 1:18 to 1:22  Second-Degree Relative 1:24 to 1:39  Concordance in monozygotic twins is 70 %  Concordance in HLA identical sibs 30-40% , suggesting other genes involved.  Incidence- Females more than males

Pathogenesis

Genetics Gluten Necessary Causes

Gender Infant feeding Infections Pathogenesis Others ? Microbiom

Risk Factors

Celiac disease

Pathogenesis

 Genetic- multi-factorial, polygenetic  HLA DQ2 and DQ8 are most common factors however not the only  Many non HLA genes have been identified

35 HLA-DQ association with CD

 More than 90% of patients with CD have the DQ2

 8-10% of patients with CD have the DQ8

 Not Diagnostic: Just because you have DQ2 or DQ8 does not mean you have or will have CD. 40% of the population is DQ2+

Other factors

 Clean theory- in developed countries increased incidence of disease  Finland- CD 2X more common than neighbor, Karelia (under developed) with similar genetic makeup  Gut microbata- is different in at risk CD children  Stabilize later in life towards adult microbiom in predisposed children  Phylum Bacteroides absent from GI microbiota up to 24 months in predisposed children

Infant Diet

 Breast feeding should be continued while gluten introduced with slow introduction of gluten  Sweden study- 3% of children diagnosed with CD when food introduction practice changed- stopped breast feeding-late introduction of cereal and baby food had added gluten  Incidence decreased to 1% when cereal introduction at 4-6 months of age with continued breast feeding

36 Infant Diet

 Unanswered Questions  What age should gluten be added to diet?  How much gluten is too much? 1 teaspoon /day to start  Need further studies

Dietary Factors

The Grass Family - (GRAMINEAE) Subfamily Festucoideae

Tribe

Zizaneae Oryzeae Hordeae Aveneae Festuceaea Chlorideae

wild rice rice wheat oat finger millet teff (ragi)

rye

barley

The Celiac Iceberg

Symptomatic Manifest Celiac Disease mucosal lesion

Silent Celiac Disease

Latent Celiac Disease Normal Mucosa

Genetic susceptibility: - DQ2, DQ8 Positive serology

37 Clinical Manifestations

 Gastrointestinal (“classical”)  Non-gastrointestinal ( “atypical”)

 Asymptomatic

Clinical Manifestations

 Gastrointestinal Symptoms (“Classic”)  Chronic or recurrent diarrhea  Abdominal distention  Abdominal pain  Vomiting  Anorexia  Failure to thrive or weight loss  Constipation  Irritability

“Classic” Celiac Disease

The classic presentation:

 Gastrointestinal symptoms starting between 6 and 24 months of age, after the introduction of gluten in the diet.  Infant who has a “potbelly,” wasted extremities, bulky stools, irritability, and laboratory evidence of malabsorption.

38 “Classic” Celiac Disease

Non-Gastrointestinal Manifestations

 Dermatitis Herpetiformis  Elevated transaminases  Dental enamel  Arthritis hypoplasia  Neurological  Osteopenia  Epilepsy  Osteoporosis  Ataxia  Short Stature  Neuropathy  Dementia  Delayed Puberty  Iron Deficiency Anemia  Infertility

Dermatitis Herpetiformis

 Erythematous macule > urticarial papule > tense vesicles

 Severe pruritus

 Symmetric distribution

 90% no GI symptoms

 75% villous atrophy

 Gluten sensitive

Garioch JJ, et al. Br J Dermatol. 1994;131:822-6. Fry L. Baillieres Clin Gastroenterol. 1995;9:371-93. Reunala T, et al. Br J Dermatol. 1997;136-315-8. 27

39 Dental Enamel Defects

Involve the secondary dentition. Commonly seen in third world countries.

Recurrent Aphtous Stomatitis

By permission of C. Mulder, Amsterdam (Netherlands)29

Short Stature/Delayed Puberty

 Short stature in children / teens:  ~10% of short children and teens have evidence of celiac disease

 Delayed menarche:  Higher prevalence in teens with untreated Celiac Disease

40 Liver

 Mild elevation of AST/ALT  Auto-immune Liver disease-PBC>AIH>Sclerosing Cholangitis  Severe liver disease- may require transplant  Interferon therapy for Hepatitis C can exacerbate CD-should screen prior to initiating therapy

Bone Disease in Celiac Disease

 Arthritis  Osteoporosis  Osteopenia  Osteomalacia

 Rickets

Osteoporosis

 Multifactorial  Diet -lactose intolerance  Malabsorption  Antibodies produced that attack a key protein- osteoprotegrin-which is important in maintaining bone health – Vitamin D /Calcium does not help -need Bisphosphonates

41 Neurological and Behavioral Problems

 Zelnick et al. Pediatrics. 2004. 34

Malignancies

 T cell lymphoma

 Prevalence as high as 8%

 With poor adherence to a gluten free diet, pts may have a 40X increased risk of non- Hodgkins lymphoma

MALIGNANCIES

 Increased risk of :

 Adenocarcinoma of small intestine

 Squamous cell Ca of mouth , oropharynx, and esophagus (10X)

 Mortality increased in patients with poor compliance or delay in Dx

42 Asymptomatic

Silent Latent

 Silent: No or minimal symptoms, “damaged” mucosa and positive serology

Identified by screening asymptomatic individuals from groups at risk.

Asymptomatic

 Asymptomatic patients are still at risk of osteopenia/osteoporosis And other autoimmune conditions .  Treatment with a gluten-free diet is recommended for asymptomatic children with proven intestinal changes of Celiac Disease who have:

 Type 1 diabetes – Williams syndrome – Noonan’s syndrome  Selective IgA deficiency – Autoimmune thyroiditis  Down syndrome Down syndrome – a first degree relative with  Turner syndrome Celiac Disease

Increased Incidence

Type 1 Diabetes 10-20% Down syndrome 5% Turner syndrome 5% Williams syndrome 5% Selective IgA deficiency 5% First degree relatives Celiacs 10%

43 Prevalence of Celiac Disease is Higher in Other Autoimmune Conditions

Thyroiditis: 4 - 8% Arthritis: 1.5 - 7.5% Autoimmune liver diseases: 6 - 8% Sjögren’s syndrome: 2 - 15% Idiopathic dilated cardiomyopathy: 5.7% IgA nephropathy: 3.6%.

Asymptomatic

Silent Latent

 Latent: No symptoms, normal mucosa

 May show positive serology. Identified by following in time asymptomatic individuals previously identified at screening from groups at risk. These individuals, given the “right” circumstances, will develop at some point in time mucosal changes (± symptoms)

Diagnosis

44 PLEASE REMEMBER

 DO NOT ALTER DIET UNTIL DIAGNOSIS IS MADE

 Gluten free diet should not be started prior to completion of testing

Serological Tests

Role of serological tests:  Identify symptomatic individuals who need a biopsy  Screening of asymptomatic “at risk” individuals  Supportive evidence for the diagnosis  Monitoring dietary compliance

Serological Tests

 Antigliadin antibodies (AGA)  Deamidated gliadin IGA AND IGG have similar sensitivity and specificity  Anti tissue transglutaminase antibodies (TTG)

 TTG and deamidated gliadin combination gives a higher sensitivity and specificity  Antiendomysial antibodies (EMA)  HLA typing

45 Serum IgA Level

 IgA deficient individuals will have false negative EMA-IgA & TTG-IgA  Check IgA levels with Celiac Disease serology in all individuals  Consider IgG based tests (EMA-IgG & TTG-IgG) in IgA deficiency  Approximately 6 % of Celiac Disease patients have IgA deficiency

Antigliadin Antibodies

 Antibodies (IgG and IgA) to the gluten protein in wheat, rye and barley  May be elevated in SLE and other autoimmune conditions  Advantages  Relatively cheap & easy to perform  Improved sensitivity & specificity in children  Disadvantages  Poor sensitivity and specificity

Deamidated Gliadin Antibody

 Most recent antibody test available.  Based on the conversion of certain gluten peptides to deamidated peptides by the action of intestinal TTG.  Antibody response to deamidated gliadin in patients with Celiac Disease seems to be more intense than the antibody response to native gluten (AGA).  Recent studies have shown that anti-TTG performs better, and it currently is significantly less costly than anti-DGP testing.

46 Tissue Transglutaminase - TTG

 IgA based antibody against tissue transglutaminase (Celiac Disease autoantigen)  Advantages  High sensitivity and specificity (human TTG)  Non operator dependent (ELISA/RIA)  Relatively cheap  Disadvantages  False negative in young children  Only slightly less specific than EMA

Endomysial Antibody - EMA

 Advantages  High sensitivity and specificity  Found in 90-100% of celiac patients  Found in 60-70% of dermatitis herpetiformis patients  Disadvantages  False negatives in young children  Operator dependent  Expensive & time consuming

HLA Tests

 Potential role for DQ2/DQ8 Asymptomatic relatives  Trisomy 21, Turner & Williams syndrome Type 1 diabetes Diagnostic dilemmas TTG +, EMA -, Bx -, Symptoms + ? Prognostic role of DQ2

47 ROLE OF ENDOSCOPY

 To obtain a small intestinal biopsy for histologic analysis to establish the diagnosis of celiac

 Gross endoscopic features include a scalloped appearance to the small bowel

Endoscopic Findings

Scalloping

Normal Appearing Scalloping Nodularity

Marsh Grade

48 Patterns of Mucosal Immunopathology Type 0 Type 1 Type 2 Type 3

Normal Infilitrative Hyper plastic Flat destructive Celiac Diseae Celiac Celiac Celiac (latent) Giardiasis Giardiasis Giardiasis Milk intolerance Milk intolerance Milk intolerance Tropical sprue Tropical sprue Tropical sprue Marasmus Marasmus Marasmus GVHR GVHR GVHR

Marsh, Gastroenterology 1992, Vol 102: 330-35455

Other Endoscopy Techniques

 Enhanced Magnification Endoscopy  Chromoscopic Endoscopy  Magnification Endoscopy with dye spraying  Zoom endoscopy  Optical band imaging  Confocal endomicroscopy

Capsule Endoscopy

 Non invasive  See entire intestinal mucosa  Better sensitivity than standard EGD for detection of severe villous atrophy  Helpful to assess complications of CD  Disadvantage  high cost  lower detection in minor degrees of atrophy  no biopsies

49 Radiology

 CT Enterography  MR Enterography Both evaluate complications

Treatment

 Only treatment for celiac disease is a gluten-free diet (GFD)  Strict, lifelong diet  Avoid:  Wheat  Rye  Barley  Oats

50 Grains to Avoid

Wheat Bulgar Filler Wheat Bran Couscous Graham flour Wheat Starch Durum Kamut Wheat Germ Einkorn Matzo Flour/Meal Barley Emmer Semolina Barley Malt/ Extract Faro Spelt Rye Triticale

Sources of Gluten

 OBVIOUS SOURCES  Bread  Bagels  Cakes  Cereal  Cookies  Pasta / noodles  Pastries / pies  Rolls

Sources of Gluten

POTENTIAL SOURCES – Candy – Communion wafers – Cured Pork Products – Drink mixes – Gravy – Imitation meat / seafood – Sauce – Self-basting turkeys – Soy sauce

51 Ingredients to Question (may contain gluten)

 Seasonings and spice blends or mixes  Modified food starch  Malt/ malt extract/ flavoring  Modified hop extract and yeast-malt sprout extract  Dextrin  Caramel color

Gluten-Free Grains and Starches

• Potato • Millet • Rice • Quinoa • Corn • Amaranth • Teff • Sorghum • Tapioca • Montina • Flax • Arrowroot • Buckwheat • Flours made from nuts, beans and seeds

Safe Ingredients

• Starch • Maltodextrin – Made from cornstarch, potato starch, or rice starch, but not from wheat • Vinegar and Alcohol – Distilled vinegar and distilled spirits are gluten-free, however avoid malt vinegar and malt beverages (e.g. beer)

52 Other Items to Consider

• Lipstick/Gloss/Balms

• Play Dough

• Stamp and Envelope Glues

• Mouthwash/Toothpaste

• Vitamin, Herbal, and Mineral preparations

• Prescription or OTC Medications

Remember

 DIET -life long and avoid cross contamination  study with 50mg gluten daily for 90 days -damage seen Less than 20 mg is recommended

Why is Compliance Important?

 Good evidence to suggest that when children with symptomatic celiac disease adhere to a GFD it results in resolution of GI symptoms, improved growth in height and weight, and normalization of hematological and biochemical parameters (laboratories).  Studies also suggest that the quality of life of children on a GFD who were symptomatic at the time of diagnosis is similar to that of children without celiac disease.  Celiac disease is associated with an overall increased risk of mortality in adults which is primarily the result of GI malignancies. When CD is diagnosed in childhood or adolescence and GFD is initiated, there appears to be no increased cancer risk.

53 Monitoring Treatment

 Periodic visits for assessment of symptoms, growth, and adherence to GFD

 Recommend measurement of antibodies after 6 months of treatment with a GFD

 Routine laboratory evaluation of CBC, CMP, Vitamin D, Hepatitis B status, Thyroid studies, Celiac panel

Compliance can be impaired

 Dietary compliance can be the most difficult aspect of treatment

 Difficulty in obtaining accurate information

 Temptation

 Time and economic constratints

Prevention & Future Directions

54 Celiac Disease-Management: The Future

 Gluten free diet remains best treatment  Refined understanding of “gluten free”  FDA mandates better food labeling  Commercial recognition of the “value” of gluten free products

What is on the Horizon?

 TTG inhibitors -KCC009-Expected to block gluten pepetides  Vaccines-Nexvax2 Gluten peptide and immunotherapy -need multiple doses to induce tolerance -Human trials  Propyl endoprotease -degrades gluten in food matrix in vitro -Human trials

 Larazotide-block zonulin -human trials

Conclusions

 Celiac disease is a common, subtle enteropathy with variable presentation.  Active, appropriate screening is needed to avoid long-term complications of untreated CD.  Family screening initial and follow up  Life long adherence to the diet is important  Dietician involvement  Support groups  Regular follow up with health care team

55 76

Caring for Children Pre and Post Liver Transplantation

Jody Weckwerth, PA-C

57 NOTES

58 Caring for Children Pre and Post Liver Transplantation

Jody Weckwerth, PA-C William J. von Leibig Transplant Center Mayo Clinic Rochester, MN

59 Objectives

1. Identify at least 3 medical issues common to children who are awaiting liver transplantation. 2. List 2-3 side effects of each of the most commonly used post liver transplant immune suppression medications. 3. Recognize medication interactions relevant to children on long term immune suppression.

Disclosures

None

Incidence

 Approx 580 tx per year in US age <18  9% of all liver transplants are in <18 yrs

20%

30%

<1 year 1-5 yrs 13% 6-10 yrs 11-17 yrs

37%

60 Survival Data – Patient

 1 year 85-93%

 3 year 80-87%

 5 year 76-86%

Indications

1. Biliary atresia (41%) 2. Acute liver failure-unknown etiology (11%) 3. Hepatoblastoma (5%) 4. Autoimmune hepatitis 5. Alpha-1 AT deficiency 6. Alagille syndrome Less common: Inborn errors (OTC, GSD, tyrosinemia, etc)

PreTransplant Symptoms

 Ascites 50%  Failure to thrive 47%  Poor concentration, encephalopathy 22%  Portal HTN, GI bleeding 20%  Pruritus 20%  Jaundice  Splenomegaly  Fatigue

61 PreTransplant Issues

 Promote increased liver function  Slow/stop progression of disease  Improve quality of life  Maintain nutrition and growth

PreTransplant Nutrition

 High calorie  Extra vitamins ADEK  Extra MCT  Predigested formula  Measure girth/weight  Use enteral feeds if necessary

Immunizations: Pre-Transplant

Give all usual childhood vaccines Pneumovax MMR Tetanus Varivax Hepatitis A Influenza Hepatitis B Should be given at least 2-4 weeks pretransplant

62 Immune Suppression

 Avoiding rejection vs.

 Proper growth  Avoiding infection

Immune Suppression Regimens  steroid (solumedrol  prednisone or prednisolone)  tacrolimus (Prograf, FK506)  cyclosporine (Neoral)  mycophenolate mofetil (Cellcept)  azathioprine (Imuran)  sirolimus (Rapamune)

63 Side Effects—Calcineurin Inhibitors Mechanism: Inhibits T-lymphocyte activation

 hypertension Tac only  hyperkalemia hyperglycemia  hypomagnesemia lymphoprolif dz  nephrotoxicity CSA only  tremors hirsutism swollen gums

Side Effects—Steroids

. Hypertension . Hyperglycemia . Poor growth . Bone loss, osteopenia . Fluid retention . Mood swings, agitation

Steroids and BMD

 Nightingale et al 2011  52 children aged 4-18  At least 1 year post liver tx  Steroid exposure did not influence BMD  Greater BMD assoc w longer time interval since tx and higher BMI post tx

64 Side Effects—Cellcept Mechanism– inhibits proliferation of T and B lymphocytes

 Abdominal pain  Nausea/vomiting  Diarrhea or constipation  Anemia  Leukopenia  Thrombocytopenia

Side Effects—Sirolimus

 Impaired wound healing  Hyperlipidemia  Rash  Abdominal complaints  Headache

Rejection Treatment

 Pulse IV steroids  Anti-thymocyte globulin  OKT-3 (Inactivates T-cell receptor, prevents T-lymphocyte activation)

↑ Infection risk Anaphylaxis Infusion reactions Pulmonary edema Cerebral edema

65 Medication Interactions Tacrolimus or Cyclosporine Increases drug level Decreases drug level fluconazole phenobarb macrolide abx phenytoin nicardipine, nifedipine rifampin PPI’s metronidazole lovastatin, simvastatin

Typical Scenario

Fluconazole prescribed →→Tac level rises ↓ Fluconazole ends ←← Tac dose decreased ↓ Tac level drops →→ Rejection occurs!!

Head Trouble Off At the Pass

 Have family call before starting any new med prescribed by someone outside of transplant  Provide list of antibiotics that are “OK” without call  Measure drug levels 3-4 days after meds are stopped  Lifelong concern!

66 Post Tx Nutrition

 Cook meats thoroughly  Wash fruits/veg well  Avoid unpasteurized or raw dairy or eggs  Avoid raw fish/shellfish  Caution at buffets or salad bars  Avoid alcohol

Nutrition Concerns Post Tx

 Will take time to recover from pre transplant failure to thrive  Most resume normal diet  Oral aversion may persist  Tube for meds

Immunizations Post-Transplant

. Delay most for 4 months post tx . Do not administer during anti rejection treatment . Avoid live virus vaccines (controversial) Includes MMR, varicella, Flu-mist, Rotarix . Communicate with primary providers

67 Live Virus Vaccines

 An “absolute” contraindication?  Emphasize pre-tx vaccination for seronegative recipients  Beware of “inadvertent” vaccination (pre- employment physicals, etc)

Varicella Vaccine

 A live virus vaccine  2 small series of post tx vaccination  Weinberg (2006) 16 pts, 9 mos-5 yrs post tx (liver or intest) 4 fever, 4 rash; immunity 86% . Khan (2006) 35 ped liver pts, avg 4 yrs post tx 65% immunity; no signif adverse events

MMR Vaccine

 Live virus  Khan (2006) 31 ped liver pts, 3 ½ yrs post tx 73% immunity; Many required 2-3 doses to achieve seroconversion No adverse events reported

68 CDC Vaccination Guidelines

 http://www.cdc.gov/vaccines/spec- grps/conditions.htm

Immunizations- What’s New?

 Influenza All transplant recipients are “high risk” Both patients and household contacts  Rotavirus 2 oral infant vaccines available--RotaTeq and RotaRix (Both are LIVE vaccines)  Meningococcus Use MCV4 (Menactra) age 11-12 or age 2-10 if high risk. Give if MPSV4>3 yrs ago

HPV Vaccine

 Safe and effective  No association w/ death, GBS, or clots  For women ages 9-26  Requires 3 doses at 0, 2, and 6 months  Recommended at age 11-12

69 Post Tx Longterm Follow Up

 Labs every month  Annual: ultrasound, growth, nutrition review, BP  Periodic protocol liver biopsies (e.g. 1, 5, 10 years post tx)  Transition to adult care age 18-22

Other Post Tx Health Concerns  Infection risk

 Sun protection: SPF 30 or higher; protective clothing

 Exercise/Activity

 Obesity risk

70 Post Tx Longterm

 Travel: plan ahead for meds  Pregnancy  Smoking  Alcohol

References 1. Campbell AL, Herold BC. Immunization of pediatric solid-organ transplantation candidates: immunizations in transplant candidates. Pediatr Transplantation 2005;9:652-661. 2. Khan S, et al. Live virus immunization after orthotopic liver transplantation. Pediatr Transpl 2006;10:78-82. 3. Nightingale S, McEwan-Jackson FD, Hawker GA, et al. Corticosteroid exposure not associated with long-term bone mineral density in pediatric liver transplantation. JPGN 2011;53(3): 326-332. 4. Renz JF, de Roos M, Rosenthal P, et al. Posttransplantation growth in pediatric liver recipients. Liver Transpl 2001;7: 1040-1055. 5. Vajdic CM, van Leeuwen MT. Cancer incidence and risk factors after solid organ transplantation. Int J Cancer 2009;125: 1747-1754. 6. Weinberg A, Horslen SP, Kaufman SS, et al. Am J Transpl 2006;6: 565-568. 7. http://optn.transplant.hrsa.gov 8. SPLIT registry data

Multiple Aspects of Inflammatory Bowel Disease

Robert Baldassano, MD

73 NOTES

74 Making Progress… But a Long Way to Go

Experiences with prefrontal lobotomy for intractable ulcerative colitis. JAMA 1956.

What is the role of biologics in the therapy of pediatric IBD?

Robert N. Baldassano, MD

Colman Family Chair in Pediatric IBD Professor of Pediatrics University of Pennsylvania School of Medicine Director, Center for Pediatric IBD The Children's Hospital of Philadelphia

Does 6MP alter the Natural History?

Use of Immunomodulators Intestinal Resection 60 in Different Cohorts 60 in Different Cohorts

P = 0.81 40 40 P < 0.001

20 20 % of Patients % of Patients

0 0 02412 36 48 60 02436486012 Months After Diagnosis Months After Diagnosis 1978-82 1983-87 1988-92 1993-97 1998-2002 No change in operative rates Cosnes J, et al. Gut. 2005;54:237.

75 6-MP: Maintenance Therapy in Children With Crohn’s Disease

1.00

0.75

0.50

Fractional Fractional Survival 6-MP 0.25 Control

0.00 0 100 200 300 400 500 600 Remission Duration (days)

Markowitz J et al. Gastroenterology. 2000;119:895. P=.007

Sans et al, DDW 2011

• RCT involving 268 patients

• After 18 months, the proportion of patients in remission was 67% in the Azathioprine group compared to 57% in the placebo group (p=0.2)

• Azathioprine may not be effective at 18 months

How Effective is Our Current Approach for the Treatment of Pediatric CD? % of Pediatric Patients

Dubner SE et al. Gastro 2009;136:123

76 How Effective is Our Current Approach for the Treatment of Pediatric CD? Z-Scores at Diagnosis, 6 and 12 Months 0.2 Lean Fat Trabecular Height BMI CSMI Mass BMD 0.0 Mass

-0.2

-0.4

-0.6

-0.8

-1.0

-1.2

-1.4 Baseline 6 Months 12 Months Dubner SE et al. Gastro 2009;136:123

Biologic Therapy for Inflammatory Bowel Disease

• Anti-TNF- therapies – Infliximab (FDA approval for Crohn’s disease and Adult UC) – Adalimumab (FDA approval for Adult Crohn’s disease) – Certolizumab (FDA approval for Adult Crohn’s disease)

• Selective adhesion molecules – Natalizumab (FDA limited approval for Crohn’s disease as monotherapy) • Mucosal barrier enhancers – Sargramostim (FDA approval for myeloid recovery after BMT)

Humanization of Anti-TNF agents

Golimumab

Adapted from Rutgeerts Gastro 2009;136:1182

77 †PCDAI score ≤ *Reduction from baseline of RESEAT % change from baseline to 10 weeks REACH REACH that was sustained through 12 months 12 through sustained was that >70%of patients achieved rapid response % of Patients % of Patients Formation during Infliximab Therapy in Infliximab Formation during 10. Improvement in Biomarkers ofBone inBiomarkers Improvement Pediatric Adalimumab Rescue (previously treated with Infliximab) with treated (previously Biomarkers of bone formation andresorption of bone formation Biomarkers P<0.001 ≥ Pediatric InfliximabTrial 15 points in PCDAI score anda PCDAI score n = 99 n =84 n = 66 Pediatric CD P<0.001 n = 33 * n =51 n = 29 ThayuM et al. Clin Gastro Hepa 2008;6(12):1378 = 0.002p = P<0.001 ≤ 30. Hyams et al. Gastroenterology 2007;132:863-87 Rosh, et al. Am J Gastroenterol, 2009 Gastroenterol, J Am al. et Rosh, † 7n= 12 n = 17 n =38 P=0.002 < 0.001p < 3 78 REACH Improvement in Biomarkers of Bone Formation during Infliximab Therapy in Pediatric CD • Conclusions: – Infliximab therapy is associated with:

• dramatic increases in biomarkers (serum BSAP and P1NP) of bone formation – consistent with increase osteoblasts activity – Magnitude of effect (109 %) much greater than that reported in adults (15-18%)

• Significant improvement in height z-score during the 54 week study

Thayu M et al. Clin Gastro Hepa 2008;6(12):1378

REACH Height Velocity: Z-score

Improvements in Bone Density and Dimensions after initiation of Inflixiamb in Pediatric CD Z-Scores at Baseline, and 12 Months (n=24)

Endosteal Circumference Lean Height Trabecular Mass BMD

P<0.001

P=0.002 P=0.01

P=0.004

Thayu M et al. (unpublished data)

79 Early IFX use vs. Traditional Treatment for Pediatric CD

• Retrospective study of 32 children with newly- diagnosed, active ileo-cecal Crohn’s Disease • Group A (IFX) n = 13 – Age range: 5.9-18 years at baseline – IFX schedule: 5 mg/kg at weeks 0, 2, and 6 – 9 also underwent IFX retreatment every 8 weeks for 12 months – All received azathioprine or methotrexate during the IFX infusions and thereafter Romeo E, Gastroenterology. 2006;130 (Suppl II):A56. (preliminary data)

Early IFX use vs. Traditional Treatment for Pediatric CD

• Group B (Traditional treatment ) n = 19 – Age range: 5-17 years at baseline – Corticosteroids: n = 14 – Nutritional course alone: n = 5 – Maintenance therapy with AZA (or MTX)

Romeo E, Gastroenterology. 2006;130 (Suppl II):A56. (preliminary data)

Clinical Relapse During 1-Year Follow-up

12/13* * 17/19 % of Patients

2/19 1/13

Group A (IFX) Group B (Traditional) * P < 0.01 Romeo E, Gastroenterology. 2006;130 (Suppl II):A56.

80 • * Crohn’s Disease Endoscopic Index Severity of Score Infusions

Extension Main • • CDEIS Score 20 25 10 15 0 5 Risks: Benefits: Visits – – – – – Week 54 Week 50 Week 46 Week 42 Week 38 Week 30 Week 26* Week 22 Week 18 Week 14 Week 10 Week 6 Week 2 Week 0* Week Individual and MeanCDEIS Early IFXTherapy forPediatricCD suppression (neoplasms, infections, lymphoma) infections, (neoplasms, suppression immune with long-term ? Safetyconcerns growth Improved healing Better endoscopic Steroid-sparing ofremission maintenance Longer * Endoscopy performed at Weeks 0&26 at Weeks performed * Endoscopy Baseline + placebo infusions at Baseline and 1Year AZA 2.5 mg/kg mg/kg 2.5 AZA n=170 Primary Endpoint (Corticosteroid-free Remission at Week 26) at Week Remission (Corticosteroid-free Endpoint Primary Conclusions ••• ••• ••• ••• ••• • • • p p < 0.01 vs Group B Group vs 0.01 < Baseline vs 0.01 < SONIC Trial Randomization of patients Secondary Endpoint (Week 50) (Week Endpoint Secondary + placebo capsules Infliximab 5mg/kg Infliximab Romeo E, Gastroenterology. 1 Year n=169 • • • Colombel JF et al * Group A(IFX) Group Group B (Traditional) Scores 2006;130 (Suppl II):A56. (Suppl 2006;130 Infliximab 5mg/kg Infliximab + Aza+ 2.5 mg/kg . Eng N JMed 2010 n=169 • • • 81 SONIC Mucosal Healing at Week 26

100

80 p<0.001

p=0.023 p=0.055 60 43.9 40 30.1

20 16.5

Proportion of Patients (%) Patients of Proportion 18/109 28/93 47/107 0

AZA + placebo IFX + placebo IFX+ AZA

Colombel JF et al. N Eng J Med 2010

SONIC Corticosteroid-Free Clinical Remission at Week 50

All Randomized Patients (N=508)* 100

p<0.001 80 p=0.025 p=0.002

60 55.6

39.6 40 28.2 20 Percent of patients (%)

48/170 67/169 94/169 0

AZA + placebo IFX + placebo IFX+ AZA * Patients who did not enter the Study Extension had Week 26 values carried forward Sandborn, WJ et al. DDW 2009.

SONIC Conclusions

• Infliximab/AZA and Infliximab monotherapy were superior to AZA alone

• Infliximab/AZA combination therapy, when started together, was superior to infliximab monotherapy

• Safety was similar in all 3 arms – There was no trend toward an increased risk of serious infections with infliximab

Sandborn , WJ et al. Gastroenterology. 2009; 136 (5): Suppl 1. A-116.

82 Concomitant Immunomodulators with Anti-TNF Agents for Adult CD: One Size Does Not Fit All

Chapter Disease Patient Recommendation extent/behavior characteristics Medication-naive (ie, Limited disease/no Males <26 years, with SONIC population) perianal involvement disease duration >2 years

Extensive/complicated Male <26 years, with disease disease duration ≤2 years

Steroid induced (ie, Limited disease, with or Male or female, any age, COMMIT population) without perianal with no resection involvement Male or female, any age, with ≥1 resection

Failing immunomodulator Limited disease/no Male or female, any age, (ie, starting anti-TNF after perianal involvement with no resection failing IM) Extensive/complicated Male or female, any age, disease extensive resection(s)