Disclosure 3/10/ NHIA Annual Conference & Exposition 1

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1 Clinical Management of Inflammatory Bowel Disease: Individualizing Treatment Plans with Emerging Biologic Therapies Beth Ann Norton, M.S., R.N., ANP BC Nurse Practitioner and Nursing Program Director Brigham and Women s Hospital Crohn s & Colitis Center Boston, MA Part Time Faculty, Connell School of Nursing Boston College Chestnut Hill, MA Disclosure Beth Ann Norton has received consultant fees from AbbVie and NPS. Clinical trials and off label/investigational uses will not be discussed during this presentation. 2 IBD Basics IBD is a chronic immunologically mediated disease characterized by GI tract inflammation Epidemiology: IBD affects 1.6 million people in the United States Two major forms: Ulcerative colitis and Crohn s disease Age of onset: early childhood to the elderly CD: peak onset years UC: peak onset years Second peak of onset: years (bimodal) Course: Progressive or relapsing/remitting Ananthakrishnan, AK, et al. Inflamm Bowel Dis. 2009:15: ; Cosnes,j, et al. Gastroenterology 2011;140: ; Kornbluth, A., et al. Amer J Gastroenterol. 2010;105: Loftus, EV Jr. Gastroenterology 2004; 126: ; Molodecky NA, 3 et al. Gastroenterology 2012;142: NHIA Annual Conference & Exposition 1

2 4 Pathogenesis of IBD Chronic GI Tract Inflammation Genetic Susceptibility Environmental Triggers Immunologic Factors Abraham C, et al N Engl J Med. 2009;361: ; Ananthakrishnan, AK, et al. Gastroenterol Hepatol 2013;9: ; Khor B, et al. Nature. 2011;474: Infections Environmental Triggers in IBD Antibiotics NSAIDS Diet Stress Smoking NHIA Annual Conference & Exposition 2

3 Clinical Features of IBD Feature Ulcerative colitis Crohn s disease Fever Occasional Common Abdominal pain Varies Common Diarrhea Very common Fairly common Rectal bleeding Very common Fairly common Weight loss Fairly common Common Signs of malnutrition Fairly common Common Perianal disease (fistulae) Absent Fairly common Abdominal mass Absent May occur Growth failure (children and adolescents) Occasional Common Podolsky DK. N Engl J Med. 2002;347: Anatomic Features of IBD (Radiologic and Endoscopic) Feature Ulcerative colitis Crohn s disease Site Large intestine only Mouth to anus Distribution Contiguous mucosal inflammation limited to the lining of the large intestine; typically begins in the rectum and proceeds proximally and may involve the entire colon, left side or rectum only Asymmetric, transmural inflammation affecting any part of the GI tract, but most often the last portion of the ileum and parts of the colon. Presents with skip lesions. Transmural inflammation can lead to perforation/abscesses Ulceration Fine, superficial Deep into submucosa, serpiginous, linear Anal fissures Absent Common Fistulae and Strictures Rare Common Podolsky DK. N Engl J Med. 2002;347: Endoscopic Features in IBD Ulcerative colitis Crohn s disease NHIA Annual Conference & Exposition 3

4 What We Hope to Prevent with Medication GI Cancers and Surgery Image courtesy of Maria Abreu, MD 10 Perianal Crohn s disease Image courtesy of David A. Schwartz, MD 11 Radiological Feature in Crohn s disease Strictures/String sign NHIA Annual Conference & Exposition 4

5 Radiological Feature in Crohn s disease Abscess with free air due to perforation 13 Extraintestinal Manifestations of IBD Inflammatory: Iritis/uveitis Aphthous stomatitis Ankylosing spondylitis/sacroiliitis Peripheral arthralagias Erythema nodosum Pyoderma gangrenosum Primary sclerosing cholangitis Hypercoaguability: DVT/PE Malabsorption: Anemia Cholelethiasis Nephrolethiasis Osteoporosis/Osteopenia Malignancy: Adenocarcinoma of the GI tract Peyrin Biroulet L, et al. Inflamm Bowel Dis. 2011;17: Lichtenstein GR, et al. Am J Gastroenterol. 2009;104: Treatment Goals Short Term Provide rapid and safe relief from symptoms Promote mucosal healing Treat complications Induce remission Long Term Maintain STEROID FREE remission Prevent cancer Prevent complications from medications and IBD Avoid disability and/or lost time from work or school Improve adherence to the medication regimen with regular visits/phone calls/apps Kornbulth A et al. Am J Gastroenterol. 2010;105: ; Lichtenstein G, et al. Am J Gastroenterol 2009;104: NHIA Annual Conference & Exposition 5

6 Aminosalycilates Sulfasalazine Balsalazide Mesalamine Oral (once daily dosing) Topical Corticosteroids Systemic Topical Budesonide 9 mg Medical Treatment Options Ulcerative colitis Thiopurines 6 mercaptopurine Azathioprine Biologics TNF inhibitors Adalimimab Golimumab Infliximab Antigren inhibitor Vedolizumab US Food and Drug Administration. Accessed May 16, 2013; Kornbluth A, et al. Am J Gastroenterol. 2010;105: Aminosalicylates Mesalamine Sulfasalazine Medical Treatment Options Crohn s disease Immunomodulator Methotrexate (sc/po) Antibiotics Ciprofloxacin Metronidazole Cefixime Rifaximin Corticosteroids Systemic Budesonide 3mg Thiopurines 6 mercaptopurine Azathioprine Biologics TNF inhibitors Adalimimab Certolizumab pegol Infliximab Antigren inhibitors Vedolizumab Natalizumab Lichtenstein GR, et al. Am J Gastroenterol. 2009;104: ; Sandborn WJ et al. Am J Gastroenterol. 2012;107:Abstract Traditional Approach Patients have to earn therapy based on severity or failure of other approaches Treatment is based on symptom resolution Evolving Approach Assessment of prognosis Optimization of azathioprine/6 MP (dose or metabolites) Earlier adoption of biologic therapy Appreciation for the implications of healed mucosa Future Approach Individualized therapy based on genetics and physiology Treatment to hard endpoints like mucosal healing or surrogates of it Newer therapies with favorable safety and side effect profiles Appreciation for timing of surgery in the presence of immune suppression 18 Adapted from Hanauer SB. Aliment Pharmacol Ther. 2008;27(Suppl 1): NHIA Annual Conference & Exposition 6

7 Medication Risks TNF Inhibitors Serious infection Lymphoma (NHL) Psoriasis Lupus like reaction Skin cancer (Basal/Squamous) Reactivation of TB Reactivation of HBV Delayed hypersensitivity Thiopurines Serious infection Lymphoma (HSTCL &EBV+) Pancreatitis Liver/bone marrow toxicity MTX Nausea/Vomiting Category X Corticosteroids Serious infection (post op) Bone loss Diabetes Mood swings Adrenal suppression Moon face Acne Natalizumab PML Headache Vedolizumab Headache Nasopharyngitis Arthralgias No live vaccines on immunosuppressive medications 19 Medication Treatment Cases 20 Treatment Case #1 28 year old male with Crohn s ileocolitis since age 15; on Azathioprine 150mg daily Mark and his fiancée come to the office together because she fears he will not give an accurate history and family is concerned about his: Weight loss Fatigue (doesn t go out with friends after work) Inability to get through a meal with out running to the bathroom Post prandial abdominal pain Frequent diarrhea now waking him up at night NHIA Annual Conference & Exposition 7

8 Treatment Case #1 Abnormalities on Exam: RLQ tenderness Tachycardic 8 pound weight loss in 3 months Fever 99.7 p.o. Abnormal Results: ESR 86 (<17) CRP 22 (<8) H/H 8.2 / 24.6 (14/42) Ferritin 8 (30 100) TP 2.8 MRE reveals inflammation in TI and colon 22 Treatment Case #1 Mark refuses to take steroids ever again To temporize and let him consider options for treatment, will Rx: o Cipro 500mg po bid o Metronidazole 250mg po tid with food o Entocort 3mg 3 pills po qam with taper Discuss TNF inhibitors at length Plant a PPD or draw a Quantiferon TB Gold Check for HBV (surface antigen and antibody) Send him home with educational info on Infliximab, Adalimumab and Certolizumab pegol 23 Treatment Case #1 Patient s choice: Adalimumab for ease of administration due to busy life Aza was stopped 3 6 months after starting Adalimumab (risk for HSTCL in young men) One year later, presented with similar s/sx: Adalimumab increased to 40mg SC q week This was an example of Step Up Therapy NHIA Annual Conference & Exposition 8

9 Treatment Case #2 32 year old female with a sibling with UC Joanne quit smoking 6 months ago Taking NSAIDs regularly after joining a gym 3 months ago Well until 4 weeks ago: 4 6 loose stools with some blood Now reports having 15+ bloody stools with urgency and cramping Nocturnal defecation 3 4 times every night Eats and runs to the bathroom so avoids eating (UBW 132 lbs) Stopped exercising because she needs to have urgent diarrhea Bilateral knee arthralgias Fatigued 25 Treatment Case #2 Abnormalities on Exam: LLQ tenderness Tachycardic 5 pound weight loss in 3 4 weeks Treatment: Direct admission to the hospital Colonoscopy scheduled ASAP to r/o IBD Results: ESR 36 (<17) CRP 2 (<8) H/H 10.2 /30.4 (14/42) TP: 3.4 C diff toxin: Negative Colonoscopy stopped at the splenic flexure due to the severity of the disease (continuous from the rectum): Ulcerative colitis 26 Low residue diet Treatment Case #2 IV Solumedrol 20 mg TID Once daily mesalamine (Apriso, Lialda, Asacol HD) TNF Blocker that is on formulary in house: o Adalimumab o Infliximab o Golimumab This is an example of Top Down Therapy NHIA Annual Conference & Exposition 9

10 Parenteral Nutrition in IBD Instead of or in addition to diverting ostomy in Crohn s disease: o For treatment enterocutaneous, severe perianal or rectovaginal fistulas o Along with IR drain(s) and antibiotics for abscess(es) Obstructive episodes due to inflammatory strictures in CD To allow inflammation to lessen prior to starting new medication in those refractory to and/or intolerant of multiple medications in CD Decreased p.o. intake (lessened by 60 80%) High output ostomy or J pouch with evidence of malnutrition Prolonged post op ileus Anastomotic leak post op Malnutrition peri operatively (UC &CD > 25 80% of patients) Short bowel syndrome (long term TPN) Evans JP, et al. J Gastrointest Surg 2003 May Jun;7(4): Parenteral Nutrition in IBD Although significant advances have been made in understanding the pathogenesis, genetics and treatment of IBD, PN is still considered an adjunct therapy Bowel rest: o Decreases antigenicity in bowel lumen d/t decreased ingested proteins o Alters gut microbiota o Decreases colonic fecal bile salt load d/t decreased ingested fats Increased resting energy expenditure during flares Goh, J et al. Aliment Pharmacol Ther 2003; 17: Duerksen,D. MedScape Multidisciplinary 2000; mhttp:// 29 Parenteral Nutrition in IBD Nutritional deficiencies are caused by: o Decreased oral intake o Increased losses (due to underlying diarrhea) o Malabsorption (decreased absorption of vitamin B12 in patients with ileal Crohn s disease or resection or J pouch) Nutrient deficiencies can lead to: o Decreased bone mineral density (decreased Ca++, Vit D) o Thrombophilia (hyperhomocysteinemia 2/2 low folate DVT/PE) o Colon cancer (folate deficiency) o Anemia (iron deficiency, B12 deficiency) Goh, J et al. Aliment Pharmacol Ther 2003; 17: Duerksen,D. MedScape Multidisciplinary 2000; mhttp:// NHIA Annual Conference & Exposition 10

11 Parenteral Nutrition in IBD Glutamine in the PN Formula: A non essential AA preferred as fuel by the small bowel Is an increased requirement in the catabolic state May play a role in decreasing gut permeability and preserving the integrity of gut mucosa Oral glutamine was of no benefit in Crohn s disease Oliveira GP, et al.. An Acad Bras Ciênc. 2010;82(2): Den Hond E, et al. JPEN J Parenter Enteral Nutr. 1999;23:7 11 Goh, J et al. Aliment Pharmacol Ther 2003; 17: TPN Treatment Case 32 TPN as Treatment in IBD Josh is a 27 year old male with Crohn s disease of the terminal ileum (TI) and colon diagnosed in 2008, s/p ICR 2008 Presented with abdominal pain and diarrhea that worsened over 2 months ending in fevers to 101, night sweats, obstructive symptoms, and a 7 # weight loss (69 in., 168# 161#) MRE showed an inflammatory stricture involving a long segment of the neo TI with 3 short skip lesions (~ 22 cm) after losing response to infliximab 10mg/kg q 4 weeks (blood test revealed antibodies to infliximab) MRE also showed a fistula from the small bowel to the sigmoid colon along with an abscess We all wanted to avoid surgery admitted for supportive care, IV antibiotics, and D/C to home on TPN This allowed Josh s gut to cool off ; the abscess and inflammation to decrease or resolve completely, and to allow him to regain some of the weight he lost NHIA Annual Conference & Exposition 11

12 TPN as Treatment in IBD Josh had a very difficult time tolerating TPN emotionally and maintaining a full time work schedule After four weeks on TPN and oral antibiotics, his abscess decreased in size and the long segment of small bowel inflammation decreased as well on repeat MRE He regained 4 pounds At the end of 4 weeks, allowed to try full liquids & soft solid foods He tolerated that so added chicken and fish TPN rate cut down After three days of increased p.o. intake, his TPN was discontinued and his PICC line was pulled 34 TPN at Treatment in IBD 48 hours after Josh s PICC line was pulled, started on a slower than usual loading dose of adalimumab Instead of the traditional 160 mg dose (4 pens) followed by 80 mg (2 pens) two weeks later, Joshua took 2 prefilled pens every 2 weeks xthree to complete the loading dose (then started maintenance dose of one 40 mg pen every 2 weeks) This was done with the hopes of preventing the inflamed TI from healing too quickly and scarring down resulting in a fibrotic stricture We also use a decreased dose of the adalimumab stretched out over a longer interval to prevent a recurrence of the abscess Thankfully this worked out well for Joshua, and his ileal disease went into remission and his abscess did not recur 35 Thank You! NHIA Annual Conference & Exposition 12