Inflammatory Bowel Disease Flashcards by Carolyn Hardie

Crohns vs Ulcerative colitis location

Crohns: anywhere from mouth to anus

UC: rectum and colon only with possible terminal ileal involvement. No perianal involvement

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Key differences between UC and CD

UC: continuous inflammation; no fistulas/perforations; toxic megacolon possible; no malabsorption; pseudopolyps and risk for colorectal cancer

CD: “cobblestone” appearance (not continuous); fistulas/perforations common; malabsorption & vitamin deficiency common; no pseudopolyps or colon cancer risk

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Severity of UC

range from mild (<=4 stools/day) to fulminant (>10 stools/day with continuous blood)

Fulminant is only severity requiring transfusion

Severe & fulminant will have systemic symptoms of fever, tachycardia, ESR >30

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Severity of CD

Range from mild-mod, mod-severe, severe

severe = no response to steroids, fever, abdominal pain, vomiting - obstruction possible

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Fecal lectoferrin & fecal calprotectin

Elevated in IBD only (not IBS) - so helps differentiate when diagnosing

Can be a guide for treatment efficacy

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IBD adjunctive therapies

Caution use in ACTIVE disease state as these reduce motility and can lead to toxic megacolon (UC)

Imodium
Antispasmodics (dicyclomine, hyoscyamine)
Cholestyramine (if ileal resection)

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Sulfasalazine

Aminosalicylate used for induction & maintenance of IBD

Cleaved by COLONIC bacteria to active form, so efficacy is best in colonic disease

Avoid if sulfa allergy

Titrate from 500-1000mg daily to 3-4g/day due to GI side effects

May cause hepatotoxicity, bone marrow suppression, hemolytic anemia, pancreatitis

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5-Aminosalicylates

First line in mild-moderate UC and CD

Tolerated better compared to sulfasalazine

Nephrotoxicity possible

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Mesalamine forms and site of action

5-aminosalicylate for induction & maintenance

Rowasa= enema = rectum, terminal colon

Delzicol/Asacol/Zaldyon = capsule = distal ileum, colon

Canasa = suppository = rectum

Pentasa = capsule = small bowel, colon

Lialda = tablet = colon

Apriso = capsule = colon

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Olsalazine form and site of action

5-aminosalicylate for induction & maintenance

capsule = colon

Possible secretory diarrhea ADR

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Balsalazide form and site of action

5-aminosalicylate for induction and maintenance

capsule = colon

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Steroids in IBD

Use for flare only - not for maintenance

Adverse effects: adrenal suppressoin, glucose intolerance, hypertension, sodium/water retention, osteoporosis, cataracts, impaired wound healing

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Prednisone to Budesonide for IBD

Requires two week overlap to prevent adrenal insufficiency

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Budesonide indication for IBD

treatment and maintenance of mild-moderate active CD involving **terminal ileum or ascending colon **c

Dosing for CD: 9mg x8 weeks
Maintenance for CD: 6mg x 3 months, then taper

Dosing for Active UC: 9mg daily x8 weeks

works in terminal ileum or ascending colon only

Extensive first pass metabolism; limited systemic exposure

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IV steroids in IBD

flares only

hydrocortisone 100mg q8h or methylprednisolone 15-48mg/day

use for 7-10 days and change to PO when gut functional

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Topical hydrocortisone for IBD

flares only

Use for distal disease
if suppository, use for proctitis

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Topical budesonide for IBD

Induction of remission of mild-moderate distal UC

Uceris rectal foam = 2mg BID x2 weeks then daily x4 weeks

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Immunomodulators for IBD

Mercaptopurine, Azathioprine (prodrug of mercaptopurine), Methotrexate

Indicated for maintenance only (onset = 3-15 months)

MTX = IM weekly for CD only

Azathioprine & mercaptopurine metbolized thru TPMT - check for deficiency before starting

All can cause bone marrow suppression, hepatotoxicity, nausea, diarrhea, rash

A&M: pancreatitis, T-cell lymphoma (in combo w/ TNF blocker)
MTX: pulmonary toxicity, folate deficiency

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Tofacitinib (Xeljanz) for IBD

JAK inhibitor Indicated for mod-severe UC after one or more TNF blocker failure or intolerance

Induction: 10mg BID x8weeks or 22mg ER daily x8 weeks
Maintenance: 5-10mg BID or 11mg ER
D/C if no response at 16 weeks

Dose reduce (10mg BID > 5mg BID or 5mg BID > 5mg daily) IF:
-strong 3A4 & 2C19 inhibitor
-mod-severe renal or hepatic impairment
-ANC 500-1000

D/c if ANC <500

Interrupt if Hgb <8 or serious infection

Upadacitinib (Rinvoq) for IBD

JAK inhibitor Indicated for mod-severe UC after one or more TNF blocker failure or intolerance

Induction: 45mg daily x8 weeks (UC) or 12w (CD)
Maintenance: 15 daily. 30 if severe/refractory
D/C if 30mg ineffective

Adjust to 30mg (induction) or 15mg (maintenance) if:
-CrCl 15-30
-Child Pugh A or B
-Strong 3A4 inhib

Interrupt if severe infection, ANC <1000, lymph <500; Hgb <8

JAK inhibitors class side effects

Serious infections
Lymphocytopenia, neutropenia, low hgb
Lymphoma, lung cancer
Higher rate of MACE
DVT, PE, arterial thrombosis (smokers)
Hepatotoxicity

Update immunizations prior to start of therapy

Ozanimod

Sphingosine 1-phosphate receptor modulator

Oral daily dosing

Indication: mod-severe active UC

Monitor CBC, EKG, LFT, eye exam

Baseline labs for all biologics for IBD

CMP
LFT
CBC
Viral hepatitis
TB

Infliximab (Remicade) IBD

TNF blocker
IV infusion

Indication: induction & maintenance for moderate-severe active UC or CD or fistulizing CD

use in combination with thiopurine

Adalimumab (Humira) IBD

TNF blocker (humanized antibody) SC Indication: induction & maintenance for mod-severe active CD and UC in patients unresponsive to conventional therapy or no longer responding to infliximab Trough > 7 = mucosal healing

Certolizumab (Cimzia) IBD

TNF blocker (humanized MAB) SC week 0, 2, 4 then q4w Indication: maintenance for mod-severe active CD if unresponsive to conventional therapy

Golimumab (simponi) IBD

TNF blocker SC week 0, 2, q4w Indication: mod-severe UC if intolerant of previous therapy or requiring continuous steroids

TNF blocker class adverse effects

Infusion reactions, delayed hypersensitivity (3-10 days after admin) Reactivation of latent infections Heart failure exac (CI in NYHA III/IV) Bone marrow suppression Hepatitis Vasculitis w/ CNS involvement BBW: unusual cancers (hepatosplenic t-cell lymphoma in teenage/young adult males with CD, UC taking infliximab with azatioprine, mercaptopurine)

Natalizumab (tysabri) for IBD

Humanized mab antagonizes integrin heterodimers & inhibits alpha4 integrin-mediated leukocyte adhesion Indication: mod-severe active CD if TNF blockers inadequate Associated with progressive multifocal leukoencephalopathy !!!!! Must enroll in TOUCH program -Monitor mental status changes - if any, consider MRI or LP DC if ineffective after 12 weeks

John Cunningham virus serum antibody test

use for patients on natalizumab (tysabri) before and every 6 months during treatment. D/c if positive

Vedolizumab (Entyvio) for IBD

alpha4B7-integrin-mediated leukocyte target Induction & maintenanace of UC and CD if TNF blockers ineffective More specific for gut-based integrin than natalizumab so less concern for PML D/C if ineffective after 14 weeks

Ustekinumab (Stelara) for IBD

MAB to p40 subunit of IL12 & 23 Indication: mod-severe active CD and UC after failure of steroids, thiopurines, mtx, tnf blockers Weight based induction <55kg = 260mg 55-85kg = 390 >85kg = 520 Maintenance 90mg q8w

Risankizumab (Skyrizi) for IBD

MAB for p19 subunit of IL 23 Indication: mod-severe active CD monitor liver & biirubin

Treatment algorithm for mild UC

1) Topical +/- oral aminosalicylate 2) Budesonide (left-sided) or steroids (any extent) 3) Can do steroid for induction but not remission

Treatment for moderate UC

Budesonide

Treatment for mod-severe UC

1) Steroids or TNF blockers (adalimumab, infliximab, golimumab) 2) Vedolizumab, tofacitinib, ustekinumab

Treatment for hospitalized UC

1) Methylprednisolone 40-60mg daily 2) No response in 3-5 days, then infliximab or cyclosporine

Distal disease in UC

distal to splenic flexure Oral or topical therapy

Extensive disease in UC

proximal to splenic flexure Must use oral therapy

Treatment for mild-moderate CD

ileal, ileocolonic, colonic disease 1) Budesonide (terminal ileal or ascending colonic) 2) aminosalicylate (PO) or metronidazole + ciprofloxacin

Treatment for moderate-severe CD

1) Steroids 2) TNF Blocker + thiopurine 3) If tx failures: infliximab, certolizumab, adalimumab, vedolizumab, ustekinumab, MTX IM or SC

Treatment for severe CD

IF having severe symptoms despite oral steroids or infliximab therapy: Surgery IV steroids TPN IV cyclosporine

Maintenance therapy for CD

-Budesonide up to 3 months -Azathioprine/mercaptopurine +/- infliximab -After surgery: azathioprine/mercaptopurine +/- mesalamine -Infliximab, certolizumab, adalimumab -If failure: vedolizumab, ustekinumab, risankizumab, MTX

Simple perianal disease - CD - treatment

simple fistulas without abscess Metronidazole or cipro Azathioprine/mercaptopurine Infliximab, adalimumab, certolizumab

Complex perianal disease - CD - treatment

Infliximab, adalimumab, certolizumab + surgery ABX: metronidazole OR cipro Azathioprine/mercaptopurine or MTX.