Inflammatory Bowel Disease Flashcards
Crohns vs Ulcerative colitis location
Crohns: anywhere from mouth to anus
UC: rectum and colon only with possible terminal ileal involvement. No perianal involvement
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
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
Severity of CD
Range from mild-mod, mod-severe, severe
severe = no response to steroids, fever, abdominal pain, vomiting - obstruction possible
Fecal lectoferrin & fecal calprotectin
Elevated in IBD only (not IBS) - so helps differentiate when diagnosing
Can be a guide for treatment efficacy
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)
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
5-Aminosalicylates
First line in mild-moderate UC and CD
Tolerated better compared to sulfasalazine
Nephrotoxicity possible
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
Olsalazine form and site of action
5-aminosalicylate for induction & maintenance
capsule = colon
Possible secretory diarrhea ADR
Balsalazide form and site of action
5-aminosalicylate for induction and maintenance
capsule = colon
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
Prednisone to Budesonide for IBD
Requires two week overlap to prevent adrenal insufficiency
Budesonide indication for IBD
flares only
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
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
Topical hydrocortisone for IBD
flares only
Use for distal disease
if suppository, use for proctitis
Topical budesonide for IBD
Induction of remission of mild-moderate distal UC
Uceris rectal foam = 2mg BID x2 weeks then daily x4 weeks
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
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.
