Inflammatory Bowel Disease (IBD) ES

Risk factors for UC

- family hx

- exposure to certain meds

- GI infections

- poor lifestyle habits

- vitamin D deficiency

- concomitant immune mediated diseases

True or false: smoking worsens symptoms of UC

false-- smoking is protective in UC

Risk factors for CD

- family hx

- exposure to certain meds

- GI infections

- poor lifestyle habits

- vitamin D deficiency

- concomitant immune mediated diseases

- smoking

True or false: all of the maintenance and induction meds for IBD are curative

false-- none of them are curative

Corticosteroids in IBD

potent anti-inflammatory effects against T-cells and cytokines

How are corticosteroids used in IBD?

used short term to induce remission and bridge until pt can be put on a long term effective treatment

Why do we prefer budesonide when choosing a corticosteroid for IBD?

it has extensive first pass metabolism, resulting in low systemic bioavailability and potentially less adverse effects

What monitoring parameters do we follow for pts receiving long term corticosteroids for CD?

- bone mineral density

- blood glucose

- lipids

- blood pressure

- eye exam

Immunomodulators purpose in IBD

target immune response or cytokines to control inflammation

Examples of thiopurines

azathioprine, 6-mercaptopurine

MOA: thiopurines

inhibit purine biosynthesis to reduce GI inflammation

Use of thiopurines in IBD

maintains remission

A/E: thiopurines

- myelosuppression

- infections

- pancreatitis

- lymphoma

What should we measure prior to starting a thiopurine?

thiopurine methyltransferase (TPMT) activity measured

Monitoring parameters for thiopurines

- CBC

- CMP

- hepatic function

- renal function

Methotrexate use in IBD

maintains remission in mild CD

A/E: methotrexate

- myelosuppression

- hepatotoxicity

- N/V

- pneumonitis

- renal dysfunction

- anemia

What should we always give with methotrexate?

folic acid

Monitoring parameters for methotrexate

- pregnancy status

- CBC

- CMP

Biologic agent classes for treatment of IBD

TNFis, integrin inhibitors, interleukin inhibitors

Examples of TNFis

infliximab, certolizumab, adalimumab, golimumab

MOA: TNFis

reduce TNFa activity --> decreases inflammatory response

What do we have to screen for before starting a TNFi?

infections (TB, hepatitis)

We should avoid using TNFis in what kind of patients?

patients with advanced or decompensated HF

What trough level do we aim for with infliximab?

10 mcg/ml

Examples of integrin inhibitors

natalizumab, vedolizumab**

MOA: integrin inhibitors

block migration and adhesion of leukocytes across the endothelium

Caution with natalizumab

has a REMs program and is a LAST line treatment

Why do we prefer vedolizumab for integrin inhibitors?

- gut selective

- less systemic immunosuppression and improved safety profile

Examples of interleukin inhibitors

ustekinumab (IL-12/IL-23), risankizumab (IL-23)

MOA: interleukin inhibitors

block IL-12 and IL-23 --> reduces immune response and induction of inflammation

What do we need to screen for before starting a patient on an interleukin inhibitor?

TB and hepatitis

Small molecule drugs for IBD are administered via the ______ route

oral

Examples of JAK inhibitors

tofacitinib (moderate to severe UC only), upadacitinib (moderate to severe UC and CD)

BBW: JAK inhibitors

increased risk for CV events, VTE, malignancies

What do we need to screen patients for before starting them on a JAK inhibitor?

hepatitis and TB

When do we JAK inhibitors in IBD?

patients who have failed or have CIs to TNFis

Examples of sphingosine 1-phosphate (S1P) receptor modulators

ozanimod, etrasimod

What kind of IBD do we use S1Ps for?

moderate to severe UC

MOA: S1P

target S1P receptors to block lymphocytes migration from lymph nodes to GI tract

CI: S1P

pts w/ recent cardiac events in past 6 months

Fistulizing disease in CD

development of abnormal tunnel or connection between two organs or two body structures (ex: tunnel connecting inside of anal canal to an opening in skin near anus)

Treatment of fistulizing disease

- surgery

- can use antibiotics to reduce inflammation (not great research)

- TNFi (Infliximab!)

UC symptoms

- diarrhea (bloody, watery, mucopurulent)

- rectal bleeding

- increased stool frequency

- bowel urgency

- abdominal pain/cramping

- fatigue

- weight loss

- malnutrition

- tenesmus

Tenesmus

feeling of needing to pass stools even though bowels are already empty

UC signs

- tachycardia (with severe disease)

- fever

- dehydration

UC laboratory tests

- leukocytosis

- decreased hematocrit/hemoglobin

- elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP)

- elevated fecal calprotectin

UC differentiation

- continuous, superficial inflammation

- limited to colon and rectum

CD symptoms

- diarrhea (less bloody than UC)

- rectal bleeding (less than UC)

- abdominal pain/cramping

- weight loss and malnutrition (more common than UC)

- fatigue/malaise

CD signs

- fever

- tachycardia

- dehydration

- abdominal mass and tenderness

- perianal fissure, abscess, or fistula

CD laboratory tests

- leukocytosis

- decreased hematocrit/hemoglobin

- elevated ESR/CRP

- hypoalbuminemia with severe disease

- elevated FCP

CD differentiation

- may affect any part of GI tract from mouth to anus

- discontinuous inflammation (patchy, cobblestone)

- transmural inflammation --> penetrates into deep layers of GI tract

Symptomatic control of UC

- oral or topical aminosalicylates

- oral or topical budesonide

- oral prednisone

- rectal steroids

Induction of remission in UC

- oral corticosteroids (budesonide, prednisone)

- TNFi, IL-12/23 inhibitors, integrin inhibitors

ASUC treatment

first line --> IV corticosteroids

second line --> infliximab, cyclosporine, daily JAK inhibitor

Maintenance of remission in UC major point

medications used to successfully induce remission can be continued to maintain remission (except rectal and oral steroids)

What do we do to aminosalicylate dose in mild-moderate UC remission maintenance

drop the dose down for maintenance

Moderate-Severe UC remission maintenance

- biologic or small molecule treatment

- can combine immunomodulators with TNFi

How does mesalamine get to its site of action?

linking to a carrier molecule or altering the formulation to release drug in response to changes in intestinal pH

Carrier molecule for sulfasalazine

sulfapyridine

Issue with sulfasalazine

not tolerated very well due to carrier molecule

A/E: sulfasalazine

- HA

- N/V

- fatigue

- bone marrow suppression

- hepatitis

- pneumonitis

- folate deficiency

Induction of remission in mild-moderate CD

- systemic corticosteroids (budesonide)

- if needed, can add immunomodulators to bridge/overlap

What do we NOT want to use to induce remission in CD

sulfasalazine/mesalamine

Induction of remission in moderate-severe CD

- oral corticosteroids

- biologic or small molecule treatment

- immunomodulator therapy not recommended

Induction of remission in severe-fulminant active disease CD

inpatient IV corticosteroids

Maintenance of remission in CD

- immunomodulators

- biologic or small molecule agents

Things to check before a patient starts a TNFi

- blood tests to rile out TB and viral hepatitis

- clinically significant systemic infections

- existing CIs

- drug interactions