Therapeutics II: Exam 1 - IBD (UC and CD) RW

What is IBD?

Generic term for series of chronic inflammatory conditions of the GI tract

What 2 conditions are most common with IBD?

Ulcerative Colitis (UC)

Chron's Disease (CD)

At what ages does IBD most commonly occur?

Peaks between ages 14 and 30

In what patients is IBD more common?

More common with European ancestry, white race, and urban dwellers

Occurs in familiar clusters

What is the relationship between NSAIDs and IBD?

NSAIDs can exacerbate IBD

Also a risk factor for development of IBD

What is the relationship between smoking and IBD?

Smoking is a NEGATIVE risk factor for UC

But it INCREASES the severity of CD

What are possible extraintestinal complications of IBD?

Acute arthropathy

Erythema nodosum

Pyoderma gangrenosum

Iritis/uveitis

Ankylosing spondylitis

Primary sclerosing cholangitis

“Metastatic” CD

How are extraintestinal complications of IBD treated?

Treating the luminal disease will usually resolve other problems

Must catch before irreversible damage occurs

What is the general treatment strategy for IBD?

Induction therapy in pt.'s with active disease

Maintenance therapy to prevent recurrence of symptoms

Target therapy to site of disease

How should therapy for IBD be dosed?

"Top Down Approach"

Hit hard with biologics immediately to heal mucosa and trigger remission

MAY be able to taper off over time and achieve long term remission

Continuous treatment with biologics results in better outcomes than episodic treatment

What areas are affected by UC?

Limited to colon and rectum

What causes symptoms in UC?

Shallow ulcers lining continuous sections of the large intestine

What symptoms are seen w/UC?

Chronic loose and bloody stools (hallmark)

Tenesmus

Abd. pain

What is the depth of inflammation in UC?

Superficial

What is described by mild UC?

<4 stools/day

No systemic signs of toxicity

Normal ESR

What is described by moderate UC?

6-10 bloody stools/day

Abdominal pain, but can eat

Positive fecal calprotectin (FCP)

What is described by severe UC?

>10 bloody stools/day

Fever

Tachycardia

Anemia

Positive CRP and FCP

What induction therapy should be used for UC proctitis, of any severity?

5-ASA suppository

What remission therapy should be used for UC proctitis, of any severity?

Continue 5-ASA suppository

If therapy for UC proctitis, of any severity, is not effective what should be used?

Use oral 5-ASA

What induction therapy should be used for UC mild to moderate distal colitis?

5-ASA enema

What remission therapy should be used for UC mild to moderate distal colitis?

Continue 5-ASA enema

If therapy for UC mild to moderate distal colitis, is not effective what should be used?

Use oral 5-ASA

What induction therapy should be used for UC severe distal colitis?

5-ASA Enema

PLUS oral 5-ASA OR budesonide

What remission therapy should be used for UC severe distal colitis?

5-ASA enema PLUS oral 5-ASA

If therapy for UC severe distal colitis, is not effective what should be used?

Treat as pancolitis

Oral 5-ASA or thiopurines for remission

What induction therapy should be used for UC mild to moderate pancolitis?

Oral 5-ASA or Budesonide

What remission therapy should be used for UC mild to moderate pancolitis?

Oral 5-ASA

If therapy for UC mild to moderate pancolitis, is not effective what should be used?

Treat as severe disease

Oral or IV steroids to induce

Thiopurines for remission

What induction therapy should be used for UC severe pancolitis?

Oral or IV steroids

What remission therapy should be used for UC severe pancolitis?

Thiopurines

If therapy for UC severe pancolitis, is not effective what should be used?

Consider early biologics if severe disease on colonoscopy

What induction therapy should be used for UC pancolitis that is not responsive to non-biologic therapy?

Anti-TNF therapy (preferred), or

S1P Modulators, or

IL 12/23 blockers, or

Vedolizumab, or

JAK-inhibitors

What remission therapy should be used for UC pancolitis that is not responsive to non-biologic therapy?

Continue biologic tx.

How does CD manifest?

Focal, asymmetric, transmural, and occasionally granulomatous inflammation affecting the GI tract

What areas are affected by CD?

Can affect ANY part of GI tract (from mouth to anus)

What is the depth of inflammation in CD?

Transmural

What are symptoms of CD?

Diarrhea, usually severe with nocturnal episodes

Abdominal pain and tenderness

Weight loss

Fever

Nausea

Anorexia

What complications are associated with CD?

Ulcers

Fistulas

Abscesses

Intestinal blockage

Extra-intestinal disorders (more common w/CD)

Malnutrition

Growth failure in children

What are fistulas?

Tunnel between 2 sections of intestines, or between intestine and other organs

Very painful

Source of infection

What is described by mild-moderate CD?

Ambulatory patients

Able to tolerate oral feedings

No signs of systemic toxicity

What is described by moderate-severe CD?

Fever,

Weight loss,

Abdominal pain,

Nausea and vomiting, and/or

Significant anemia

What is described by severe-fulminant CD?

Patients with persistent symptoms despite standards induction regimens

Or, those with signs of severe systemic toxicity

What is recommended for induction therapy in mild to moderate CD?

Oral steroids

5-ASA

Enteral nutrition

What is recommended for induction therapy in moderate to severe CD?

Oral steroids

Enteral nutrition

What is recommended for induction therapy in severe to fulminant CD?

IV steroids

IV nutrition

If a patient is steroid refractory, what should be used for CD treatment?

Anti-TNF, Ustekinumab, or Vedolizumab

If a patient is steroid dependent, what should be used for CD treatment?

Thiopurine (AZA or 6-MP); OR

Biologic (Anti-TNF, Ustekinumab, or Vedolizumab)

If a patient is achieves response/remission after induction, what should be used for CD treatment?

Maintain remission

If a patient has perforation, bleeding, obstruction, abscess, refractory lesions, or cancer what should be done for CD treatment?

Surgery

What agents are options for induction of mild to moderate CD?

Mesalamine only if have mild colonic CD

Budesonide

What agents are options for induction of moderate to severe CD?

Oral corticosteroids

Anti-TNF agents (also for maintenance)

Vedolizumab (also for maintenance)

Il 12/23 agents - Ustekinumab (also for maintenance)

Upadacitinib (also for maintenance)

What agents are options for maintenance of moderate to severe CD?

Thiopurines

Methotrexate

Anti-TNF agents (also for induction)

Vedolizumab (also for induction)

Il 12/23 agents - Ustekinumab (also for induction)

Upadacitinib (also for induction)

What agents are options for fistulizing CD?

TNF agents - infliximab, adalimumab, and golimumab

What agents are options for fulminant CD?

IV corticosteroids or TNF agents

What agents are considered for use in pregnancy?

Aminosalicylates

Thiopurines

Biologics (esp. TNFi's)

Induce and maintain remission for 3-6 months before delivery

When are 5-ASA suppositories indicated?

Proctitis treatment

When are 5-ASA enemas indicated?

IBD confined to distal colon

What ADRs are associated with sulfasalazine?

Fever

Rash

Nausea

BMS

What ADRs are associated with mesalamine?

Fewer ADRs than sulfasalazine

Headache, arthralgias, abdominal pain, and nausea can occur

Olsalazine preparation causes more diarrhea

Balsalazide preparation can inc. 6-MP/AZA levels

What is the use of methotrexate in IBD?

Can be used for maintaining remission of CD

What is budesonide?

Corticosteroid

High first-pass effect and low bioavailability

Delivered directly to colon

What is budesonide used for in IBD?

Standard treatment for induction of mild/moderate ileocolonic disease

What is the advantage of using budesonide instead of other oral steroids?

Fewer short-term ADRs than traditional steroids

What are the names of the thiopurines?

6-Mercaptopurine (6-MP)

Azathioprine (AZA)

What are the thiopurines used for in IBD?

Standard agents for maintenance therapy in moderate-to-severe IBD

What is the onset of action of the thiopurines?

Onset of action is usually weeks to 3 months

Often require steroid use short-term

What ADRs are associated with the thiopurines?

Rash

Nausea

Pancreatitis

Diarrhea

Myelosuppression/neutropenia

What monitoring is recommended for the thiopurines?

Monitor the CBC for the first 3 months of treatment, then every 3 months thereafter

Signs of pancreatitis (look for epigastric pain and an increased serum lipase)

What pharmacogenomic testing is recommended for the thiopurines?

TPMT activity

LOW TPMT levels = increased risk for neutropenia

HIGH TPMT levels = decreased efficacy

What are the names of the TNF inhibitors?

Infliximab

Adalimumab

Certolizumab

Golimumab

What is the MOA of the TNF inhibitors?

Block tumor Necrosis Factor-a

Which is responsible for much of the pro-inflammatory response in IBD

Can the TNF inhibitors be used in UC and/or CD?

Both - UC and CD

How are the TNF inhibitors administered?

IV or SubQ

What ADRs/Precautions are associated with the TNF inhibitors?

Infection

Infusion reactions

Autoimmune arthritis

Slight inc. risk lymphoma

When are the TNF inhibitors C/I?

C/I in CHF or autoimmune neurologic conditions

C/I in anyone with an active bacterial infection or in patients with a history of chronic infection

How should patients be screened prior to initiating therapy with TNF inhibitors?

PPD screen for TB

Screening for Hep B/C

Assess vaccination status before starting

What monitoring is recommended for TNF inhibitor therapy?

TDM (drug conc. and anti-drug Ab's)

Signs of infection

What are the names of the α4β7 Integrin Blockers?

Natalizumab

Vedolizumab

What is the MOA of Vedolizumab (α4β7 Integrin Blocker)?

Block inflammatory pathway in gut and brain

What is the main difference between Natalizumab and Vedolizumab?

Natalizumab implicated in reactivating JC virus in brain, causing PML

Vedolizumab does not penetrate BBB

Can the Vedolizumab be used in UC and/or CD?

Both - UC and CD

How is Vedolizumab administered?

SubQ

What ADRs/Precautions are associated with Vedolizumab

Infection

(Does NOT penetrate BBB)

What are the names of the IL-12/23 drugs?

Ustekinumab

Guselkumab

Mirikizumab

Risankizumab

What is the MOA of ustekinumab?

Inhibits IL-12 and IL-23

Key cytokines in the pathogenic immune cascade of CD

Inhibits IL-12 and IL-23-mediated signaling, cellular activation, and downstream cytokine production

When is ustekinumab (Il-12/23) used in IBD?

Induction/maintenance therapy for moderate to severe CD

Usually in patients failing TNF drugs

Can the IL-12/23 drugs (Ustekinumab) be used in UC and/or CD?

Both - UC and CD

How are the IL-12/23 (Ustekinumab) drugs administered?

SubQ

What ADRs/Precautions are associated with the IL-12/23 drugs (Ustekinumab)?

Infection

Hep B increase risk

What are the names of the JAK inhibitors?

Tofacitinib

Upadacitinib

Can the JAK inhibitors be used in UC and/or CD?

Only UC

How are the JAK inhibitors administered?

Oral

What ADRs/Precautions are associated with the JAK inhibitors?

Infection

Shingles reactivation

Increased LDL

When are the JAK inhibitors C/I?

C/I in CAD or pt.'s over 65

What are the names of the S1PR modulators?

Ozanimod

Etrasimod

Can the S1PR modulators (-mod's) be used in UC and/or CD?

Only UC

How are the S1PR modulators (-mod's) administered?

Oral

What ADRs/Precautions are associated with the S1PR modulators (-mod's)?

Bradycardia

Increased LFT's

What treatment(s) has an absolute or relative C/I in pt.'s with latent TB?

Anti-TNF

(can treat TB and then start)