Module 4 of 14

Biologic Therapy for IBD

2.5 Contact Hours
Level: Intermediate–Advanced
Target: RNs, GI Nurses
ABCGN GI-Specific Credit — Approval Pending

Las Vegas, Nevada

BIOLOGIC THERAPY FOR INFLAMMATORY BOWEL DISEASE:

A COMPREHENSIVE NURSING GUIDE

Clinical Pharmacology, Administration, and Patient Management

Incorporating 2025 AGA and ACG Clinical Practice Guidelines

Target Audience: Registered Nurses, GI/Endoscopy Nurses, Infusion Nurses, Advanced Practice Nurses

Level: Intermediate to Advanced

Release Date: February 2026 | Expiration Date: February 2029

Nevada State Board of Nursing Approved CE Provider

TABLE OF CONTENTS

Disclosures and Course Information

Learning Objectives

Section 1: Inflammatory Bowel Disease Overview

Section 2: Immunology and Mechanism of Action

Section 3: Anti-TNF Biologics

Section 4: Integrin Antagonists

Section 5: Interleukin Inhibitors

Section 6: Janus Kinase (JAK) Inhibitors

Section 7: Pre-Treatment Screening and Monitoring

Section 8: Infusion Administration and Nursing Care

Section 9: Adverse Effects and Safety Monitoring

Section 10: Patient Education and Self-Administration

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References

Course Evaluation

Author Disclosure

The author and planning committee members have no relevant financial relationships with ineligible companies to disclose. All content has been reviewed for bias and clinical accuracy.

Commercial Support

This continuing education activity has received no commercial support.

Off-Label Use Disclosure

This educational activity includes discussion of the following off-label uses:

• Infliximab biosimilars - Some agents may be used interchangeably with reference products

• Certolizumab pegol - Approved for Crohn's disease, used off-label for certain fistulizing phenotypes

• Combination therapy protocols - Certain combinations used in clinical practice

Evidence-Based Guidelines Referenced

This course incorporates the latest evidence-based recommendations from:

• AGA Clinical Practice Guideline on the Management of Moderate to Severe Ulcerative Colitis (2025)

• ACG Clinical Guideline: Management of Crohn's Disease in Adults (2024)

• AGA Technical Review on the Role of Therapeutic Drug Monitoring in IBD (2024)

• ECCO Guidelines on Therapeutics in Inflammatory Bowel Disease (2024)

LEARNING OBJECTIVES

Upon successful completion of this continuing education activity, the participant will be able to:

1. Differentiate between Crohn's disease and ulcerative colitis based on clinical, endoscopic, and histological features

2. Explain the immunological basis of inflammatory bowel disease and how biologic therapies target specific inflammatory pathways

3. Compare mechanisms of action, pharmacokinetics, and clinical indications for anti-TNF agents (infliximab, adalimumab, certolizumab, golimumab)

4. Describe the mechanism and clinical use of integrin antagonists (vedolizumab, natalizumab) including gut-selectivity considerations

5. Summarize the role of interleukin inhibitors (ustekinumab, risankizumab, mirikizumab) in IBD treatment

6. Explain the mechanism and safety considerations for JAK inhibitors (tofacitinib, upadacitinib) as oral advanced therapies

7. Implement pre-treatment screening protocols including tuberculosis testing, hepatitis B status, and vaccination requirements

8. Apply safe infusion administration techniques and monitor for infusion reactions with appropriate management

9. Identify serious adverse effects including infections, malignancy risk, and immunogenicity with appropriate monitoring

10. Develop patient education plans for self-administered biologic therapies including injection technique and storage requirements

SECTION 1: INFLAMMATORY BOWEL DISEASE OVERVIEW

1.1 Definition and Epidemiology

Inflammatory bowel disease (IBD) represents a group of chronic inflammatory conditions of the gastrointestinal tract, with Crohn's disease (CD) and ulcerative colitis (UC) being the two major forms. IBD affects approximately 3 million adults in the United States and carries significant morbidity, healthcare utilization, and impact on quality of life.

Epidemiological Trends:

• Incidence: Rising globally, particularly in newly industrialized countries

• Peak onset: Bimodal distribution (ages 15-30 and 50-70)

• Gender: UC slightly more common in males; CD equal or slightly more common in females

• Geographic variation: Higher rates in North America, Northern Europe, and Israel

• Family history: 10-25% of patients have a first-degree relative with IBD

💡 CLINICAL PEARL: The "hygiene hypothesis" suggests that improved sanitation and reduced childhood infections may contribute to immune dysregulation and IBD development. However, IBD pathogenesis is multifactorial, involving genetic susceptibility, environmental triggers, altered gut microbiome, and immune dysfunction.

1.2 Crohn's Disease

Definition:

Crohn's disease is a chronic, transmural inflammatory condition that can affect any portion of the GI tract from mouth to anus, though the terminal ileum and colon are most commonly involved.

Clinical Features:

Location:

• Ileocolonic (40-50%): Terminal ileum and cecum/ascending colon

• Ileal only (30%): Small bowel predominant

• Colonic only (20%): Colon-limited disease

• Upper GI (5-15%): Esophageal, gastric, or duodenal involvement

Behavior (Montreal Classification):

• Inflammatory (B1): Non-stricturing, non-penetrating

• Stricturing (B2): Luminal narrowing without penetration

• Penetrating (B3): Fistulae, abscesses, or free perforation

• Perianal modifier (+p): Perianal fistulae or abscesses

Characteristic Features:

• Skip lesions (affected areas separated by normal bowel)

• Transmural inflammation (through all bowel layers)

• Non-caseating granulomas (present in 30-50% of biopsies)

• Cobblestoning, aphthous ulcers, longitudinal ulcers

• Fistulae and abscesses

• Strictures and obstruction

Symptoms:

• Abdominal pain (often right lower quadrant)

• Diarrhea (may not be bloody)

• Weight loss and malnutrition

• Fatigue

• Fever (with active inflammation or complications)

• Perianal symptoms (pain, drainage, fissures)

1.3 Ulcerative Colitis

Definition:

Ulcerative colitis is a chronic inflammatory condition limited to the colon, affecting only the mucosa and submucosa, extending proximally from the rectum in a continuous pattern.

Disease Extent (Montreal Classification):

Proctitis (E1):

• Limited to rectum (below rectosigmoid junction)

• May present with tenesmus, urgency, rectal bleeding

Left-Sided Colitis (E2):

• Involvement distal to splenic flexure

• Includes proctosigmoiditis and left-sided disease

Extensive/Pancolitis (E3):

• Extends proximal to splenic flexure

• Highest risk for colorectal cancer surveillance

Clinical Features:

Characteristic Endoscopic Findings:

• Continuous inflammation starting from rectum

• Loss of vascular pattern

• Erythema, friability, granularity

• Erosions and ulcerations

• Pseudopolyps (in chronic disease)

• Clear demarcation between affected and unaffected mucosa

Symptoms:

• Bloody diarrhea (hallmark symptom)

• Rectal urgency and tenesmus

• Fecal incontinence (in severe cases)

• Abdominal cramping

• Fever and tachycardia (in severe flares)

• Weight loss and anemia

⚠️ ALERT - TOXIC MEGACOLON: Acute severe ulcerative colitis can progress to toxic megacolon, characterized by colonic dilation >6 cm on imaging, signs of systemic toxicity, and risk of perforation. This requires immediate hospitalization, bowel rest, IV corticosteroids, and surgical consultation.

1.4 Treatment Goals and Therapeutic Targets

2025 AGA Treatment Targets:

Short-Term Goals (2-4 weeks):

• Symptom improvement

• Reduction in bowel movement frequency

• Control of bleeding (UC)

• Reduction in abdominal pain (CD)

Intermediate Goals (8-12 weeks):

• Clinical remission (resolution of symptoms)

• Normalization of inflammatory markers (CRP, fecal calprotectin)

• Improvement in quality of life

Long-Term Goals (6-12 months and beyond):

• Endoscopic remission/mucosal healing

• Histologic remission (emerging target)

• Prevention of complications (strictures, fistulae, surgery)

• Prevention of colorectal cancer

• Restoration of quality of life

💡 CLINICAL PEARL: Mucosal healing is now a key treatment target in IBD. Patients who achieve mucosal healing have better long-term outcomes including reduced hospitalizations, surgeries, and complications. Symptoms alone do not reliably predict mucosal status—patients may feel well despite ongoing inflammation.

SECTION 2: IMMUNOLOGY AND MECHANISM OF ACTION

2.1 Immune Dysregulation in IBD

Normal Intestinal Immune Function:

The gastrointestinal tract contains the largest immune organ in the body—the gut-associated lymphoid tissue (GALT). Under normal conditions, the intestinal immune system:

• Tolerates commensal bacteria and dietary antigens

• Maintains epithelial barrier function

• Responds appropriately to pathogens

• Limits inflammation after pathogen clearance

IBD Pathogenesis:

In IBD, this delicate balance is disrupted:

1. Genetic Susceptibility:

• Over 200 genetic loci associated with IBD

• NOD2/CARD15 mutations (Crohn's disease)

• IL-23R variants

• Autophagy genes (ATG16L1)

2. Environmental Triggers:

• Smoking (increases CD risk, decreases UC risk)

• Diet (Western diet, processed foods)

• Antibiotics (altered microbiome)

• NSAIDs (mucosal injury)

3. Altered Gut Microbiome:

• Reduced microbial diversity (dysbiosis)

• Decreased beneficial bacteria (Faecalibacterium)

• Increased pathogenic bacteria (Escherichia coli)

4. Epithelial Barrier Dysfunction:

• Increased intestinal permeability ("leaky gut")

• Defective mucus layer

• Impaired antimicrobial peptide production

5. Immune Activation:

• Loss of tolerance to commensal flora

• Excessive cytokine production

• Sustained inflammatory response

2.2 Key Cytokines in IBD

Tumor Necrosis Factor-Alpha (TNF-α):

• Master pro-inflammatory cytokine

• Produced by activated macrophages and T cells

• Promotes inflammation, tissue destruction, and apoptosis

• Target of anti-TNF biologics

Interleukins:

• IL-12 and IL-23: Drive Th1 and Th17 responses

• IL-17: Produced by Th17 cells, promotes neutrophil recruitment

• IL-6: Acute phase response, T cell differentiation

• IL-1β: Inflammasome activation, tissue damage

Interferons:

• IFN-γ: Macrophage activation, barrier dysfunction

2.3 Biologic Targets

Modern biologics target specific components of the inflammatory cascade:

Anti-TNF Agents:

• Neutralize TNF-α, reducing downstream inflammation

• Induce apoptosis of inflammatory cells

• Promote mucosal healing

Integrin Antagonists:

• Block lymphocyte trafficking to the gut

• Prevent inflammatory cell accumulation

• Vedolizumab: Gut-selective (α4β7 integrin)

• Natalizumab: Broader action (α4 integrin)

IL-12/23 Inhibitors:

• Block shared p40 subunit (ustekinumab)

• Reduce Th1 and Th17 responses

IL-23 Inhibitors:

• Selective p19 subunit blockade (risankizumab, mirikizumab)

• Specific targeting of IL-23 pathway

JAK Inhibitors:

• Block intracellular signaling downstream of multiple cytokine receptors

• Oral small molecules (not biologics technically)

• Broad anti-inflammatory effects

SECTION 3: ANTI-TNF BIOLOGICS

3.1 Overview

Anti-TNF agents were the first biologic therapies approved for IBD and remain a cornerstone of treatment. They work by binding to and neutralizing tumor necrosis factor-alpha, a key pro-inflammatory cytokine.

Available Anti-TNF Agents:

Infliximab (Remicade):

• Chimeric (mouse/human) monoclonal antibody

• IV infusion

• First anti-TNF approved for IBD

• Multiple biosimilars available

Adalimumab (Humira):

• Fully human monoclonal antibody

• Subcutaneous injection

• Self-administered

• Multiple biosimilars available

Certolizumab pegol (Cimzia):

• PEGylated Fab fragment

• Subcutaneous injection

• Does not cross placenta (pregnancy considerations)

Golimumab (Simponi):

• Fully human monoclonal antibody

• Subcutaneous injection

• Approved for UC only

3.2 Infliximab

Pharmacology:

• Chimeric (75% human, 25% murine) IgG1 monoclonal antibody

• Binds soluble and transmembrane TNF-α

• Half-life: 7.7-9.5 days

• Distributed primarily in vascular compartment

Indications:

• Moderate-to-severe Crohn's disease

• Moderate-to-severe ulcerative colitis

• Fistulizing Crohn's disease

• Pediatric CD and UC (age ≥6 years)

Dosing:

• Induction: 5 mg/kg IV at weeks 0, 2, and 6

• Maintenance: 5 mg/kg IV every 8 weeks

• Dose escalation: Up to 10 mg/kg or every 4 weeks for loss of response

💡 CLINICAL PEARL: The "therapeutic window" for infliximab trough levels is generally 5-10 mcg/mL for maintenance of remission. Levels below 5 mcg/mL are associated with loss of response, while very high levels do not necessarily provide additional benefit.

Biosimilars:

• Inflectra (infliximab-dyyb)

• Renflexis (infliximab-abda)

• Avsola (infliximab-axxq)

• Ixifi (infliximab-qbtx)

• ZYMFENTRA (infliximab-dyyb - subcutaneous)

3.3 Adalimumab

Pharmacology:

• Fully human IgG1 monoclonal antibody

• Binds soluble and transmembrane TNF-α

• Half-life: ~2 weeks

• Subcutaneous bioavailability: 64%

Indications:

• Moderate-to-severe Crohn's disease

• Moderate-to-severe ulcerative colitis

• Pediatric CD (age ≥6 years)

Dosing:

• Induction: 160 mg SC at week 0, then 80 mg at week 2

• Maintenance: 40 mg SC every 2 weeks

• Some patients may require weekly dosing

Biosimilars:

• Hadlima, Hyrimoz, Cyltezo, Amjevita, Yuflyma, and others

• Multiple options now available

3.4 Certolizumab Pegol

Pharmacology:

• Humanized Fab fragment conjugated to 40 kDa polyethylene glycol

• Lacks Fc region

• Does not cross placenta

• Half-life: ~14 days

Pregnancy Considerations:

Due to lack of Fc region, certolizumab has minimal placental transfer, making it a preferred option for women planning pregnancy or who become pregnant during therapy.

Dosing:

• Induction: 400 mg SC at weeks 0, 2, and 4

• Maintenance: 400 mg SC every 4 weeks

3.5 Golimumab

Pharmacology:

• Fully human IgG1 monoclonal antibody

• Half-life: ~2 weeks

Indications:

• Moderate-to-severe ulcerative colitis (not approved for CD)

Dosing:

• Induction: 200 mg SC at week 0, then 100 mg at week 2

• Maintenance: 100 mg SC every 4 weeks

3.6 Combination Therapy

Rationale:

Combination therapy with an immunomodulator (azathioprine, 6-mercaptopurine, or methotrexate) may improve outcomes by:

• Reducing immunogenicity (anti-drug antibody formation)

• Enhancing drug levels

• Providing synergistic immunosuppression

Evidence:

The SONIC trial demonstrated that infliximab + azathioprine was superior to either agent alone for achieving steroid-free remission in Crohn's disease.

Considerations:

• Increased infection risk

• Increased malignancy risk (hepatosplenic T-cell lymphoma in young males)

• May discontinue immunomodulator after 6-12 months in some patients

SECTION 4: INTEGRIN ANTAGONISTS

4.1 Overview

Integrin antagonists work by blocking lymphocyte trafficking to the intestine, preventing inflammatory cells from accumulating in the gut tissue.

4.2 Vedolizumab (Entyvio)

Mechanism:

• Humanized IgG1 monoclonal antibody

• Selectively blocks α4β7 integrin

• Prevents binding to MAdCAM-1 on intestinal endothelium

• Gut-selective action

Pharmacology:

• Half-life: ~25 days

• Peak serum concentration: 1-8 days after infusion

• Minimal systemic immunosuppression due to gut selectivity

Indications:

• Moderate-to-severe Crohn's disease

• Moderate-to-severe ulcerative colitis

Dosing:

• IV Formulation: 300 mg IV at weeks 0, 2, 6, then every 8 weeks

• SC Formulation: 108 mg SC every 2 weeks (after IV loading)

💡 CLINICAL PEARL: Vedolizumab has a slower onset of action compared to anti-TNF agents (may take 10-14 weeks to see full effect). It is often preferred for patients at higher infection risk or with prior malignancy due to its gut-selective mechanism and favorable safety profile.

Advantages:

• Gut-selective (lower systemic infection risk)

• Good long-term safety profile

• Effective in anti-TNF failures

• No increased malignancy risk observed

• Safe to use with immunomodulators

Considerations:

• Slower onset of action

• May be less effective for fistulizing CD

• Not effective for extraintestinal manifestations

4.3 Natalizumab (Tysabri)

Mechanism:

• Humanized IgG4 monoclonal antibody

• Blocks α4 integrin (α4β1 and α4β7)

• Prevents lymphocyte trafficking to gut AND brain

Black Box Warning - PML:

Natalizumab is associated with progressive multifocal leukoencephalopathy (PML), a rare but potentially fatal brain infection caused by JC virus reactivation. Risk factors include:

• JC virus antibody positivity (especially high index)

• Treatment duration >2 years

• Prior immunosuppressant use

REMS Program:

• Only available through TOUCH Prescribing Program

• Requires JC virus antibody testing

• Regular monitoring and patient education

• Generally reserved for patients who have failed other therapies

Dosing:

• 300 mg IV every 4 weeks

• Must enroll in TOUCH program

SECTION 5: INTERLEUKIN INHIBITORS

5.1 Overview

Interleukin inhibitors target the IL-12/23 or IL-23 pathways, which are central to the Th1 and Th17 immune responses driving IBD inflammation.

5.2 Ustekinumab (Stelara)

Mechanism:

• Fully human IgG1 monoclonal antibody

• Binds p40 subunit shared by IL-12 and IL-23

• Blocks IL-12/23 signaling

• Reduces Th1 and Th17 responses

Pharmacology:

• Half-life: ~3 weeks

• Weight-based IV induction followed by SC maintenance

Indications:

• Moderate-to-severe Crohn's disease

• Moderate-to-severe ulcerative colitis

Dosing:

IV Induction (weight-based):

• ≤55 kg: 260 mg IV

• >55 kg to ≤85 kg: 390 mg IV

• >85 kg: 520 mg IV

SC Maintenance:

• 90 mg SC every 8 weeks (starting 8 weeks after IV induction)

• May shorten to every 4 weeks for inadequate response

💡 CLINICAL PEARL: Ustekinumab has a favorable safety profile with no increased risk of serious infections compared to placebo in clinical trials. It may be particularly useful for patients with concurrent psoriasis or psoriatic arthritis.

5.3 Risankizumab (Skyrizi)

Mechanism:

• Humanized IgG1 monoclonal antibody

• Selectively binds p19 subunit of IL-23

• Blocks IL-23 specifically (not IL-12)

• More targeted approach than ustekinumab

Indications:

• Moderate-to-severe Crohn's disease

• Moderate-to-severe ulcerative colitis (2024 approval)

Dosing:

• Induction: 600 mg IV at weeks 0, 4, and 8

• Maintenance: 360 mg SC every 8 weeks (starting 8 weeks after last IV dose)

5.4 Mirikizumab (Omvoh)

Mechanism:

• Humanized IgG4 monoclonal antibody

• Selectively binds p19 subunit of IL-23

Indications:

• Moderate-to-severe ulcerative colitis

Dosing:

• Induction: 300 mg IV at weeks 0, 4, and 8

• Maintenance: 200 mg SC every 4 weeks (starting 4 weeks after last IV dose)

SECTION 6: JANUS KINASE (JAK) INHIBITORS

6.1 Overview

JAK inhibitors are oral small molecules that block intracellular signaling through the JAK-STAT pathway, which is downstream of multiple cytokine receptors. While technically not "biologics," they are grouped with advanced therapies for IBD.

6.2 Mechanism of Action

JAK Family:

• JAK1, JAK2, JAK3, TYK2

• Different selectivity profiles among agents

• Blocking JAK prevents cytokine signal transduction

Downstream Effects:

• Reduced inflammatory cytokine signaling

• Decreased lymphocyte activation

• Broad anti-inflammatory effect

6.3 Tofacitinib (Xeljanz)

Mechanism:

• Primarily JAK1 and JAK3 inhibitor

• Also affects JAK2

Indications:

• Moderate-to-severe ulcerative colitis

Dosing:

• Induction: 10 mg PO twice daily for 8-16 weeks

• Maintenance: 5 mg PO twice daily (or 10 mg BID if needed)

Black Box Warnings:

• Serious infections (tuberculosis, invasive fungal, opportunistic)

• Mortality

• Malignancies (lymphoma)

• Major adverse cardiovascular events (MACE)

• Thrombosis (DVT, PE)

⚠️ ALERT - SAFETY CONSIDERATIONS FOR JAK INHIBITORS: The FDA has issued warnings regarding increased risk of serious heart-related events, cancer, blood clots, and death with JAK inhibitors, particularly in patients ≥50 years with cardiovascular risk factors. These agents should be used with caution and patients should be counseled about risks.

6.4 Upadacitinib (Rinvoq)

Mechanism:

• Selective JAK1 inhibitor

• More selective than tofacitinib

Indications:

• Moderate-to-severe ulcerative colitis

• Moderate-to-severe Crohn's disease (2023 approval)

Dosing:

Ulcerative Colitis:

• Induction: 45 mg PO once daily for 8 weeks

• Maintenance: 15 mg or 30 mg PO once daily

Crohn's Disease:

• Induction: 45 mg PO once daily for 12 weeks

• Maintenance: 15 mg or 30 mg PO once daily

6.5 JAK Inhibitor Considerations

Advantages:

• Oral administration

• Rapid onset of action

• No immunogenicity

• Short half-life (allows rapid drug clearance if adverse event)

Disadvantages:

• Safety concerns (see black box warnings)

• Twice daily dosing (tofacitinib)

• Multiple drug interactions

• Contraindicated in pregnancy

Laboratory Monitoring:

• Lipid panel (increase in LDL/HDL)

• Complete blood count (lymphopenia, neutropenia, anemia)

• Liver function tests

• Creatine phosphokinase (CPK)

SECTION 7: PRE-TREATMENT SCREENING AND MONITORING

7.1 Pre-Treatment Evaluation

Before initiating biologic therapy, comprehensive screening is essential to identify contraindications and baseline abnormalities.

Required Screening:

Tuberculosis Screening:

• Tuberculin skin test (TST) OR

• Interferon-gamma release assay (IGRA): QuantiFERON-TB Gold or T-SPOT.TB

• Chest X-ray if positive screening test

• Treat latent TB for minimum 1-2 months before starting biologic

Hepatitis B Screening:

• HBsAg (hepatitis B surface antigen)

• Anti-HBc (hepatitis B core antibody)

• Anti-HBs (hepatitis B surface antibody)

• Patients with positive markers: Consult hepatology, consider prophylaxis

Hepatitis C Screening:

• Anti-HCV antibody

• HCV RNA if antibody positive

HIV Screening:

• Recommended for all patients before immunosuppressive therapy

💡 CLINICAL PEARL: IGRA tests are preferred over TST in patients who have received BCG vaccination, as BCG can cause false-positive TST results. However, IGRA results may be indeterminate in immunocompromised patients.

7.2 Vaccination Requirements

Live Vaccines - CONTRAINDICATED during biologic therapy:

• MMR (measles, mumps, rubella)

• Varicella (chickenpox)

• Zoster (live shingles vaccine - Zostavax)

• Rotavirus

• Intranasal influenza (FluMist)

• Yellow fever

• Typhoid (oral)

Complete at least 4 weeks before starting biologic therapy

Non-Live (Inactivated) Vaccines - SAFE during therapy:

• Influenza (injectable)

• Pneumococcal (PCV13, PPSV23)

• Shingrix (recombinant zoster vaccine) - PREFERRED over Zostavax

• Hepatitis A and B

• Tdap

• HPV

• COVID-19 vaccines

• Meningococcal

Recommended Vaccines for IBD Patients:

• Annual influenza

• Pneumococcal vaccination series

• Shingrix (age ≥50 or immunocompromised)

• Hepatitis B series if non-immune

• COVID-19 primary series and boosters

• Tdap booster every 10 years

7.3 Laboratory Monitoring

Baseline Labs:

• Complete blood count with differential

• Comprehensive metabolic panel

• Liver function tests

• C-reactive protein (CRP)

• Fecal calprotectin (if not recently done)

Ongoing Monitoring:

For Anti-TNF Agents:

• CBC and LFTs every 3-6 months

• Consider therapeutic drug monitoring for loss of response

For JAK Inhibitors:

• CBC at baseline, weeks 4-8, then every 3 months

• Lipid panel at 4-8 weeks (and periodically)

• LFTs per prescribing information

• CPK if symptoms of muscle injury

7.4 Therapeutic Drug Monitoring (TDM)

Indications:

• Primary non-response

• Secondary loss of response

• Infusion reactions

• Dose optimization

Components:

• Drug trough level (drawn just before next dose)

• Anti-drug antibody level

Interpretation:

Low Trough, Low/No Antibodies:

• Mechanism issue unlikely

• Consider dose escalation or more frequent dosing

Low Trough, High Antibodies:

• Immunogenicity-driven failure

• Switch within class (if low antibodies) or out of class (if high antibodies)

Adequate Trough, Low/No Antibodies:

• May be mechanistic failure

• Consider switching mechanism of action

💡 CLINICAL PEARL: TDM is proactive when used to optimize dosing before clinical failure occurs. Studies suggest that reactive TDM (after loss of response) may be less effective than proactive optimization.

SECTION 8: INFUSION ADMINISTRATION AND NURSING CARE

8.1 Pre-Infusion Assessment

Patient History:

• Current symptoms and disease activity

• Recent infections (fever, cough, wounds)

• New medications or supplements

• Pregnancy status or plans

• Recent vaccinations

Physical Assessment:

• Vital signs (baseline)

• Assessment for signs of infection

• IV access evaluation

• Previous infusion reaction history

8.2 Infusion Protocols

Infliximab:

Standard Infusion:

• First 3 infusions: Over 2 hours minimum

• If well tolerated: May reduce to 1 hour

• Monitor for minimum 1 hour post-infusion initially

Accelerated Infusion (select patients):

• 1-hour infusion if: No prior reactions AND previous infusions tolerated

• Not recommended for: First 3 infusions, history of reaction, unstable disease

Premedication:

• Not routinely required

• Consider for patients with prior mild reactions

• Options: acetaminophen, diphenhydramine, hydrocortisone

Vedolizumab:

Standard Infusion:

• 300 mg IV over approximately 30 minutes

• Monitor post-infusion as per facility protocol

Ustekinumab:

IV Induction:

• Weight-based dosing (260 mg, 390 mg, or 520 mg)

• Infuse over at least 1 hour

Risankizumab:

IV Induction:

• 600 mg IV over at least 1 hour

• Use 0.2 micron in-line filter

8.3 Infusion Reactions

Types:

Acute Infusion Reactions (during or within 1-2 hours):

• Mild: Flushing, headache, dizziness, nausea

• Moderate: Urticaria, pruritus, dyspnea, chest tightness

• Severe: Anaphylaxis, severe hypotension, bronchospasm

Delayed Reactions (24 hours to 2 weeks):

• Serum sickness-like: Fever, rash, arthralgias, myalgias

Management:

Mild Reactions:

• Slow or temporarily stop infusion

• Administer antihistamine ± acetaminophen

• Resume at slower rate when symptoms resolve

Moderate Reactions:

• Stop infusion

• Administer antihistamine, acetaminophen

• Consider corticosteroids

• May rechallenge at slower rate after resolution

• Have epinephrine available

Severe Reactions:

• Stop infusion immediately

• Initiate anaphylaxis protocol

• Epinephrine IM (0.3-0.5 mg for adults)

• Oxygen, IV fluids, vasopressors as needed

• Do not rechallenge

⚠️ ALERT - ANAPHYLAXIS: Signs include hypotension, severe bronchospasm, laryngeal edema, and loss of consciousness. Time is critical. Administer epinephrine immediately and activate emergency response. Have crash cart available for all infusions.

8.4 Documentation

Required Documentation:

• Pre-infusion assessment

• Medication, dose, lot number, expiration date

• Infusion start and stop times

• Vital signs per protocol

• Any adverse events and interventions

• Patient response and discharge condition

• Patient education provided

SECTION 9: ADVERSE EFFECTS AND SAFETY MONITORING

9.1 Infections

Serious Infections:

All biologics and JAK inhibitors increase infection risk. Serious infections include:

• Bacterial: Pneumonia, cellulitis, sepsis

• Tuberculosis (reactivation of latent TB)

• Fungal: Histoplasmosis, coccidioidomycosis, Pneumocystis

• Viral: Herpes zoster, CMV reactivation

• Opportunistic infections

Risk Factors:

• Advanced age

• Malnutrition

• Diabetes

• Chronic lung disease

• Concurrent corticosteroids or immunomodulators

• Prior serious infections

Monitoring:

• Educate patients to report fever, cough, or infection signs promptly

• Consider holding therapy during active infection

• Annual tuberculosis screening in high-risk patients

• Vaccinations as recommended

9.2 Malignancy

Lymphoma:

• Slightly increased risk with anti-TNF agents

• Higher risk with combination therapy (anti-TNF + thiopurine)

• Hepatosplenic T-cell lymphoma: Rare but often fatal, primarily in young males on combination therapy

Skin Cancer:

• Non-melanoma skin cancer risk increased

• Annual dermatology screening recommended

• Sun protection education

Other Malignancies:

• Overall cancer risk similar to general population

• Caution in patients with recent malignancy

• Generally safe in patients with prior malignancy after appropriate cancer-free interval

9.3 Cardiac Effects (JAK Inhibitors)

Major Adverse Cardiovascular Events (MACE):

• Increased risk with tofacitinib in patients ≥50 with cardiovascular risk factors

• Includes: MI, stroke, cardiovascular death

• Risk-benefit discussion essential

• Avoid in high-risk patients when alternatives exist

9.4 Thromboembolism (JAK Inhibitors)

Increased Risk:

• Deep vein thrombosis (DVT)

• Pulmonary embolism (PE)

• Higher doses associated with higher risk

• Use lowest effective dose for maintenance

Risk Factors:

• Prior VTE

• Surgery

• Immobilization

• Inherited thrombophilia

• Oral contraceptives

• Hormone replacement therapy

9.5 Immunogenicity

Anti-Drug Antibodies (ADA):

• More common with chimeric antibodies (infliximab)

• Reduced with combination immunomodulator therapy

• Can cause: Loss of response, infusion reactions

• Monitor with therapeutic drug monitoring

Strategies to Reduce Immunogenicity:

• Combination therapy with immunomodulator

• Regular maintenance dosing (avoid drug holidays)

• Adequate dosing to maintain therapeutic levels

SECTION 10: PATIENT EDUCATION AND SELF-ADMINISTRATION

10.1 General Patient Education

Disease Understanding:

• Chronic nature of IBD

• Goals of therapy (symptom control, mucosal healing)

• Importance of medication adherence

• Signs of disease flare

Medication Education:

• How the medication works

• Expected timeline for benefit

• Importance of not stopping abruptly

• Need for regular monitoring

Safety Counseling:

• Infection precautions

• When to seek medical attention

• Vaccination recommendations

• Pregnancy and family planning considerations

10.2 Self-Injection Training

Medications:

• Adalimumab

• Certolizumab pegol

• Golimumab

• Ustekinumab (maintenance)

• Vedolizumab SC (after IV induction)

Training Components:

Storage:

• Refrigerate at 36°F-46°F (2°C-8°C)

• Do not freeze

• Protect from light

• Remove from refrigerator 15-30 minutes before injection (allows warming)

• Check expiration date

Injection Sites:

• Abdomen (avoid 2 inches around navel)

• Front of thighs

• Back of upper arms (if caregiver administers)

• Rotate injection sites

Technique:

• Clean hands and injection site with alcohol

• Pinch skin if thin subcutaneous tissue

• Insert needle at 45° or 90° angle depending on device

• Inject medication slowly and completely

• Do not rub injection site after

💡 CLINICAL PEARL: Most self-injectable biologics now come in pre-filled pens or auto-injectors that simplify the injection process. However, pre-filled syringes are available for patients who prefer manual control or who have difficulty with auto-injectors.

10.3 Managing Injection Site Reactions

Common Reactions:

• Redness

• Swelling

• Itching

• Pain or tenderness

Management:

• Apply cold pack before and after injection

• Rotate injection sites

• Allow medication to warm to room temperature

• Consider topical hydrocortisone if persistent

When to Contact Provider:

• Severe pain or swelling

• Signs of infection (warmth, drainage, spreading redness)

• Reactions that worsen with each injection

• Systemic symptoms (fever, hives, difficulty breathing)

10.4 Medication Storage and Travel

At Home:

• Keep in refrigerator (not freezer)

• Store in original packaging to protect from light

• Keep medication organized and check expiration dates

• Know what to do if refrigerator fails

During Travel:

• Use insulated cooler bag with ice packs

• Keep medication in carry-on (do not check)

• Bring letter from healthcare provider

• Know temperature requirements

• Research medication availability at destination

Instructions: Select the best answer for each question. A score of 80% or higher is required to receive CE credit.

1. Which characteristic feature distinguishes Crohn's disease from ulcerative colitis?

A) Bloody diarrhea

B) Transmural inflammation with skip lesions

C) Continuous inflammation from rectum

D) Limited to colon

2. What is the target trough level range for infliximab to maintain remission?

A) 1-3 mcg/mL

B) 5-10 mcg/mL

C) 15-20 mcg/mL

D) 20-30 mcg/mL

3. Which biologic has a gut-selective mechanism that reduces systemic infection risk?

A) Infliximab

B) Adalimumab

C) Vedolizumab

D) Tofacitinib

4. Before initiating anti-TNF therapy, which screening test is required?

A) Colonoscopy

B) Tuberculosis testing

C) Cardiac stress test

D) Pulmonary function test

5. What is the primary reason natalizumab requires a REMS program?

A) Risk of hepatotoxicity

B) Risk of progressive multifocal leukoencephalopathy (PML)

C) Risk of cardiac arrhythmia

D) Risk of pancreatitis

6. Which vaccine is CONTRAINDICATED during biologic therapy?

A) Influenza (injectable)

B) Pneumococcal (PCV13)

C) Varicella (live)

D) Shingrix (recombinant)

7. What is the mechanism of action of JAK inhibitors?

A) Neutralizing TNF-alpha

B) Blocking lymphocyte trafficking

C) Inhibiting intracellular cytokine signaling

D) Binding IL-12/23 p40 subunit

8. For a patient experiencing a moderate infusion reaction to infliximab, what is the appropriate first step?

A) Continue infusion at same rate

B) Administer epinephrine immediately

C) Stop infusion and administer antihistamine

D) Increase infusion rate

9. Which black box warning applies specifically to JAK inhibitors?

A) Progressive multifocal leukoencephalopathy

B) Hepatosplenic T-cell lymphoma

C) Major adverse cardiovascular events (MACE)

D) Lupus-like syndrome

10. What distinguishes certolizumab pegol from other anti-TNF agents regarding pregnancy?

A) It is completely contraindicated in pregnancy

B) It has minimal placental transfer due to lack of Fc region

C) It requires dose doubling during pregnancy

D) It has higher teratogenicity than other agents

11. In therapeutic drug monitoring, low trough levels with high anti-drug antibodies suggest:

A) Need for dose escalation within class

B) Immunogenicity-driven failure requiring class switch

C) Mechanistic failure

D) Adequate therapeutic response

12. What is the primary benefit of the treat-to-target approach in IBD management?

A) Faster symptom relief

B) Lower medication costs

C) Objective monitoring with goal of mucosal healing

D) Simpler dosing regimens

13. Which interleukin inhibitor selectively blocks the p19 subunit of IL-23?

A) Ustekinumab

B) Infliximab

C) Risankizumab

D) Vedolizumab

14. How long should live vaccines be given before starting biologic therapy?

A) At least 2 weeks

B) At least 4 weeks

C) At least 3 months

D) Live vaccines may be given anytime

15. What is the recommended action for a patient on biologics who develops fever and productive cough?

A) Continue therapy and monitor

B) Increase biologic dose

C) Hold therapy and evaluate for infection

D) Switch to a different biologic immediately

16. Which laboratory test is specifically recommended for monitoring patients on JAK inhibitors?

A) Fecal calprotectin monthly

B) Lipid panel at 4-8 weeks

C) Anti-drug antibodies monthly

D) Vitamin B12 levels weekly

17. For self-injectable biologics, how long before injection should medication be removed from refrigerator?

A) Immediately before injection

B) 15-30 minutes before injection

C) 2 hours before injection

D) 24 hours before injection

18. What is the appropriate injection angle for subcutaneous biologic administration?

A) 15 degrees

B) 45 to 90 degrees

C) Exactly 120 degrees

D) Parallel to skin surface

19. Which statement about combination therapy with anti-TNF and immunomodulators is correct?

A) It has no effect on anti-drug antibody formation

B) It reduces immunogenicity but increases infection risk

C) It is never recommended

D) It eliminates the need for therapeutic drug monitoring

20. What is the minimum post-infusion observation period recommended for initial infliximab infusions?

A) 15 minutes

B) 30 minutes

C) 1 hour

D) 2 hours

1. **B) Transmural inflammation with skip lesions**

Rationale: Crohn's disease is characterized by transmural (full-thickness) inflammation and skip lesions (areas of disease separated by normal bowel). Ulcerative colitis affects only the mucosa and submucosa in a continuous pattern from the rectum.

2. **B) 5-10 mcg/mL**

Rationale: Therapeutic drug monitoring studies have established that infliximab trough levels of 5-10 mcg/mL are associated with maintenance of remission. Levels below 5 mcg/mL increase risk of loss of response.

3. **C) Vedolizumab**

Rationale: Vedolizumab selectively blocks α4β7 integrin, which targets the gut-specific MAdCAM-1. This gut-selective mechanism reduces systemic immunosuppression compared to agents with broader mechanisms.

4. **B) Tuberculosis testing**

Rationale: All patients must be screened for latent tuberculosis before starting anti-TNF therapy due to risk of TB reactivation. Testing can be done with TST or IGRA (QuantiFERON or T-SPOT).

5. **B) Risk of progressive multifocal leukoencephalopathy (PML)**

Rationale: Natalizumab carries a risk of PML, a rare but potentially fatal brain infection caused by JC virus reactivation. The TOUCH REMS program requires JC virus antibody testing and patient monitoring.

6. **C) Varicella (live)**

Rationale: Live vaccines are contraindicated during biologic therapy due to risk of vaccine-related infection in immunosuppressed patients. Varicella, MMR, and live zoster (Zostavax) should be given at least 4 weeks before starting biologics.

7. **C) Inhibiting intracellular cytokine signaling**

Rationale: JAK inhibitors block the JAK-STAT pathway, which transmits signals from cytokine receptors inside cells. This is distinct from biologics that work extracellularly.

8. **C) Stop infusion and administer antihistamine**

Rationale: For moderate infusion reactions, the appropriate response is to stop the infusion and administer symptomatic treatment (antihistamine ± acetaminophen, ± corticosteroids). The infusion may be resumed at a slower rate after symptoms resolve.

9. **C) Major adverse cardiovascular events (MACE)**

Rationale: JAK inhibitors carry black box warnings for serious infections, malignancy, MACE, and thromboembolism. The ORAL Surveillance study highlighted increased MACE risk in patients ≥50 with cardiovascular risk factors.

10. **B) It has minimal placental transfer due to lack of Fc region**

Rationale: Certolizumab pegol is a PEGylated Fab fragment that lacks the Fc region responsible for active placental transport of IgG antibodies. This makes it a preferred option during pregnancy.

11. **B) Immunogenicity-driven failure requiring class switch**

Rationale: High anti-drug antibody levels with low trough indicate immunogenicity is clearing the drug. Switching out of class (or within class if antibodies are low) is generally recommended rather than dose escalation.

12. **C) Objective monitoring with goal of mucosal healing**

Rationale: Treat-to-target involves setting specific, measurable goals (including mucosal healing) and adjusting therapy based on objective measures rather than symptoms alone. This approach improves long-term outcomes.

13. **C) Risankizumab**

Rationale: Risankizumab and mirikizumab selectively bind the p19 subunit of IL-23. Ustekinumab binds the p40 subunit shared by IL-12 and IL-23.

14. **B) At least 4 weeks**

Rationale: Live vaccines should be administered at least 4 weeks before initiating biologic or immunosuppressive therapy to allow adequate immune response before immunosuppression begins.

15. **C) Hold therapy and evaluate for infection**

Rationale: Signs of infection warrant holding biologic therapy and prompt medical evaluation. Continuing therapy during active infection increases risk of serious complications.

16. **B) Lipid panel at 4-8 weeks**

Rationale: JAK inhibitors can increase lipid levels (LDL, HDL). A lipid panel should be checked 4-8 weeks after initiation and periodically thereafter. CBC monitoring is also important.

17. **B) 15-30 minutes before injection**

Rationale: Allowing the medication to warm to room temperature (by removing from refrigerator 15-30 minutes before injection) reduces injection site discomfort and is standard practice for self-injectable biologics.

18. **B) 45 to 90 degrees**

Rationale: Subcutaneous injections are given at 45 to 90 degrees depending on the amount of subcutaneous tissue and the device used. Auto-injectors are typically used at 90 degrees.

19. **B) It reduces immunogenicity but increases infection risk**

Rationale: Combination therapy with immunomodulators reduces anti-drug antibody formation (immunogenicity) but increases overall immunosuppression and infection risk. Risk-benefit assessment is required.

20. **C) 1 hour**

Rationale: Patients should be monitored for at least 1 hour after initial infliximab infusions to observe for infusion reactions. Observation time may be reduced for subsequent infusions if prior infusions were well tolerated.

1. Feuerstein JD, et al. AGA Clinical Practice Guideline on the Management of Moderate to Severe Ulcerative Colitis. Gastroenterology. 2025;168(4):577-594.

2. Lichtenstein GR, et al. ACG Clinical Guideline: Management of Crohn's Disease in Adults. Am J Gastroenterol. 2024;119(4):591-636.

3. Vande Casteele N, et al. AGA Technical Review on the Role of Therapeutic Drug Monitoring in the Management of Inflammatory Bowel Disease. Gastroenterology. 2024;166(1):180-200.

4. Torres J, et al. ECCO Guidelines on Therapeutics in Inflammatory Bowel Disease. J Crohns Colitis. 2024;18(3):421-466.

5. Colombel JF, et al. Infliximab, azathioprine, or combination therapy for Crohn's disease (SONIC). N Engl J Med. 2010;362(15):1383-1395.

6. Ytterberg SR, et al. Cardiovascular and Cancer Risk with Tofacitinib in Rheumatoid Arthritis (ORAL Surveillance). N Engl J Med. 2022;386(4):316-326.

7. Mahadevan U, et al. Inflammatory Bowel Disease in Pregnancy Clinical Care Pathway. Gastroenterology. 2019;156(5):1508-1524.

8. Feagan BG, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013;369(8):699-710.

9. Sandborn WJ, et al. Upadacitinib Induction and Maintenance Therapy for Crohn's Disease. N Engl J Med. 2023;389(21):1966-1980.

10. D'Haens G, et al. Risankizumab as induction therapy for Crohn's disease (ADVANCE/MOTIVATE). Lancet. 2022;399(10340):2015-2030.

COURSE EVALUATION

Please complete this evaluation to receive your CE certificate.

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