Inflectra - Drug Monograph

Introduction

Inflectra (infliximab-dyyb) is a biosimilar medication to Remicade (infliximab), approved by the U.S. Food and Drug Administration (FDA) in 2016. It is a chimeric human-murine monoclonal antibody that specifically binds to tumor necrosis factor-alpha (TNF-α), a key inflammatory mediator. As a biosimilar, Inflectra has demonstrated no clinically meaningful differences from the reference product in terms of safety, purity, and potency.

Mechanism of Action

Inflectra binds with high affinity to both soluble and transmembrane forms of TNF-α, preventing TNF-α from binding to its receptors. TNF-α is a proinflammatory cytokine that plays a central role in the pathogenesis of several immune-mediated inflammatory diseases. By neutralizing TNF-α, Inflectra inhibits:

• Neutrophil chemotaxis and activation
• Expression of adhesion molecules
• Production of proinflammatory cytokines (IL-1, IL-6)
• Induction of acute phase reactants and tissue-degrading enzymes

This results in reduced inflammation and tissue damage in affected organs.

Indications

FDA-approved indications for Inflectra include:

• Rheumatoid arthritis (in combination with methotrexate)
• Crohn's disease in adults and pediatric patients
• Ulcerative colitis in adults and pediatric patients
• Ankylosing spondylitis
• Psoriatic arthritis
• Plaque psoriasis

Dosage and Administration

• Rheumatoid arthritis: 3 mg/kg at 0, 2, and 6 weeks, then every 8 weeks
• Crohn's disease/Ulcerative colitis: 5 mg/kg at 0, 2, and 6 weeks, then every 8 weeks
• Ankylosing spondylitis/Psoriatic arthritis: 5 mg/kg at 0, 2, and 6 weeks, then every 6-8 weeks
• Plaque psoriasis: 5 mg/kg at 0, 2, and 6 weeks, then every 8 weeks

• IV infusion over at least 2 hours
• Must be administered with appropriate medical support for managing hypersensitivity reactions
• Premedication with antihistamines, acetaminophen, and/or corticosteroids may be considered

• Hepatic impairment: No dosage adjustment required
• Renal impairment: No dosage adjustment required
• Elderly: Use with caution due to increased infection risk
• Pediatrics: Dosing based on weight similar to adults

Pharmacokinetics

Contraindications

• Hypersensitivity to infliximab products or any component of the formulation
• Patients with moderate to severe heart failure (NYHA Class III/IV)
• Active tuberculosis or other serious infections
• Concurrent live vaccines

Warnings and Precautions

• Serious infections leading to hospitalization or death
• Tuberculosis reactivation (evaluate and treat latent TB before initiation)
• Invasive fungal infections (histoplasmosis, coccidioidomycosis, blastomycosis)
• Lymphoma and other malignancies

• Hepatitis B virus reactivation
• Hepatotoxicity
• Heart failure exacerbation
• Hematologic abnormalities
• Hypersensitivity reactions (including anaphylaxis)
• Autoimmunity (lupus-like syndrome, autoimmune hepatitis)
• Neurologic events (demyelinating disorders)

Drug Interactions

• Live vaccines: Avoid concurrent administration
• Anakinra: Increased risk of serious infections (avoid combination)
• Abatacept: Increased risk of serious infections (avoid combination)
• Other TNF blockers: Increased risk of adverse events (avoid combination)
• CYP450 substrates: May affect metabolism of drugs metabolized by CYP450 enzymes

Adverse Effects

• Upper respiratory infections
• Headache
• Infusion reactions
• Abdominal pain
• Cough
• Fatigue

• Serious infections (sepsis, pneumonia, opportunistic infections)
• Malignancies (lymphoma, skin cancer)
• Severe hepatic reactions
• Heart failure
• Blood dyscrasias
• Neurologic events
• Severe hypersensitivity reactions

Monitoring Parameters

• Tuberculosis screening (PPD or interferon-gamma release assay)
• Hepatitis B and C serology
• Complete blood count with differential
• Liver function tests
• Renal function
• Pregnancy test if appropriate
• Cardiac assessment in patients with heart failure

• Signs and symptoms of infection at every visit
• CBC, LFTs every 3-6 months
• Periodic skin examination for malignancies
• Monitor for signs of heart failure
• Assess for neurologic symptoms
• Evaluate for autoimmune phenomena

• Monitor for infusion reactions for at least 1-2 hours after administration

Patient Education

• Report any signs of infection (fever, cough, fatigue) immediately
• Notify healthcare provider before receiving any vaccinations
• Seek immediate medical attention for signs of allergic reaction
• Inform all healthcare providers about Inflectra therapy
• Avoid individuals with recent live vaccines
• Report any new or worsening neurological symptoms
• Monitor for signs of heart failure (shortness of breath, swelling)
• Regular skin examinations recommended
• Notify provider if pregnancy is planned or suspected
• Do not discontinue medication without consulting provider

References

1. FDA prescribing information: Inflectra (infliximab-dyyb) 2. Hanauer SB, et al. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet. 2002;359(9317):1541-1549. 3. Rutgeerts P, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353(23):2462-2476. 4. Maini RN, et al. Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthritis Rheum. 1998;41(9):1552-1563. 5. Sands BE, et al. Biosimilars for the treatment of inflammatory bowel disease. Pract Gastroenterol. 2017;41(5):20-33. 6. American Gastroenterological Association Institute Technical Review on the Use of Therapeutic Drug Monitoring of Anti-TNF Agents in Inflammatory Bowel Diseases. Gastroenterology. 2017;153(3):835-857. 7. Singh JA, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2016;68(1):1-26.