Introduction
Hyrimoz (adalimumab-adaz) is a biosimilar to Humira (adalimumab), a tumor necrosis factor-alpha (TNF-α) inhibitor. It is a recombinant human IgG1 monoclonal antibody specifically targeting and neutralizing human TNF-α. Hyrimoz is approved for the treatment of various chronic inflammatory conditions, offering a more accessible treatment option while maintaining comparable efficacy and safety to the reference product.
Mechanism of Action
Hyrimoz binds with high affinity and specificity to soluble and membrane-bound TNF-α, preventing its interaction with p55 and p75 cell surface TNF receptors. By neutralizing TNF-α, a key pro-inflammatory cytokine, Hyrimoz:
- Reduces inflammatory cell migration to sites of inflammation
- Decreases production of other inflammatory mediators (IL-1, IL-6, GM-CSF)
- Modulates cellular adhesion molecules involved in leukocyte migration
- Reduces serum C-reactive protein levels and acute phase reactants
Indications
FDA-approved indications include:
- Rheumatoid arthritis (moderate to severe)
- Psoriatic arthritis
- Ankylosing spondylitis
- Crohn's disease (moderate to severe)
- Ulcerative colitis (moderate to severe)
- Plaque psoriasis (chronic, severe)
- Juvenile idiopathic arthritis (polyarticular, ≥2 years old)
- Hidradenitis suppurativa
- Uveitis (non-infectious intermediate, posterior, and pan-uveitis)
Dosage and Administration
Initial dose: Typically 80 mg subcutaneous injection Maintenance dose: 40 mg every other week (may be increased to 40 mg weekly in some conditions) Special populations:- Pediatric patients: Dose based on body weight (≥15 kg: 20 mg every other week; ≥30 kg: 40 mg every other week)
- Hepatic impairment: No dose adjustment required
- Renal impairment: No dose adjustment required
- Elderly: No dose adjustment required, but increased infection risk
- Administer via subcutaneous injection in thigh or abdomen
- Rotate injection sites
- Allow prefilled syringe/pen to reach room temperature (15-30 minutes) before injection
Pharmacokinetics
Absorption: Bioavailability approximately 64% following subcutaneous administration Distribution: Volume of distribution: 4.7-6.0 L; crosses placenta and present in breast milk Metabolism: Cleared via proteolytic degradation throughout the body Elimination: Half-life approximately 2 weeks (range 10-20 days) Time to peak concentration: 131 ± 56 hours post-dose Steady-state: Achieved in 12-20 weeks with every-other-week dosingContraindications
- Active tuberculosis or other serious infections
- Sepsis or risk of sepsis
- Hypersensitivity to adalimumab or any component formulation
- Moderate to severe heart failure (NYHA Class III/IV)
Warnings and Precautions
Serious infections: Increased risk of bacterial, fungal, viral, and opportunistic infections Malignancy: Increased risk of lymphoma and other malignancies, particularly in children and adolescents Hepatotoxicity: Monitor for liver enzyme elevations and signs of liver injury Hematologic effects: Pancytopenia, aplastic anemia reported Neurologic events: Demyelinating disorders exacerbation risk Heart failure: Worsening or new-onset heart failure possible Autoimmunity: Lupus-like syndrome development possible Vaccinations: Live vaccines should not be administered concurrentlyDrug Interactions
Methotrexate: Reduces adalimumab clearance by approximately 29-44% Other biologics: Increased risk of serious infections; avoid concurrent use Anakinra: Increased risk of serious infections; avoid concurrent use Abatacept: Increased risk of serious infections; avoid concurrent use Live vaccines: Avoid concurrent administration CYP450 substrates: May normalize formation of CYP450 enzymes, affecting drugs metabolized by these enzymesAdverse Effects
Most common (>10%): Injection site reactions (erythema, itching, pain, swelling), upper respiratory infections, headache, rash Serious adverse effects:- Serious infections (sepsis, tuberculosis, invasive fungal infections)
- Malignancies (lymphoma, non-melanoma skin cancer)
- Hepatic failure
- Hematologic disorders
- Heart failure
- Demyelinating disorders
- Lupus-like syndrome
- Hypersensitivity reactions
Monitoring Parameters
Baseline:- Tuberculosis screening (PPD or interferon-gamma release assay)
- Hepatitis B and C screening
- Complete blood count
- Liver function tests
- Renal function
- Pregnancy test if appropriate
- Signs and symptoms of infection at every visit
- CBC and LFTs periodically (every 3-6 months)
- Lipid profile (particularly in psoriasis patients)
- Clinical response assessment
- Injection site reactions
- Signs of malignancy
- Neurologic symptoms
Patient Education
- Report any signs of infection (fever, cough, fatigue) immediately
- Understand proper injection technique and rotation of sites
- Do not receive live vaccines while on therapy
- Report any new neurological symptoms
- Inform all healthcare providers of Hyrimoz use
- Monitor for signs of allergic reactions
- Understand the increased malignancy risk
- Report any unusual bruising or bleeding
- Use sun protection due to increased skin cancer risk
- Notify provider if pregnancy is planned or occurs
References
1. FDA Approval Package: Hyrimoz (adalimumab-adaz). US Food and Drug Administration. 2018. 2. Weinblatt ME, et al. Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum. 2003;48(1):35-45. 3. Hanauer SB, et al. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet. 2002;359(9317):1541-1549. 4. Gordon KB, et al. Adalimumab therapy for moderate to severe psoriasis: A randomized, controlled phase III trial. J Am Acad Dermatol. 2006;54(4):S1-S15. 5. Hyrimoz [package insert]. Princeton, NJ: Sandoz Inc; 2021. 6. Scheinberg MA, et al. Biosimilars: A review of the evidence and clinical applications in rheumatoid arthritis. Autoimmun Rev. 2021;20(5):102789. 7. Singh JA, et al. 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis. Arthritis Rheumatol. 2019;71(1):5-32.