Introduction
Yuflyma (adalimumab-aqvh) is a biosimilar to Humira (adalimumab), approved by the FDA in May 2023. It is a tumor necrosis factor (TNF) blocker indicated for multiple autoimmune and inflammatory conditions. As a citrate-free, high-concentration formulation, Yuflyma offers potential administration benefits including reduced injection volume and potentially less injection site discomfort compared to some adalimumab formulations.
Mechanism of Action
Yuflyma binds specifically to tumor necrosis factor-alpha (TNF-α), neutralizing its biological activity by blocking interaction with p55 and p75 cell surface TNF receptors. TNF-α is a naturally occurring cytokine involved in normal inflammatory and immune responses. Elevated levels of TNF-α are found in the synovial fluid of patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, and play a pathogenic role in these conditions as well as in Crohn's disease, ulcerative colitis, and plaque psoriasis. Adalimumab also modulates biological responses that are induced or regulated by TNF-α, including changes in adhesion molecule levels responsible for leukocyte migration.
Indications
Yuflyma is FDA-approved for the following conditions:
- Rheumatoid arthritis (as monotherapy or in combination with methotrexate or other DMARDs)
- Juvenile idiopathic arthritis (in patients 2 years of age and older)
- Psoriatic arthritis
- Ankylosing spondylitis
- Crohn's disease in adults and pediatric patients 6 years and older
- Ulcerative colitis
- Plaque psoriasis in adults and pediatric patients 4 years and older
- Hidradenitis suppurativa
- Uveitis
Dosage and Administration
Standard dosing:- Most indications: 40 mg administered every other week via subcutaneous injection
- Some patients may require 40 mg every week or 80 mg every other week
- Pediatric dosing based on weight for specific indications
- No dosage adjustment needed for elderly patients
- No dosage adjustment needed for patients with renal or hepatic impairment
- Administer subcutaneously in the thigh or abdomen
- Rotate injection sites
- Allow prefilled syringe or pen to reach room temperature (15-30 minutes) before injection
- Citrate-free formulation may reduce injection discomfort
Pharmacokinetics
Absorption: Absolute bioavailability approximately 64% following subcutaneous administration. Maximum serum concentrations reached in 131 ± 56 hours. Distribution: Volume of distribution is 4.7-6.0 L. Binds to TNF-α with high affinity. Metabolism: Cleared via proteolytic enzymes throughout the body. Not primarily metabolized by hepatic cytochrome P450 enzymes. Elimination: Mean terminal half-life is approximately 2 weeks (range 10-20 days). Clearance may be higher in patients with anti-adalimumab antibodies.Contraindications
- Active tuberculosis or other serious infections
- Hypersensitivity to adalimumab or any component of the formulation
- Patients with moderate to severe heart failure (NYHA Class III/IV)
Warnings and Precautions
Serious infections: Increased risk of serious infections leading to hospitalization or death, including tuberculosis, bacterial sepsis, invasive fungal infections, and infections due to opportunistic pathogens. Malignancy: Increased risk of lymphoma and other malignancies, particularly in children and adolescents. Hepatitis B reactivation: Screen patients for HBV infection before initiating treatment. Neurologic events: Rare cases of new onset or exacerbation of demyelinating diseases. Hematologic events: Pancytopenia, including aplastic anemia, has been reported. Heart failure: New onset or worsening of congestive heart failure. Hypersensitivity reactions: Anaphylaxis and angioedema may occur.Drug Interactions
- Anakinra: Increased risk of serious infections and neutropenia
- Abatacept: Increased risk of serious infections
- Live vaccines: Avoid concurrent administration
- CYP450 substrates: May affect formation of CYP450 enzymes
Adverse Effects
Most common (>10%): Injection site reactions, upper respiratory infections, headache, rash, sinusitis Serious adverse effects:- Serious infections (including opportunistic infections)
- Malignancies (including lymphoma)
- Hepatitis B reactivation
- Heart failure
- Hematologic abnormalities
- Hypersensitivity reactions
- Lupus-like syndrome
Monitoring Parameters
- Infection monitoring: Signs and symptoms of infection before, during, and after treatment
- TB screening: Prior to initiation and periodically during therapy
- HBV screening: Prior to initiation
- Liver function tests: Periodically
- Complete blood count: Periodically
- Lipid levels: In patients with psoriasis
- Disease activity: Regular assessment of disease-specific parameters
- Immunogenicity: Development of anti-adalimumab antibodies
Patient Education
- Instruct patients on proper injection technique and site rotation
- Educate about signs and symptoms of infection and when to seek medical attention
- Advise patients to avoid live vaccines during treatment
- Inform patients about potential increased risk of malignancies
- Discuss importance of not stopping concomitant medications unless directed by healthcare provider
- Advise patients to report any new neurological symptoms
- Counsel women of childbearing potential about pregnancy considerations
- Provide instructions for proper storage and handling of medication
References
1. FDA Approval Letter: Yuflyma (adalimumab-aqvh). May 2023. 2. Yuflyma Prescribing Information. Celltrion USA, Inc. 2023. 3. Kay J, et al. Efficacy and safety of high-concentration adalimumab biosimilar. Expert Opin Biol Ther. 2021;21(5):649-657. 4. Smolen JS, et al. EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis. 2020;79(6):685-699. 5. Singh JA, et al. Special Article: 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis. Arthritis Rheumatol. 2019;71(1):5-32. 6. Torres J, et al. ECCO Guidelines on Therapeutics in Crohn's Disease. J Crohns Colitis. 2020;14(1):4-22.