Introduction
Hadlima (biosimilar adalimumab-bwwd) is a tumor necrosis factor (TNF) blocker biosimilar to Humira (adalimumab). It is a recombinant human IgG1 monoclonal antibody specifically binding to human TNF-α, which plays a central role in inflammatory and immune responses. Hadlima was approved by the FDA in July 2019 as the first biosimilar to Humira with an interchangeability designation.
Mechanism of Action
Hadlima binds with high affinity and specificity to soluble and membrane-bound TNF-α, neutralizing its biological activity by blocking interaction with p55 and p75 cell surface TNF receptors. This inhibition of TNF-α activity results in decreased inflammation and modulation of immune responses in various autoimmune conditions. TNF-α is a key inflammatory cytokine involved in the pathogenesis of several chronic inflammatory diseases.
Indications
Hadlima is approved for the following conditions:
- Rheumatoid arthritis (moderate to severe)
- Juvenile idiopathic arthritis (in children 2 years and older)
- Psoriatic arthritis
- Ankylosing spondylitis
- Crohn's disease (moderate to severe)
- Ulcerative colitis (moderate to severe)
- Plaque psoriasis (moderate to severe chronic)
- Hidradenitis suppurativa
- Non-infectious uveitis
Dosage and Administration
Standard dosing:- Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis: 40 mg subcutaneously every other week
- Crohn's disease: Initial dose 160 mg (day 1), 80 mg (day 15), then 40 mg every other week starting day 29
- Ulcerative colitis: Initial dose 160 mg (day 1), 80 mg (day 15), then 40 mg every other week starting day 29
- Plaque psoriasis: Initial dose 80 mg, then 40 mg every other week starting one week after initial dose
- Hepatic impairment: No dosage adjustment needed
- Renal impairment: No dosage adjustment needed
- Elderly: No specific dosage adjustment required
- Pediatrics: Weight-based dosing for juvenile idiopathic arthritis
Pharmacokinetics
Absorption: Bioavailability approximately 64% following subcutaneous administration. Peak serum concentrations reached in 131 ± 56 hours. Distribution: Volume of distribution is 4.7-6.0 L. Crosses placenta and present in breast milk. Metabolism: Degraded via proteolytic enzymes throughout the body. No specific cytochrome P450 involvement. Elimination: Clearance is 12 mL/hour. Half-life is approximately 2 weeks (range 10-20 days). Eliminated primarily via proteolytic catabolism.Contraindications
- Active tuberculosis or other active infections
- History of hypersensitivity to adalimumab or any component of the formulation
- Moderate to severe heart failure (NYHA Class III/IV)
Warnings and Precautions
Boxed Warning:- Serious infections leading to hospitalization or death
- Increased risk of lymphoma and other malignancies
- Hepatitis B virus reactivation
- Increased risk of serious neurological events
- Hypersensitivity reactions including anaphylaxis
- Hematologic events (pancytopenia, aplastic anemia)
- Worsening heart failure
- Autoimmunity (lupus-like syndrome)
- Vaccinations: Live vaccines should not be given concurrently
Drug Interactions
Significant interactions:- Anakinra: Increased risk of serious infections (avoid combination)
- Abatacept: Increased risk of serious infections (avoid combination)
- Other TNF blockers: Increased risk of adverse effects (contraindicated)
- Live vaccines: Potential for disseminated infection (contraindicated)
- CYP450 substrates: May affect metabolism of drugs metabolized by CYP450 enzymes
Adverse Effects
Most common (>10%):- Injection site reactions (erythema, itching, pain, swelling)
- Upper respiratory infections
- Headache
- Rash
- Sinusitis
- Serious infections (sepsis, tuberculosis, invasive fungal infections)
- Malignancies (lymphoma, skin cancer)
- Hepatitis B reactivation
- Heart failure exacerbation
- Demyelinating disorders
- Hematologic events
- 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 applicable
- Signs and symptoms of infection (at each visit)
- CBC and LFTs periodically
- Skin examination for malignancies
- Monitoring for signs of heart failure
- Neurological symptoms
- Therapeutic response assessment
- Annual tuberculosis screening in high-risk patients
- Regular skin cancer screening
- Vaccination status assessment
Patient Education
- Instruct on proper subcutaneous injection technique and rotation of injection sites
- Recognize and report signs of infection (fever, cough, flu-like symptoms)
- Understand increased risk of malignancies and need for regular skin checks
- Avoid live vaccines during treatment
- Report any new neurological symptoms or heart failure symptoms
- Inform all healthcare providers about Hadlima use before any procedures
- Understand importance of not stopping medication abruptly
- Recognize signs of allergic reactions
- Use caution in patients with history of recurrent infections
- Discuss pregnancy planning with healthcare provider
References
1. FDA Approval: Hadlima (adalimumab-bwwd) injection. FDA.gov. 2019 2. Hadlima prescribing information. Samsung Bioepis Co., Ltd. 2023 3. Kay J, et al. Efficacy and safety of biosimilar adalimumab-bwwd in rheumatoid arthritis. Arthritis Rheumatol. 2021 4. Smolen JS, et al. Biosimilars in rheumatology: A review of the evidence for adalimumab biosimilars. Ann Rheum Dis. 2021 5. Cohen SB, et al. Switching from reference adalimumab to biosimilar adalimumab-bwwd in patients with rheumatoid arthritis. Rheumatol Ther. 2022 6. American College of Rheumatology guidelines for the use of biologic therapies. Arthritis Care Res. 2022 7. European Crohn's and Colitis Organisation guidelines on biologic therapy. J Crohns Colitis. 2023 8. National Psoriasis Foundation guidelines on TNF inhibitor therapy. J Am Acad Dermatol. 2021