Indications for adalimumab include ankylosing spondylitis, Crohn disease, chronic plaque psoriasis, juvenile idiopathic arthritis, moderate to severe rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis.
Adalimumab-adbm (Cyltezo) is an interchangeable biologic that can serve as a substitute for the originator product, adalimumab (Humira). Its indications include ankylosing spondylitis, Crohn disease, chronic plaque psoriasis, juvenile idiopathic arthritis, moderate to severe rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis.1 The FDA approved adalimumab-adbm on October 15, 2022.2
Mechanism of Action3
Adalimumab-adbm, a recombinant IgG1 monoclonal antibody, is a tumor necrosis factor inhibitor (TNFi). It binds to TNF alpha and blocks the interaction with p55 and p75.
Dosage and Administration4
Juvenile idiopathic arthritis
The manufacturer supplies adalimumab-adbm as a pre-filled syringe to be stored in the refrigerator between 36oF and 46oF. It cannot be frozen. If traveling, patients can store adalimumab-adbm at room temperature up to 77oF for up to 14 days.
The VOLITARE-RA trial found that adalimumab-abdm is a bioequivalent to adalimumab. The 24-week VOLITARE-RA trial randomized 645 patients to be administered 40 mg of adalimumab-abdm or adalimumab. The study used the College of Rheumatology 20% response criteria (ACR 20) required by the FDA and the European Medicines Agency (EMA).
The FDA's asymmetric margin suggests that the difference in ACR29 between adalimumab-abdm and adalimumab must be within -12% and 15% at week 12. The EMA's asymmetric margin suggests that adalimumab-abdm and adalimumab must be within -15% and 15% at week 24.5
At week 12, the ACR associated with adalimumab-abdm was 67% compared to adalimumab's ACR of 61.1%. The ACR results in a 5.9% (95% Cl: -0.9 to 12.7) difference in proportions between the 2 biologics.
At week 24, the ACR of adalimumab-abdm was 69% compared to adalimumab's ACR of 64.5%. The ACR resultsin a 4.5% (95% Cl: -3.4 to 12.5) difference in proportions between the 2 biologics.
The values fall within the range of the FDA and EMA’s asymmetric margin. Adalimumab-abdm and adalimumab are therapeutically equivalent and are biosimilar medications.5
Adverse Events (AEs)
Patients taking adalimumab-abdm are at risk of developing anti-drug antibodies (ADAs) that can neutralize the drug and decrease clinical efficacy. At week 24, 47.4% of adalimumab-abdm patents were ADA-positive compared to 53% of adalimumab-treated patients.5
The most common AEs include injection site pain, headache, and rash.4 Other AEs include serious infections; therefore, patients should not start treatment during an active infection.
Patients are at an increased risk of malignancies and heart failure. Cytopenia may occur, for which patients must stop treatment.4
Warnings and Precautions4
Adalimumab-adbm's boxed warning states that patients are at an increased risk for infections, which can be serious and can result in hospitalization or death. Patients taking concurrent azathioprine or 6-mercaptopurine are at a higher risk of lymphoma.
Previous studies show that adalimumab is actively transported across the placenta by FcRn. Levels range from 4.28 ug/mL to 17.1 ug/mL.6
Adalimumab is actively transported across the placenta during the third trimester and affects the immune response of the infant.4 Prescribers must weigh the benefits and risks of using adalimumab-adbm. Untreated rheumatoid arthritis or irritable bowel disease results in preterm delivery, low birth weight, and low gestational age at birth.4
In studies, the maximum concentration of breast milk in adalimumab was 0.71 mcg/mL and is not associated with any AEs. Adalimumab-adbm should be associated with similar effects on pregnancy and lactation as adalimumab.7
About the Author
Ryan Kurschner is a 2024 PharmD/MPH candidate at the UConn School of Pharmacy.