Relevance of Adalimumab Product Attributes to Patient Experience in the Biosimilar Era: A Narrative Review

Adalimumab (ADL, Humira^®, reference product), an anti-TNF-α biologic, has transformed the treatment of chronic, immune-mediated inflammatory diseases. However, the high cost of ADL therapy has driven the development of more affordable ADL biosimilars, agents with no clinically meaningful differences from the reference product. This review summarizes the product attributes of reference ADL and the nine ADL biosimilars approved and available in the USA in relation to patient experience of injection-site pain (ISP). Product formulation, delivery volume and device features (e.g., type and needle gauge size) influence patient experience of ISP with potential clinical consequences. Citrate-free formulations generally cause less ISP; injection volumes of > 1.5 ml may be associated with increased ISP. Reference ADL and all ADL biosimilars offer a citrate-free formulation, and reference ADL and four ADL biosimilars offer a high-concentration solution that allows a smaller injection volume. All available ADL products are injected subcutaneously using either a pre-filled pen (PFP) or pre-filled syringe (PFS). Patients prefer the PFP, but the PFS permits better control over the speed and duration of injection. Smaller (29-gauge) needle outer diameter is associated with less ISP; reference ADL and seven ADL biosimilars offer a device with a 29-gauge needle. In the USA, an approved biosimilar can be designated "interchangeable," allowing pharmacy-level substitution, where state law permits. In the USA, two ADL biosimilars have received interchangeability designation; others are seeking interchangeability designation from the Food and Drug Administration (n = 2), are being evaluated in clinical studies to support interchangeability (n = 2), or do not have/are not seeking interchangeability designation (n = 3). Product-related attributes influence patient experience of ISP caused by subcutaneous ADL injection. Reference ADL and ADL biosimilar products differ in their attributes, so discussion with patients about treatment options is essential to optimize adherence and outcomes.