All biologic medications, including reference products (also known as the originator or innovator products), come from living systems (e.g. bacteria and yeast). Thus, it is nearly impossible to consistently create an identical copy of a biologic. Even with the same reference product produced by the same manufacturing plant using the same cell line, dissimilarities can exist from batch to batch. To be approved by the FDA, biosimilars must have (1) identical therapeutic amino acid sequences relative to the reference product and (2) demonstrate biosimilarity through pharmacodynamic, pharmacokinetic, and immunogenicity studies.

Most biosimilars obtain FDA approval in psoriasis and psoriatic arthritis via extrapolation. Extrapolation is an established scientific and regulatory principle where biosimilarity to the reference product has been shown by a comprehensive comparability program, including safety, efficacy, and immunogenicity for another indication (e.g. rheumatoid arthritis). Thus, most biosimilars for psoriasis and psoriatic arthritis are approved without the need to repeat clinical trials. Such designation is not automatic and is based on assessment of scientific justification. Of note, some biosimilars may differ from the reference product in certain aspects, including delivery device, product concentration, and citrate content. However, for all practical purposes, we deem biosimilars approved by the FDA to be similar in efficacy and safety to the reference product in treating psoriasis and psoriatic arthritis.

In the U.S., some biosimilars have an additional regulatory designation termed “interchangeability,” which means that the biosimilar can be substituted for its reference product at the pharmacy without additional approval from the prescribing physician. The interchangeable designation may be granted for a biosimilar when additional “switching” clinical studies demonstrate no additional risk or reduced efficacy, if a patient switches back and forth between a reference product and a biosimilar, as compared to continuing on the reference product. Although interchangeability is granted at the federal level by the FDA, state laws govern (1) local dispensing and substitution of drugs at the pharmacy level and (2) whether to notify patients or providers about the substitution. Potential cost-savings may occur when a pharmacy substitutes a reference product with an interchangeable biosimilar. We recognize and concur with the substitution of reference products for interchangeable biosimilars at the pharmacy.

If a patient loses efficacy or tolerability to a reference product or its biosimilar product, we urge clinicians to consider a different medication. Due to the biosimilarity between the reference product and all of its biosimilars, the etiology for a patient’s loss of efficacy or tolerability to a reference product or to one of its biosimilars is likely to be extrapolated to another biosimilar of the same reference product.