Is the local tolerance of injectable biosimilars too underestimated?

Submitted: 23 September 2020; Revised: 2 October 2020; Accepted: 6 October 2020; Published online first: 12 October 2020

The previous issue of GaBI Journal published a manuscript entitled ‘Systematic analysis of injection-site pain and reactions caused by subcutaneous administration of the adalimumab biosimilar FKB327 versus the adalimumab reference product via different delivery methods’ by Alten et al. [1]. The topic of this article is of importance as there are very few biosimilar evaluations devoted to minor side effects. As with new molecules, the published clinical trials of biosimilars mainly focus on major side effects, such as haematological, cardiac, or neurological disturbances. As a result, effects without major clinical consequence, from the medical practitioner’s point of view, such as pain during injections, low intensity itching, or even slight fatigue, are poorly reported and thus underestimated. This is even more evident in the clinical trials requested for the registration of a biosimilar. However, these effects often cause discomfort for patients and can play a fundamental but poorly evidenced role in the acceptability of the biosimilar and in the prescriber’s willingness to use it. If a biosimilar, especially those authorized by the European Medicines Agency (EMA) or the US Food and Drug Administration (FDA), is by ­definition highly comparable to its originator, the two drugs should have identical tolerability. This is obviously true for major side effects but is open for debate when it comes to local tolerance during injection. In fact, the composition of the excipients may vary between formulations, and the quality of packaging such as syringes including the needles, may induce different local reactions.

The problem with well-evaluated biosimilars is not that of their quality but that of their acceptability by prescribers and their patients. As such, it is crucial to have precise and well-designed clinical data allowing objective judgement of the local tolerance of a biosimilar in relation to its originator or other competing biosimilars. However, this is not the only way to increase the acceptability of biosimilars. Instead, detailed and objective information for patients and prescribers remains crucial and has proven effective.

For biologicals mainly prescribed and used by the patient at home by self-injection, such as adalimumab, comfort and local tolerance are key elements of acceptability. Though these can be considered less important for biologicals administered in hospital environment and for short time periods, such as monoclonal ­antibodies used in oncology. As such, when it comes to making the choice between the originator and its biosimilars or between biosimilars in hospitals, comfort and local tolerance play a less significant part due to the important role played by product price when it comes to hospital tenders. Moreover, the hospital environment rarely encourages listening to the complaints of patients who are often dependent or sometimes infantilized.

In light of this, this article on the local tolerance of a new biosimilar of adalimumab as compared to its originator (Humira^TM) [1] is particularly welcome as this kind of comparison is rarely published. It is also interesting as it addresses several ways of administration, giving a global picture of the local tolerance of this biosimilar in comparison to its originator. In addition, the article compares the tolerance of the biosimilar formulation without citrate, to the originator containing citrate. However, a new formulation of the originator is now on the market without citrate demonstrating that, under the same brand name, different formulations can exist. This has the potential to cause confusion amongst prescribers and pharmacists. As such, it may be considered necessary to carry out a study that compares the formulations without citrate.

This article is of particular importance as it has published data that has allowed the practical use of a biosimilar to be evaluated. Thus, it allows an informed choice between the originator and its different biosimilars and/or between biosimilars, to be made. This information gives appreciable additional value to the landscape of competing biosimilars of the same originator.

Competing interests: None.

Provenance and peer review: Commissioned; internally peer reviewed.

References
1. Alten R, Kellner H, Boyce M, Yonemura T, Ito T, Genovese MC. Systematic analysis of injection-site pain and reactions caused by subcutaneous administration of the adalimumab biosimilar FKB327 versus the adalimumab reference product via different delivery methods. Generics and Biosimilars Initiative Journal (GaBI Journal). 2020;9(3):108-15. doi:10.5639/gabij.2020.0903.019

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