Study: Does Adalimumab Lose Effectiveness After Switching to a Biosimilar?

The authors of an Italian retrospective real-world study of 326 adult patients with hidradenitis suppurativa (HS) treated with adalimumab concluded that switching patients between adalimumab products risked a greater likelihood of loss of effectiveness, in contrast to much of the existing evidence on switching from the adalimumab reference product (Humira) to a biosimilar.

“This result seems to suggest that, if a patient starts adalimumab, whether originator or biosimilar, it should not be switched,” they wrote.

Adalimumab, a tumor necrosis factor (TNF) alpha inhibitor, is the only biologic therapy approved in the European Union for treatment of moderate-to-severe hidradenitis suppurativa (HS), an inflammatory skin disease, according to the authors of the study, conducted at 14 sites throughout Italy.

The authors said some concerns have been raised about the effectiveness of adalimumab biosimilars in patients previously treated with the reference product. With anti-TNF biologics, they said “it is known that neutralizing antibodies can be created during treatment,” which could then limit the effectiveness of another therapy based on the same molecule. However, a 2021 systematic review of intervention studies on switching from the adalimumab originator to biosimilars found no differences in efficacy, safety, and immunogenicity between switch and no-switch groups.

Just over half (n = 171; 52.5%) of patients in the retrospective study initiated therapy with the reference product and did not switch; 61 (18.7%) began with a biosimilar and did not switch; 66 (20.2%) initiated therapy with the reference product and switched to a biosimilar; and 28 (8.6%) switched twice, from the reference product to the biosimilar, then back. No patients initiated therapy with the biosimilar and switched to the reference product. Effectiveness of therapy was indicated by Hurley scores.

Of the 265 patients who began adalimumab therapy with the reference product, 171 (64.5%) were still taking the reference product at the last follow-up, and 94 (35.6%) had switched to the biosimilar. Among those who switched, 4 (4.3%) patients’ Hurley scores worsened and 31 (33.7%) improved. Among those who remained on the reference product, none worsened and 68 (39.8%) improved at the last available follow-up.

In a time-to-ineffectiveness analysis, the authors observed that treatment ineffectiveness occurred more quickly in those who initiated treatment with a biosimilar compared to those who initiated treatment with the originator (HR=3.5, 95% confidence interval 2.2-5.6), after adjustment for baseline clinical variables.

Among the 94 patients who switched from the reference product to a biosimilar, the authors found a greater likelihood of loss of effectiveness during biosimilar treatment, which they hypothesized could be explained by immunogenicity. The authors also noted the reference product was received first in all cases. Since no patients initiated treatment with a biosimilar and switched to the originator, the authors could not compare patients who switched from reference product to biosimilar to those who switched in the opposite direction.

They also evaluated effectiveness in the 28 patients who switched back to the originator because of loss of effectiveness after switching to a biosimilar (30% of the patients who switched to a biosimilar). After switching to a biosimilar, most patients (n = 22; 79%) had a stable Hurley score, and 6 (21%) worsened. After switching back, 5 (18%) patients improved, and 23 (82%) had a stable Hurley score. According to the investigators, these findings suggest the possibility that there is a subset of patients who were responders to the reference product but did not respond to a biosimilar.

The use of the Hurley score as an outcome measure was a limitation of the study, the authors said, because it “is not sensitive to changes and cannot provide a global severity measure.” They added the fact that no patients initiated treatment with a biosimilar switched to the reference product was another limitation. All switches to a biosimilar were for economic reasons, they said.

Additionally, the Hurley scores were assessed at the time of switching, which may have caused some bias favoring the former treatment.

“Indeed, the switch was not due to a loss of efficacy, but to economic reasons. Once the patients switched to biosimilar, starting from a lower Hurley score, an improvement was observable…. Further studies on this topic are needed, in order to deepen our understanding of these issues.”

Importantly, Canada along with many European countries have real-world experience with switching patients from a reference adalimumab to a biosimilar without compromised clinical efficacy. A systematic review from 2018 has also found that switching between reference products and biosimilars is safe, and there is a growing body of evidence showing that switching from a biosimilar to another biosimilar does not impact clinical safety or effectiveness.

Reference

Burlando M, Fabbrocini G, Marasca C, et al. Adalimumab originator vs. biosimilar in hidradenitis suppurativa: a multicentric retrospective study. Biomedicines. 2022;10(10):2522. doi:10.3390/biomedicines10102522