Evaluating Adalimumab Biosimilar Switch Impact on Disease Flares, Tolerability

A retrospective cohort study in the Netherlands evaluated the real-world effectiveness of the biosimilar adalimumab Hyrimoz (GP2017) after switching from the reference product (Humira) in patients with a variety of immune-mediated inflammatory diseases.

The incidence of flares, which was the primary endpoint, was not significantly different during treatment with the biosimilar compared to the originator. However, one-quarter of patients experienced adverse events after switching to Hyrimoz, primarily injection site reactions that prompted some patients to switch back to the reference product. The authors attributed this to the larger injection volume and presence of citrate in the biosimilar formulation.

GP2017 (Hyrimoz) is 1 of 10 biosimilars referencing adalimumab, a monoclonal antibody that binds tumor necrosis factor (TNF)-alpha and inhibits its pro-inflammatory effects. The center switched patients from the adalimumab originator to Hyrimoz in 2022, and data were collected from patient records for the period 1 year prior to and 1 year following the switch in 185 patients. Indications for adalimumab treatment were systemic disease with uveitis in 32% of patients, isolated uveitis (22%), Behçet disease (without active uveitis; 20%), and (neuro)sarcoidosis (12%).

The number of flares was not significantly different during treatment with the reference adalimumab compared to Hyrimoz. During 1 year of treatment with the reference product, 29 flares in 28 patients were reported, and in the one year after switching, 24 flares in 23 patients were reported.

The investigators compared patient characteristics between those who experienced a flare during Hyrimoz treatment and those who did not. No significant differences in sex, age, or indication for adalimumab treatment were observed. However, those who experienced a flare during treatment with the biosimilar experienced more adverse effects than those who did not.

Of the 185 patients, 46 (25%) experienced adverse effects. The most frequently reported adverse effect was pain during injection, reported by 25 patients (13.5%). About one-third of patients (60; 32%) discontinued treatment with Hyrimoz, including 17 (9%) because of flares, 27 (15%) because of adverse effects, and 15 (8%) because of subjective disease symptoms.

Of the adverse effects leading to discontinuation, pain during injection was the most frequent.

Both the reference product and biosimilar were available as pre-filled syringes and autoinjectors, which were prescribed based on the patients’ preference. Notably, the formulation of the reference product used at the center did not contain citrate, however, the biosimilar did contain citrate and had a larger injection volume, attributes previously linked to injection-site pain. Since injection-site pain led some patients to switch back to the reference product and was the most reported adverse effect, the authors said pain with Hyrimoz injection is “a major concern” when switching from the reference product to this biosimilar.

Of the 23 patients who experienced a flare during biosimilar treatment, 17 (74%) switched back to the reference product, and the authors noted that in most cases this switch led to inactive disease. Although the reasons are unclear, they said low drug levels due to non-adherence or formation of antidrug antibodies could be responsible. However, drug and antibody levels were measured only in a “minority” of patients in this study, preventing the authors from drawing conclusions. They added that future research should include serum drug and antibody measurements.

Reference

van Poecke WHA, Hooi NEF, Mossel TK, Hermans MAW, van Daele PLA, Bunnik EM, Brkic Z, Sels LK, Thiadens AAHJ, van Hagen PM, van Laar JAM, Rombach SM. Impact of switching from the originator adalimumab to a biosimilar: a retrospective cohort study. BMC Immunol. 2025;26(1):44. doi:10.1186/s12865-025-00693-9