Clinical Evidence Shows No Safety Gaps Between Biosimilar, Reference Adalimumab

A plain language summary of safety results from the VOLTAIRE clinical trials described the results of a recent pooled analysis of safety data in patients with rheumatoid arthritis (RA), Crohn disease (CD), and chronic plaque psoriasis, which found no differences in safety outcomes between adalimumab-adbm (Cyltezo) and the reference product (Humira).

The purpose of the summary, according to authors from Boehringer Ingelheim, is to help patients understand the findings and help health care professionals make treatment decisions. The summary included concise explanations of the results and their meaning, the conditions included, study designs, and definitions of biologics, biosimilars, interchangeability, and adverse events. It also provided links to external resources, including the original pooled safety publication and plain language summaries of the individual VOLTAIRE trials.

Biosimilars referencing adalimumab, a monoclonal antibody targeting tumor necrosis factor-α, first entered the US market in 2023, and Cyltezo was the first adalimumab biosimilar to gain the interchangeable designation in the US.

The 5 VOLTAIRE clinical trials compared effectiveness and safety of continually receiving the adalimumab originator to switching one or more times between the originator and Cyltezo in patients with RA (VOLTAIRE-RA, VOLTAIRE-RAext), Crohn disease (VOLTAIRE-CD), and chronic plaque psoriasis (VOLTAIRE-X, VOLTAIRE-PsO). Pooled safety results of all five trials were published in November 2024. The authors of the summary explained that the data was pooled “to provide a better understanding of the overall safety” of adalimumab-adbm.

Across all VOLTAIRE clinical trials, there were 1368 participants, 645 in VOLTAIRE-RA, 147 in VOLTAIRE-CD, 317 in VOLTAIRE-PsO, and 259 in VOLTAIRE-X. The pooled analysis evaluated total and serious adverse events (AEs), discontinuation of treatment due to AEs, deaths, and AEs of special interest, which included serious infections, cancers, and major adverse cardiac-related events. The researchers also investigated whether there were any differences in safety based on sex or age group.

In the pooled analysis, rates of AEs, serious AEs, and discontinuations were similar in patients with RA and chronic plaque psoriasis, regardless of whether they were treated with Cyltezo or the originator. Patients with CD had “slightly higher” rates of AEs, serious AEs, and discontinuations than the other two conditions in both biosimilar and reference product groups. There were no significant differences in deaths between conditions or between biosimilar and reference product groups. There were also no significant differences in safety outcomes between treatments in patients who were 65 or older, or those who were under 65.

Cancers and major adverse cardiac-related events were only reported in patients with RA and were not significantly different between treatment groups. Serious infections were reported in patients with RA and chronic plaque psoriasis, and there were no significant differences between groups. There were no AEs of special interest observed in patients with CD.

Limitations of the VOLTAIRE trials discussed by the authors included that the participants were predominantly white, thus the results may not be representative of all patients, and that the findings may not be applicable to patients with autoimmune conditions other than those included in the trials. When explaining the meaning of the results, the authors said since there were no differences in safety outcomes between biosimilar and reference product groups across the VOLTAIRE trials, patients with RA, CD, and chronic plaque psoriasis who take Cyltezo can expect similar side effects to those of the reference product.

Reference

Cohen S, Bender S, Shaberman A, Vinisko R, McCabe D. A plain language summary of the pooled safety results of adalimumab-adbm from the VOLTAIRE clinical trials in people with rheumatoid arthritis, Crohn's disease, and chronic plaque psoriasis. Expert Opin Biol Ther. 2025;25(4):323-329. doi:10.1080/14712598.2025.2476033