Adalimumab Biosimilar May Reduce Antibody Response After COVID-19 Vaccine

David Vetchý, PhD

Credit: Masaryk University

A new retrospective study assessed the SARS-CoV-2 antibody response after immunization with a mRNA vaccine among patients with rheumatoid autoimmune diseases treated with originator adalimumab, an adalimumab biosimilar, or without the biological agent.¹

Results from the study confirmed that individuals with autoimmune rheumatic diseases, including rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA), treated with adalimumab developed cellular immune responses on day 21 after the second vaccination dose.

However, longer-term data after the second dose revealed the SARS-CoV-2 antibody levels did not change significantly in those receiving the originator adalimumab, while those receiving the biosimilar experienced a significant decrease in antibody levels. Healthy individuals showed a significantly higher level of antibodies in that same period.

“Our observation showed no statistically significant difference between patients treated with the original adalimumab and biosimilar adalimumab at day 21,” wrote the investigative team led by David Vetchý, PhD, the dean of faculty of pharmacy at Masaryk University. “The lower level of antibodies by subjects treated with biologics was expected based on the previous studies.”

Biosimilars have the potential for reduced costs of biological treatment, with introduction into the market after the expiration of the patent protection of the originator.² Biosimilars are highly analytically similar to the originator product, with no clinically significant differences in purity, potency, pharmacokinetics (PK), pharmacodynamics, clinical efficacy, safety, and immunogenicity.

Vaccination against COVID-19 is recommended for patients with autoimmune diseases, as this population is at increased risk of developing severe disease.³ However, evidence has suggested protective immunity after COVID-19 vaccination is at risk of being affected by treatment with immunosuppressive medication in those with autoimmune diseases.

Studies investigating the impact of biological disease-modifying antirheumatic drugs (DMARDs) on SARS-CoV-2 antibody responses are accumulating, but data are scarce on the effect of both originator and biosimilar adalimumab on the immune response to COVID-19 vaccines.¹

The current retrospective study’s primary endpoint was the differences in SARS-CoV-2 antibody levels between patients treated with the originator product and biosimilar adalimumab (MSB11022), as well as the differences in antibody levels between those treated with and without biological treatment.

Investigators obtained the gender, autoimmune disease type, age, and treatment history of patients with autoimmune rheumatic diseases in an outpatient clinic in the Czech Republic. A total of 63 patients aged ≥18 years had all received the COVID-19 mRNA vaccine, with a 21-day gap between the two vaccinations. Each patient underwent treatment with adalimumab and/or methotrexate 10–25mg per week for ≥12 weeks before the first dose of the SARS-CoV-2 vaccine.

Upon analysis, the comparison of SARS-CoV-2 antibody levels revealed no observable differences between patients treated with original and biosimilar adalimumab at day 21, with median levels of 10.2 and 11.1 U/mL, respectively. At day 63, the analysis showed a significant increase in antibodies, regardless of the treatment type.

Investigators observed higher levels of SARS-CoV-2 antibodies in those without biological treatment than the biological treatment group, regardless of the originator or biosimilar drug type. A statistically significant difference in antibody levels between those without biological treatment (median, 504.3 U/mL) and those with originator (median, 47.2 U/mL) or biosimilar (median, 28.2 U/mL) adalimumab treatment was confirmed by the investigative team on day 182.

From day 63 to day 182 after the second vaccination dose, Vetchy and colleagues found the SARS-CoV-2 antibody levels did not drastically change in the originator and without biological treatment cohorts. Meanwhile, the biosimilar cohort experienced a significant decrease in antibody levels.

“According to our observation, the effect of the treatment type on the increase/decrease of antibodies over time is dominant, while the impact of other variables (gender, methotrexate treatment, autoimmune disease type, and age) was confirmed as insignificant or minor,” investigators wrote.

References

1. _{Dokoupilová E, Vetchý D, Pavloková S, Hanuštiaková M. Effect of treatment with original or biosimilar adalimumab on SARS-CoV2 vaccination antibody titers. Int J Pharm X. 2024;7:100229. Published 2024 Jan 6. doi:10.1016/j.ijpx.2024.100229}
2. _{Center for Drug Evaluation and Research. Scientific considerations in demonstrating biosimilarity. U.S. Food and Drug Administration. Accessed February 6, 2024. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/scientific-considerations-demonstrating-biosimilarity-reference-product.}
3. _{Furer V, Rondaan C, Agmon-Levin N, et al. Point of view on the vaccination against COVID-19 in patients with autoimmune inflammatory rheumatic diseases. RMD Open. 2021;7(1):e001594. doi:10.1136/rmdopen-2021-001594}