Switching Patterns Highlight Nocebo Effect in European Patients Using Amgevita

About half of European patients with rheumatic conditions who switched from reference adalimumab (Humira) to the biosimilar ABP501 (Amgevita in Europe, Amjevita in the US) stayed on the biosimilar after 12 months, but many switched back to Humira, suggesting a possible nocebo effect.¹

Immune-mediated inflammatory diseases—like rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS)—cause chronic joint pain and structural damage if untreated. Tumor necrosis factor inhibitor (TNFi) biologics, such as adalimumab, have improved disease management, especially for those unresponsive to conventional treatments.

Recently approved TNFi biosimilars, including ABP 501, offer additional treatment options. ABP 501 was the first adalimumab biosimilar approved in Europe (2017) and the US (2016), based on comprehensive evidence of its similarity to the reference product. Although ABP 501 was available upon approval for European patients, patent disputes forced Amgen, the biosimilar’s developer, to wait until January 2023 to launch in the US.² Clinical trials confirmed its efficacy and safety, but real-world data, especially for PsA and AS, are limited.

A retrospective cohort analysis published in Rheumatology and Therapy was conducted to evaluate the use of ABP 501 in treating RA, PsA, and AS and utilized the IQVIA German and French pharmacy claims Longitudinal Prescription Data database through April 30, 2021. For inclusion, patients had to be 18 years or older and had at least 1 prescription of ABP 501 between October 2018 and March 2020. Patients also had to have at least 365 days of continuous observation of overall pharmacy records in the database before initiating therapy with the biosimilar.

Persistence was evaluated using Kaplan-Meier analysis with a 120-day prescription gap (90 days for sensitivity analysis). Adherence was measured by the medical possession ratio, with 80% or higher considered adherent. Switching patterns to other therapies post ABP 501 were tracked. Patient characteristics, prior treatment history, and concomitant treatments were analyzed, stratified by previous adalimumab use.

Overall, 6739 German patients (RA, n = 2725; PsA, n = 1739; AS, n = 2275) and 2016 French patients (RA, n = 827; PsA, n = 243; AS, n = 946) were evaluated as part of the study. Most patients were treated by rheumatologists. In both Germany and France, patients with RA and PsA, especially those naïve to adalimumab, commonly used conventional synthetic disease-modifying antirheumatic drugs, glucocorticoids, and sometimes biologics or Janus kinase (JAK) inhibitors before starting ABP 501, and some continued these treatments during ABP 501 therapy.

Treatment persistence with ABP 501 was similar across indications and countries, with median persistence ranging from 9.4 to 12.1 months in Germany and 7.1 to 11.7 months in France for RA, PsA, and AS. At 12 months, the persistence rate was 44% to 51% in Germany and 32% to 50% in France. German patients experienced with adalimumab had longer persistence compared with adalimumab-naïve patients, while in France, persistence was more comparable between these groups.

Over 40% of German patients were adherent to ABP 501 in the first 12 months, whereas adherence in France ranged from 31.3% to 37.7%.

Among patients who discontinued ABP 501 after 12 months, 25% to 32% did not switch to another therapy, 12% to 31% resumed ABP 501 after a gap, and 43% to 63% switched to another targeted therapy. Adalimumab-naïve patients often switched to nonadalimumab TNFi, non-TNFi biologics, or JAK inhibitors (for RA), while adalimumab-experienced patients frequently switched back to the reference product.

Although the researchers couldn’t pinpoint patients’ exact reasons for switching back to the reference product, they said the nocebo effect may have played a part. The nocebo effect occurs when patients’ negative emotions about a product result in adverse events that are not caused by the medication.

“Future studies are warranted to elucidate underlying reason(s) for biosimilar discontinuation/switching and evaluate potential nocebo effect, if any, in patients with rheumatologic diseases. Providing evidence-based communication to patients and their treating physicians should help to improve treatment persistence and adherence and result in more positive treatment outcomes for patients,” the authors wrote.

The study had several limitations, including potential misclassification of diseases due to imputed diagnoses, although the model was 95% accurate. The IQVIA database excluded hospital-dispensed medications, possibly missing some treatment histories. Baseline clinical characteristics were not recorded, and the study period included the COVID-19 pandemic, which may have influenced treatment patterns.

References

1. Jin R, Kruppert S, Scholz F. Treatment persistence and switching patterns of adalimumab biosimilar ABP 501 in European patients with rheumatologic diseases. Rheumatol Ther. 2024;11(3):523-537. doi:10.1007/s40744-024-00647-4

2. Jeremias S. US welcomes first adalimumab biosimilar, Amjevita. The Center for Biosimilars®. January 31, 2023. Accessed July 22, 2024. https://www.centerforbiosimilars.com/view/us-welcomes-first-adalimumab-biosimilar-amjevita