Study on Nonmedical Switching for Adalimumab Biosimilars Warns About Nocebo Effect

A real-world analysis from Italy assessing nonmedical switches from Humira (reference adalimumab) to a biosimilar or an adalimumab biosimilar to another biosimilar resulted in some worsening patient-reported outcomes (PROs), which were mostly attributed to the nocebo effect.

The assessment is one of the first studies comparing the real-world effectiveness of nonmedical switching from Humira to an adalimumab biosimilar and between adalimumab biosimilars. The researchers said that their results emphasize the importance for better communication between physicians and patients to ensure that patients’ negative perceptions of biosimilars do not result in worsening PROs.

Humira and adalimumab biosimilars are used to treat several conditions including rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (axSpA), Crohn disease, and ulcerative colitis.

The study analyzed data from patients with inflammatory conditions who switched from Humira or ABP501 (Amgevita), an adalimumab biosimilar, to SB5 (Imraldi), another adalimumab biosimilar, who were treated at the Arthritis Center outpatient clinic at Sapienza University of Rome. Patients gave written consent for the researchers to use their data and the data was followed up to 4 months post switch.

Overall, 110 patients originally taking Humira and 40 patients treated with ABP501 were included, 48.6% of whom were women; the median age was 56 years. By disease state, 33 patients from the Humira group and 12 from the ABP501 group had RA, 40 from the Humira group and 25 from the ABP201 group had PsA, and 37 in the Humira group and 3 from the ABP201 group had axSpA.

In the originator-to-SB5 group, at 4 months post switch, the researchers noted a significant reduction of patients in remission or with low disease activity (P = .009), with a risk reduction (RR) of moderate-high disease activity significantly higher after the switch (RR, 2.6; 95% CI, 1.2-5.7; P = .01). No differences in Disease Activity Score 28 (DAS-28-CRP), disease activity index for psoriatic arthritis (DAPSA), Ankylosing Spondylitis Disease Activity Scores, or Bath Ankylosing Spondylitis Disease Activity Index scores were observed. Twelve patients (10.9%) switched back to the originator, mostly due to lack of efficacy in join involvement or recurrent uveitis.

In the biosimilar-to-biosimilar group, at 4 months after switching, no differences in DAS-28-CRP and DAPSA or changes in the percentage of patients in remission or with low disease activity were found. Also, no differences in PROs were observed. Six patients discontinued SB5 before the end of the follow-up period for lack of efficacy (n = 3) or adverse events (n = 3).

Although the biosimilar-to-biosimilar group had less patients than the originator-to-biosimilar group, the differences in PROs suggests that the nocebo effect may have had an impact. The nocebo effect occurs when a patient’s negative perception about a medication results in reduced effectiveness or adverse events (AEs).

However, the researchers noted that a combination of factors, including the nocebo effect, differences in molecular structures, excipients, and injection devices, could have resulted in reduced PROs.

“In our study, based on the different results obtained after the switch in the 2 groups, we cannot rule out that patients treated with ABP501 biosimilar may be less affected by the nocebo effect than patients initially treated with the bio-originator. Indeed, it is known that switching from an originator to a biosimilar can result in nocebo responses, including a subjective increase in disease activity and pain-related AEs,” they wrote.

The main limitations were population size, the disparities between the 2 groups, and the short follow-up period.

“Nevertheless, our results replicate those reported in the literature, providing a reassuring profile of effectiveness when switching from [adalimumab] originator to one of its biosimilars and between 2 different biosimilars. However, the worse outcome in PROs in patients initially treated with the bio-originator addresses the attention to a possible nocebo response, which should encourage comprehensive communication with patients.”

Reference

Scrivo R, Castellani C, Mancuso S, et al. Effectiveness of non-medical switch from adalimumab bio-originator to SB5 biosimilar and from ABP501 adalimumab biosimilar to SB5 biosimilar in patients with chronic inflammatory arthropathies: a monocentric observational study. Clin Exp Rheumatol. 2023;41(3):613-619. doi: 10.55563/clinexprheumatol/bf00j9