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Switch to Adalimumab Biosimilar Safe, Effective for Uveitis, but the Nocebo Effect Persists


Switching patients with non-infectious uveitis from originator adalimumab to biosimilar adalimumab-atto was safe and effective, but some patients experienced the nocebo effect, where negative adverse events are caused by patients’ poor perception of the drug rather than the medication itself.

Doctors review research. | Image Credit: SpaceOak - stock.adobe.com

Research finds switching from the originator to adalimumab biosimilar is safe and effective. | Image Credit: SpaceOak - stock.adobe.com

Patients with non-infectious uveitis exhibited similar clinical outcomes after switching from originator adalimumab (Humira) to biosimilar adalimumab-atto (Amgevita), showing that the 2 products exhibit comparable safety and efficacy as the safety of switching between adalimumab products, according to a study published in Ocular Immunology and Inflammation.1

Once a patent ends for a medication, drug developers take advantage of nonmedical switching implementations, which is when patients swap medications for another for reasons not related to clinical outcomes—usually as a means to save money. However, some patients are not as eager to switch to biosimilars because they are fearful of potential loss of efficacy, changes in immunogenicity, and differences in safety compared with the originators.

There have been previous reports of “failed switches”, when patients request to switch back to the originator after unsuccessfully swapping to the biosimilar. However, this is usually due to adverse events that are not treatment emergent and are typically rooted in the patients’ personal preferences.

A retrospective research study was conducted among pediatric and adult patients with uveitis from 3 tertiary centers in the United Kingdom. The study was based on a mandatory change across all 3 institutions from reference adalimumab to adalimumab-atto.

There were 102 participants included in the analysis that switched from adalimumab to adalimumab-atto and had stopped adalimumab based on disease remission but began adalimumab-atto after a flare of disease within 6 months of stopping treatment.

Methotrexate was used to treat all pediatric patients but 25% stopped administration based on adverse effects, most commonly gastrointestinal-related nausea. Out of all the patients that stopped methotrexate, 88% switched to another disease-modifying antirheumatic drug (mycophenolate mofetil).

Some pediatric patients had periods of time where they went off adalimumab but experienced flares of eye disease when restarting treatment.

After switching to adalimumab-atto, there was 1 case of worsening visual acuity and 2 events of improved visual acuity. Researchers did not find significant differences in the number flare cases or the dosage of glucorticosteroids used between the 2 groups. Less patients in the post-switch group had raised intraocular pressure compared with the pre-switch group. Flares were mild for both groups.

Around 20 patients reported experiencing adverse events after switching. The most common adverse event was an increased injection site pain (65.0%), with the majority of reports stemming from the pediatric patients (92.3%). Other adverse events reported included localized skin reactions, decreased vision, and technical issues with the injector device.

Less than half of the study population switched back to adalimumab (24.0%),most of whom were pediatric patients (n = 15/24). Only 1 patient that switched back had an allergic reaction to the biosimilar. Every patient that switched back to adalimumab did so based on individual request due to discomfort from the new injection device and never in relation to a flare in uveitis disease activity.

The authors noted the increased injection site pain in the biosimilar group may have been due to the biosimilar having a slightly larger gauge needle than the originator.

Biosimilar introduction was expected to be followed by market competition that resulted in decreased costs of development and affordability for patients. For adalimumab-atto to be considered more cost effective, the biosimilar would need to be 84% than the originator. The decrease in costs for bio-originator medications has the potential to offer low- and middle-income countries accessibility to biologics.

Research presented at the American Academy of Dermatology annual meeting confirmed safety and efficacy when switching patients with different types of psoriasis from reference ustekinumab (Stelara) to SB17, a ustekinumab biosimilar candidate, and reference adalimumab (Humira) to a biosimilar version (Imraldi).2 Similarly to patients with non-infectious uveitis, patients with psoriasis that had negative opinions towards biosimilars experienced nocebo effect-related adverse events after switching.

In a survey of physicians and patients, higher reports of disease severity, poor treatment adherence, and decreased quality of life were detected among groups that switched from an originator to a biosimilar.3 Rheumatologists should be advised of the potential negative assumptions towards nonmedical switching and continuously exercise communication efforts to prevent negative outcomes caused by the nocebo effect.

Other factors that could contribute to the nocebo effect include patient reluctance to switching from medications they are satisfied with, provider’s lack of confidence in biosimilars, and the perception that biosimilars are low quality versions of originators.3

Study limitations included limited in-person appointments during the COVID-19 pandemic, the pediatric patient population being from small area, and retrospective design.1

The researchers concluded that more research is needed to optimize clinical considerations for patients switching from originators to biosimilars.


1. Murray GM, Griffith N, Sinnappurajar P, et al. Clinical efficacy of biosimilar switch of adalimumab for management of uveitis. Ocul Immunol Inflamm. 2024;32(4):442-446. doi:10.1080/09273948.2023.2172591

2. Jeremias S. AAD posters examine clinical effects of switching to ustekinumab, adalimumab biosimilars. The Center for Biosimilars®. March 20, 2024. Accessed June 12, 2024. https://www.centerforbiosimilars.com/view/aad-posters-examine-clinical-effects-of-switching-to-ustekinumab-adalimumab-biosimilars

3. Ferreri D. Nocebo effect leads to switched patients reporting greater disease severity, poorer quality of life vs nonswitched patients. The Center for Biosimilars®. June 13, 2023. Accessed June 12, 2024. https://www.centerforbiosimilars.com/view/nocebo-effect-leads-to-switched-patients-reporting-greater-disease-severity-poorer-quality-of-life-vs-non-switched-patients

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