Studies Disagree on the Role of Education, Nocebo Effect in Biosimilar Switching

The nocebo effect, whereby a patient experiences a worsening of symptoms or poor outcomes because of negative beliefs about a given therapy, has been the subject of increasing discussion among biosimilar stakeholders who fear that the effect may be to blame for discontinuation of biosimilars after switching from the reference.

During this week’s European League Against Rheumatism (EULAR) European Congress of Rheumatology 2019, 2 research teams will present their contrasting findings on education and the nocebo effect.

One study on the nocebo effect assessed the efficacy of a multidisciplinary team’s intervention to reduce nocebo among patients with inflammatory arthritis who were switched from reference infliximab to SB2 (Renflexis).¹

The intervention was part of a 2018 patient education program that comprised 4 steps: qualitative interviews with 5 patients treated with other biologics to assess knowledge and attitudes, a meeting with a multidisciplinary team of providers and a peer patient to design the intervention, agreement on the intervention and language to be used by providers, and implementation.

A total of 45 patients were included in the study. The retention rate after the switch was 91.2%. One patient reported fatigue and pain, which were classified by the investigators as nonspecific subjective adverse events (NSAEs). During the same period, 18 patients who were being treated with biosimilar CT-P13 (Inflectra, Remsima) also switched to biosimilar SB2, with a retention rate of 66.7% and 1 reported NSAE.

According to the authors, these results demonstrate that multidisciplinary patient education is effective in reducing the nocebo effect when switching to a biosimilar.

Much has been made of the issue of the nocebo effect, however, not all experts agree that it plays a role in discontinuation. Another study being presented at EULAR seems to suggest that education was not an important factor in a different yet also successful switch.

The study sought to evaluate the safety and efficacy of a systematic nonmedical switch from the reference etanercept to SB4 (Eticovo, Brenzys, Benpali) in adults with rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis in a real-world setting.²

The investigators analyzed data on all 84 adult patients who were switched to SB4 for economic reasons. Disease activity and function were assessed regularly, and changes were recorded at week 12 and week 24.

Patients were informed about the switch at the discretion of the treating physician. In total, 24 patients (28.5%) had been informed about the switch.

At week 12, disease activity and function scores were largely unchanged from pre-switch values. Whether patients had been informed about the switch did not correspond with different outcomes or adverse events (AEs). Retention on the biosimilar was 96.4% at week 12, and 87.6% at week 24. In total, 7 patients were lost to follow-up, and 6 discontinued due to inefficacy or AE.

Overall, 18 AEs were reported in 10 patients (12%). Three patients who had 5 AEs during the first 12 weeks were switched back to the reference.

The researchers concluded that a switch to the biosimilar was not related to changes in disease activity or function, and that patient education did not impact the success of the switch.

References

1. Petit J, Antignac M, Poilverd RM, et al. How to reduce the nocebo effect when switching from originator infliximab to a biosimilar: positive results of a multidisciplinary team intervention. Presented at: The European League Against Rheumatism European Congress of Rheumatology 2019, June 12-15, 2019; Madrid, Spain. Abstract SAT0690.

2. Kiltz U, Tsiami S, Baraliakos X, Braun J. Non-medical switching from originator to biosimilar etanercept—no evidence for a relevant nocebo effect—a retrospective analysis of real-life data. Presented at: The European League Against Rheumatism European Congress of Rheumatology 2019, June 12-15, 2019; Madrid, Spain. Abstract FRI0101.