Editorial Argues That Nocebo Effect Could Harm Patients Who Switch to Biosimilars

In a trial published¹ in Alimentary Pharmacology & Therapeutics in December 2017, researchers conducted a switching study in patients who had been receiving reference infliximab (Remicade) to biosimilar infliximab (Inflectra). The trial found that there were no differences in drug levels or disease activity when adult patients with inflammatory bowel disease (IBD) were switched as part of routine care.

Due to these positive results, the study’s authors concluded that switching to the biosimilar and performing therapeutic drug monitoring as part of routine care optimizes infliximab therapy efficiently and makes it more cost effective.

In a recently published editorial linked to the study², authors Adrian Van Bodegraven, PhD, and Niels Boone, PharmD, argue that this result “apparently settles the case in favor of unrestricted switching of ‘expensive’ originator to ‘cheap’ biosimilar infliximab. Yet, the devil is the details.”

Van Bodegraven and Boone point out that the researchers reported that 26% of patients discontinued therapy within 1 year. Taken into consideration with the pre-switch 52-month use of infliximab, this percentage is high, and similar to the 30% flare rate seen in the NOR-SWITCH trial.³ The authors of the editorial state that, in many studies investigating switching, a 5% to 30% discontinuation rate have been documented, and that this phenomenon could be attributed to the so-called “nocebo” effect.

The nocebo effect refers to disease worsening due to negative expectations of a drug. Factors contributing to the nocebo effect include study design, therapeutic effectiveness, and patients’ and physicians’ expectancy and knowledge.

Van Bodegraven and Boone say that, from a patient perspective, after being prescribed an effective originator therapy, usually after having failed other therapies, switching from the originator drug provides no potential benefit, and a high nocebo percentage could induce loss of any potential economic gain resulting from switching. The authors also note that, although shared decision-making may help to reduce the nocebo effect, further documentation and investigation are necessary before making this conclusion.

In addition, the data derived from the switching study in question only investigated a single infliximab biosimilar. The authors say that studying only 1 biosimilar “Preclud[es] generalization to all registered biosimilars, not only due to compound-specific pharmacological differences, but also due to differences in registration practices ([eg], biosimilar trastuzumab was recently approved by the FDA, but the available data do not fulfil the [European Medicine Agency’s] approval requirements), and, even more importantly, due to potential harm to a patient’s well-being by a nocebo effect.”

References

1. Schmitz EMH, Boekema PJ, Straathof JWA, et al. Switching from infliximab innovator to biosimilar in patients with inflammatory bowel disease: a 12-month multicenter observational prospective cohort study. Aliment Pharmacol Ther. 2017;47(3):356-363. onlinelibrary.wiley.com/doi/10.1111/apt.14453/full. Published Deceber 5, 2017. Accessed February 26, 2018.

2. Van Bodegraven A, Boone N. Editorial: nocebo effect and switching to biosimilars. Aliment Pharmacol Ther. 2018;47(6):850-851. onlinelibrary.wiley.com/doi/10.1111/apt.14509/full Published February 15, 2018. Accessed February 26, 2018.

3. Jorgensen K, Olsen I, Goll G, et al. Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 53-week, randomized, double-blind, non-inferiority trial. Lancet. 2017;389(10086):2304-2316. thelancet.com/journals/lancet/article/PIIS0140-6736(17)30068-5/abstract.Published May 11, 2017. Accessed February 26, 2018.