5 Things to Know About the Nocebo Effect and Biosimilars

The “nocebo” effect, a phenomenon that occurs when a patient’s negative perception of a therapy causes a treatment to have a worse outcome than would otherwise be expected, has become a topic of increasing interest in the world of biosimilars as some patients begin to transition from familiar, high-cost biologics to new, lower-cost biosimilars.

Here are 5 things to know about how the nocebo effect is impacting patients and other biosimilar stakeholders:

1. A recent study of Dutch patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis found that patients who were switched away from the anti—tumor necrosis factor (anti-TNF) agent Remicade (infliximab) to a cheaper biosimilar infliximab had a 24% discontinuation rate at 6 months. Researchers blamed the nocebo effect, calling the reasons for discontinuation “subjective.”

2. The nocebo effect is particularly vexing to industry. At a recent presentation at the SMi Biosimilars North America 2017 conference, Gary Cupit, PharmD, senior advisor to the investment bank Frontcourt Group, estimated that the nocebo effect could impact as many as 25% of patients. “It’s a common problem, and it’s getting worse…this is really becoming a statistical nightmare, trying to figure out how to break out those patients” in monitoring biosimilars’ safety and efficacy.

3. Counseling patients appears to be an effective way to counter the nocebo effect. Research presented at the American College of Rheumatology’s 2017 annual meeting in San Diego, California reported on a series of workshops in which patients with rheumatic diseases engaged with health care providers to develop personalized communications strategies related to switching. The researchers concluded that clear communication about the logistics of a must be provided, and that, in order to preserve patient engagement and empowerment, those whose therapy will be transitioned to a biosimilar must have ample opportunity to ask relevant questions.

4. However, not everyone agrees that the nocebo effect adequately explains the phenomenon of patients discontinuing biosimilar therapy. In a recent debate over switching patients with rheumatic diseases away from their brand-name biologics and onto biosimilar drugs, Roy Fleischmann, MD, pointed to discontinuation as a possible sign that switching to a biosimilar has caused a lost efficacy in a given patient. “Nocebo’s a word that comes up when you don’t get what you want to see,” he said. “[Do] you want to call it nocebo, or you want to call it the data?”

5. Emerging real-world experience suggests that the nocebo effect may not be to blame for patients’ discontinuation of biosimilars. A case study newly published in the European Journal of Rheumatology highlighted 3 patients with Behçet’s disease for whom a switch to biosimilar infliximab was associated with a rapid loss of treatment efficacy. All 3 patients required treatment with a different anti-TNF, adalimumab (Humira) to regain clinical remission.