Opinion: Incorporate Nocebo Planning Into IBD Treatment Strategy

The nocebo effect is real and documented, and in inflammatory bowel disease (IBD) it’s important to plan interventions early in the treatment cycle to head off psychological rejection of biosimilars, according to authors of an opinion piece.

“The nocebo effect is defined as a negative effect of a pharmacological or nonpharmacological medical treatment that is induced by patients’ expectations and that is unrelated to the physiological action of the treatment,” the authors wrote.

Patients with ulcerative colitis and Crohn disease are vulnerable to depression (40.1%) and anxiety disorders (30.6%) and are highly sensitive to perceived consequences of switching to biosimilars which, although equal in safety and efficacy to originator products, may not inspire the same confidence that patients derive from established brands, they wrote.

They said physicians and other health care professionals can play a significant role in developing trust and a sense of security in patients for the use of biosimilars, and this in turn can reduce biosimilar rejection and improve outcomes, and thereby contribute to the value proposition that lower cost biosimilars have to offer. They also recommended that mental health professionals be included in IBD management teams.

In the age of widely disseminated health information via the internet and social media, where patients can obtain incorrect information or be strongly influenced by opinions coming from non—health professional sources, how these influences may contribute to the nocebo effect cannot be ignored, they said.

“The nocebo effect might prevent the widespread uptake of biosimilars, ultimately undermining the positive cost-saving effects,” the authors wrote. In their review they summarized much recent evidence on the nocebo effect with an eye toward providing up-to-date guidance for health care professionals.

Many things can contribute to the development of the nocebo effect. The authors noted that patients who have experienced adverse events with an originator therapy will be more likely to experience the nocebo effect, and so an upfront explanation by a physician who is familiar with biosimilars and can explain their value and safety and efficacy can make a huge difference in whether patients accept and adhere to biosimilar treatment, the authors said.

“Awareness of nocebo phenomenon is of paramount importance, since IBD patients commonly report fear of drug-related side effects, and high nocebo percentages are expected in chronic conditions characterized by recurrence of symptoms, such as ulcerative colitis and Crohn disease,” they wrote.

Among many examples they cited, the authors noted a European study of patients with IBD (n = 1181) whose findings indicated 38.6% of patients were worried about the safety profile of biosimilars. A 1-year pragmatic study to assess the incidence of nocebo effect in patients who switched from infliximab originator to an infliximab biosimilar found no significant statistical change in disease activity or biomarkers for those treated with originator vs biosimilar infliximab, but demonstrated an overall nocebo rate of 12.9% in patients with IBD. Nocebo in this study was defined as an unexplained, unfavorable therapeutic response following a switch to a biosimilar, followed by a beneficial effect after the innovator drug was resumed.

In another study, patients with IBD were given an interview with a gastroenterologist during which information on biosimilars’ efficacy and safety were explained to patients, and follow-up information was provided, and it was observed via survey that the interview “changed the opinion on biosimilars in about two-thirds of respondents (64.7%) and in 60% of cases influenced the decision to switch” to biosimilars.”

The authors concluded, “Obviously, a detailed physician’s knowledge of efficacy and safety of biosimilars and nocebo effect is an indispensable requirement for an effective communication.”

Further, they recommended efforts be made to identify patients most at risk for the nocebo effect, which they suggested could be achieved via the use of tools such as The Perceived Sensitivity to Medicines score, a 5-item checklist that investigates perceived sensitivity or “super-reaction” to medicines and previous drug reactions.

Reference

D’Amico F, Solitano V, Peyrin-Biroulet L, Danese S. Nocebo effect and biosimilars in inflammatory bowel diseases: what’s new and what’s next? Expert Opin Biol Ther. Published online August 28, 2020. doi:10.1080/14712598.2020.1817374