In this infancy period of biosimilar access in the US, reference manufacturers, prescribers, and some patient advocacy groups have stirred the notion that biosimilars are not as safe and effective as their reference products. The 13 years of experience in Europe, clinical data produced by biosimilar manufacturers, and approvals by the US Food and Drug Administration represent ongoing efforts to put that negative comparison to rest. Yet, the so-called “nocebo effect” has not been well investigated in patients taking biosimilars. An article by researchers from the University of North Carolina Medical Center published today finds some evidence of this biosimilar nocebo effect in open-label clinical trials.
The biosimilar nocebo effect occurs when a patient taking a drug biosimilar to experience some adverse events or poor results and these negative outcomes (e.g., perceived lack of efficacy or adverse events) actually occur. In comparison, the placebo effect occurs when patients experience improved outcomes though they are taking inactive medications (that they believe to be active).
The authors of the study, which was published in the Journal of Managed Care and Specialty Pharmacy, conducted a literature review of studies involving a switch from a reference product to a biosimilar product. Clinical trials of biosimilar and reference biologics included adalimumab, bevacizumab, etanercept, and infliximab. The key focus was a comparison of open-label investigations (where the patients were aware they were receiving a biosimilar) and blinded studies (when they were not given information as to their treatment).
The researchers found that all-cause discontinuation rates were double that in open-label investigations compared with double-blinded studies (median, 14.3% vs. 6.95%, respectively). This relationship was found when discontinuation was caused by adverse drug events (median, 5.6% vs. 3.1%, respectively).
In this analysis of the biosimilar nocebo effect, greatest number of studies involved infliximab biosimilars and Remicade®. When evaluating these investigations only, the researchers found that the development of antidrug antibodies and infusion-site reactions were similar between the open-label and double-blinded studies. However, the all-cause discontinuation rates were notably higher in open-label versus double-blinded studies.
Although this evidence suggests that a biosimilar nocebo effect may be present, the authors state that further studies are needed to conclude its existence.
