In explaining why some patients who switch to biosimilars from reference biologics discontinue their therapy at a higher rate than those who remain on a therapy without interruption, some authors have referenced the so-called “nocebo” effect. This effect, whereby a patient experiences disease worsening or adverse events due to negative beliefs about a drug, has been controversial, however, and not all clinicians agree that the effect is to blame for differences in discontinuation.
In explaining why some patients who switch to biosimilars from reference biologics discontinue their therapy at a higher rate than those who remain on a therapy without interruption, some authors have referenced the so-called “nocebo” effect. This effect, whereby a patient experiences disease worsening or adverse events (AEs) due to negative beliefs about a drug, has been controversial, however, and not all clinicians agree that the effect is to blame for differences in discontinuation.
Read more about the nocebo effect and biosimilars.
A newly published review sought to investigate the nocebo effect; the review’s authors assessed studies reporting the efficacy and safety outcomes of a switch from a reference drug to an FDA-approved biosimilar. A total of 31 trials were included; 28 involved infliximab, and 3 involved etanercept. Among these studies, only 2 studies of infliximab were double-blinded randomized controlled trials (RCTs), and 2 publications on etanercept evaluated different time points of the same double-blinded RCT.
Results for 3271 patients were reported in total. The most common indications for treatment were inflammatory bowel disease, rheumatoid arthritis, and psoriasis. The mean followup after a switch to a biosimilar was 48 weeks (range, 16-80 weeks).
The analysis revealed that the median discontinuation rates for any reason were 14.3% in open-label studies (range, 0.0%-33.3%) versus 6.95% in double-blinded RCTs (range, 5.2%-11.0%). Discontinuation rates resulting from AEs were 5.6% in open-label studies (range, 0.0%-24.2%) versus 3.1% (range, 2.0%-5.2%) in double-blinded RCTs. A subgroup analysis revealed that antidrug antibody development and infusion reactions were similar between patients in open-label and double-blind RCTs of infliximab.
“Some evidence from the comparison of biosimilar discontinuation rates supports the hypothesis that this outcome measure is highly susceptible to the nocebo effect,” write the authors, but they add that “current evidence is insufficient to confirm a biosimilar nocebo effect.” More studies will be needed to evaluate whether the nocebo effect does in fact impact patients who switch to biosimilars and to identify mitigation strategies—such as patient education—that could help to overcome such an effect.
However, the authors point out that provider education may well play a role in mitigating a nocebo effect, if indeed it is present. Physicians’ knowledge gaps around biosimilars or hesitancy to use these agents may either create or reinforce patients’ negative expectations, so appropriate framing of discussions about biosimilars will be key.
Reference
Odinet JS, Day CE, Cruz JL, Heindel GA. The biosimilar nocebo effect? A systematic review of double-blinded versus open-label studies. J Manag Care Spec Pharm. 2018;24(10):952-959. doi: 10.18553/jmcp.2018.24.10.952.
Study Documents HCPs’ Experiences of a Mandatory Switch to Inform Future Transitions
December 2nd 2023A survey explores the experiences of health care providers (HCP) throughout the transition process following a mandatory switch from the adalimumab originator (Humira) to a biosimilar in New Zealand in 2022.
What AmerisourceBergen's Report Reveals About Payers, Biosimilar Pricing Trends
May 28th 2023On this episode of Not So Different, Tasmina Hydery and Brian Biehn from AmerisourceBergen discussed results from a recent survey, that were also presented at Asembia 2023, diving into the payer perspective on biosimilars and current pricing trends across the US biosimilar industry.
HHS Praises Biosimilars Savings but Opportunities to Reduce Part B Spending Remain
November 28th 2023Although biosimilars have already generated savings for Medicare Part B programs and beneficiaries, opportunities for substantial reductions in spending remain, according to a report from the HHS.
Pipelines and Preparation: How the US Can Prepare for More RA Biosimilars
April 16th 2023What can practices do to prepare for all the biosimilars to treat rheumatoid arthritis (RA) coming down the pipeline? And how can they ensure that the lower-than-anticipated adoption rates for infliximab biosimilars are not repeated? Robert Zutaut, RPh, from McKesson Provider Solutions, tackles all this and more on this episode of Not So Different.
Study: Biosimilar Use, Dose Rounding Produce More Cost Savings Than Either Strategy Alone
November 18th 2023A retrospective study of New England patients receiving trastuzumab or bevacizumab found that combining dose rounding and biosimilar use resulted in greater cost savings than either strategy alone.
Part 3: Study Questions Usefulness of Clinical Efficacy Trials for Oncology Biosimilars in Europe
November 16th 2023In part 3 of a 3-part series for Global Biosimilars Week, The Center for Biosimilars® reviews an analysis investigating whether clinical efficacy studies have an impact on prescribing decisions for oncology biosimilars across Europe.