Systematic Literature Review Shows Low Risk of Safety Concerns or Loss of Efficacy After Switching to a Biosimilar

In an effort to evaluate whether switching from a reference biologic to a biosimilar could lead to altered clinical outcomes—such as enhanced immunogenicity, compromised safety, or reduced efficacy—a research team, led by Hillel Cohen, PhD, conducted a systematic literature review of all available switching studies.
Kelly Davio
March 05, 2018
Despite the fact that no new safety or efficacy concerns have been detected in more than 10 years and 700 million patient days of experience with biosimilar medicines, some stakeholders remain cautious about switching from reference products to biosimilars, as they fear that such a switch could result in serious problems.

In an effort to evaluate whether switching from a reference biologic to a biosimilar could lead to altered clinical outcomes—such as enhanced immunogenicity, compromised safety, or reduced efficacy—a research team, led by Hillel Cohen, PhD, conducted a systematic literature review of all available switching studies.

The researchers searched Medline and Embase databases for switching studies up to June 30, 2017. Publications were considered if they contained efficacy or safety information on a switch from a reference drug to a biosimilar (studies that considered switches from erythropoietin to darbepoetin, erythropoietin to pegylated-erythropoietin, and insulin to insulin were not included).

In total, the researchers arrived at 90 studies that enrolled 14,225 unique individuals and that contained primary switching data. The studies included 7 molecular entities used to treat 17 disease indications. Most studies enrolled between 30 and 60 subjects.

Safety, Efficacy, and Immunogenicity
Thirty-six publications provided primary data describing the efficacy of large biologics (those with proteins 200 amino acids in length or larger, including etanercept, adalimumab, infliximab, and rituximab) after switching to biosimilars.

Among these publications, 12 were single-arm studies describing patients whose treatment was switched, and 24 were cohort studies comparing patients who switched with patients who did not. “Sporadic observations of loss of responses were reported in a few studies,” say the authors, though consistent patterns were observed.

Of switching articles examined, 39 reported treatment-emergent adverse events (TEAEs) and serious TEAEs. In 32% of these, serious TEAEs were reported as “nil” or 0%.

Anti-drug antibodies (ADAs) were assessed in 24 studies considering larger biosimilars, and 7 provided information on neutralizing antibodies (NABs). Thirteen studies assessed ADAs—4 addressed NABs—among the smaller biosimilars (erythropoietin, filgrastim, human growth hormone). “In all studies reporting immunogenicity data, ADA and NAB levels were found to be comparable at baseline and at the end of study across all disease indications and treatment groups,” say the authors.

One report raised safety concerns after switching from reference infliximab to a biosimilar; a study reviewing a Turkish claims database showed an 82% dropout rate (among 148 switched patients) versus a 24% dropout rate in a control group who remained on the reference product. The authors state that it is possible that these were chance results.

The authors further break down evidence from biosimilar switching studies by indication:



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