Data Support Safety, Effectiveness of Biosimilar-to-Biosimilar Switching

As an increasing number of biosimilars for the same reference product becomes available, biosimilar-to-switching biosimilar is becoming more likely. A systematic review of studies on such switching has found the practice is safe and effective in clinical practice. The findins were published in BioDrugs.

There are currently 36 biosimilars approved in the United States. Of those on the market, trastuzumab and pegfilgrastim have the most biosimilars launched, with 5 each. In 2023, there will be at least 7 and as many as 11 adalimumab biosimilars launching in the United States.

Switching between a biosimilar and the reference product is often studied in randomized clinical trials, but biosimilar-to-biosimilar most often happens in the real world. Switching among biosimilars may be the result of insurance mandates, changes to formularies, or the patient relocating to a new region with different drug coverage.

“The possibility of multiple switches between biosimilars of the same reference biologic is already a reality, and these types of switches are expected to become more common in the future,” the authors wrote.

They undertook a systematic search using electronic databases to find publications as of December 2021 that evaluated effectiveness or safety data associated with switching between biosimilars. There were 982 citations. After removing duplicates and conducting a more thorough screening, 23 studies were evaluated. All of the studies were observation, and 13 were published in peer-reviewed journals; the remainder were published as abstracts.

The studies included 3657 patients. Overall, 17 studies and abstracts evaluated infliximab switching from Inflectra to Renflexis. Others evaluated switching between adalimumab biosimilars, etanercept biosimilars, and rituximab biosimilars.

Most of the infliximab switching studies were in inflammatory bowel disease (IBD). In IBD, patients experience a loss of response rate to the drug every year after the primary response, and studies found that loss of response rate for patients switching between biosimilars was similar to the rate for patients with IBD on any infliximab treatment.

The studies found that switching from the reference product to a biosimilar to another biosimilar had no impact on efficacy, immunogenicity, or safety. Patients who were transitioned from one biosimilar to another had no loss of disease control or safety concerns, according to one study.

Studies of infliximab for other indications found immunogenicity levels did not increase, there was no loss of disease control, and there was no increase in adverse events or hospitalizations as a result of biosimilar-to-biosimilar switching.

Studies of adalimumab biosimilar-to-biosimilar switching found no new safety or effectiveness concerns and that multiple switching did not decrease patient satisfaction.

The 2 etanercept biosimilar-to-biosimilar switching studies found safety and efficacy was maintained after switching, with no changes in disease activity or function.

There was only 1 study evaluating rituximab biosimilar-to-biosimilar switching, which assessed switching in patients with non-Hodgkin lymphoma and chronic lymphocytic leukemia. The study found that switching between biosimilars is not only safe but also does not lead to loss of efficacy.

The authors cautioned about conclusions made about biosimilar-to-biosimilar switching when only 1 or 2 studies were available. They also noted that all the studies included were observational studies, which are subjective and have the risk of individual researcher bias.

“It should be noted that since biosimilar-to-biosimilar switching is already occurring in some settings, additional data on this topic will likely become available in the future,” they wrote.

Reference

Cohen HP, Hachaichi S, Bodenmueller W, Kvien TK, Danese S, Blauvelt A. Switching from one biosimilar to another biosimilar of the same reference biologic: a systematic review of studies. BioDrugs. Published online July 6, 2022. doi:10.1007/s40259-022-00546-6