Is there a reason for concern or is it just hype? – A systematic literature review of the clinical consequences of switching from originator biologics to biosimilars

Abstract

While prescribing biosimilars to patients naive to a biologic treatment is a well-accepted practice, switching clinically stable patients from an originator to a biosimilar is an issue for clinicians. Well-designed clinical trials and real-world data which study the consequences of switching from an originator biologic treatment to its biosimilar alternative are limited, especially for monoclonal antibodies. Areas covered: A systematic literature review was conducted on PubMed to identify evidence of the consequences of switching from original biologics to biosimilars. References of included papers were also scrutinized. After a title-, abstract- and full text screening, out of the 153 original hits and 77 additional ones from screening the references, 58 papers (12 empirical papers, 5 systematic reviews and 41 non-empirical papers) were included. Expert opinion: Preventing patients on biologic medicines from switching to biosimilars due to anticipated risks seems to be disproportional compared to the expected cost savings and/or improved patient access. Indeed, it is the opinion of the authors that the concern of switching to biosimilars is overhyped.

Phase III randomized study of the proposed adalimumab biosimilar GP2017 in psoriasis: impact of multiple switches

“…A biosimilar medicine can only be authorized if it has the same safety and efficacy profile as the reference medicine, and clinically relevant changes in treatment are not expected upon switching from the reference medicine to a biosimilar medicine (or vice versa) . Although prescribing biosimilars to biologic‐naive patients is well accepted, switching patients between reference and biosimilar medicines may be a concern for clinicians due to lack of clinical data and recommendations . Concerns surrounding switching to biosimilars include the possibility of increased immunogenicity, safety issues and even loss of efficacy …”

“…As authority‐approved biosimilars and their reference medicines contain essentially the same active substance, it is reasonable to assume that there will be no difference in how a patient's immune system reacts to the two medicines upon switching . Nevertheless, the risk of enhanced hypersensitivity or anaphylactic reactions remains a key concern among physicians …”

Policy Practices to Maximise Social Benefit from Biosimilars

“…Overall, the opportunity cost of not switching patients to biosimilar medicines is greater in lower income than higher income countries, as health care budgets are more limited. Current evidence suggests that a single switch of patients treated with original biologic to biosimilar products after patent expiry is not associated with increased risk of adverse reactions or loss of efficacy [30][31][32][33]. When there is clinical trial or registry based evidence about continued efficacy and nonincreased adverse event rate after switching of a biological medicine to its biosimilar alternative, expedited review with CMA is sufficient to select the most cost-effective treatment strategy.…”

“…Additionally, debate on immunogenicity has been fuelled by manufacturers of original biologic medicines [29]. Recently, however, several systematic reviews evaluated the clinical consequences of switching to biosimilar medicines, but none of them concluded increased risk of adverse events or efficacy loss [30][31][32][33]. These reviews, along with evidence generated from recent clinical trials indicate that significant and quantifiable economic benefits from switching patients on maintenance biologic medicines to their biosimilar alternatives under medical supervision should not be sacrificed for non-quantifiable and fairly low risks of immunogenicity.…”

Prescribing biosimilars

“…A systematic review of 58 studies, including 12 clinical trials, mostly involving infliximab or epoetins, suggested that the expected cost savings of switching outweighed the risks of harms 18. A later review of 57 studies, covering a wider range of compounds (infliximab and epoetins, but also adalimumab, etanercept, filgrastim, follicle stimulating hormone, genotropin, insulin glargine, and rituximab), reported that safety and efficacy were mostly unchanged after switching 19.…”