Biological medicinal products contain active substances obtained from a biological source, such as live organisms or cells1. Biosimilars are medicinal products that are highly similar to already-marketed biological medicinal products, manufactured by different companies, using independently-developed cell lines and the companies’ own manufacturing processes.2
Although strict controls are put in place during manufacturing to ensure that minor differences do not affect the way in which the biosimilar acts or its safety2 there is uncertainty about whether switching from the reference medicine to a biosimilar could increase immunogenicity, compromise safety or diminish efficacy1.
In order to try and mitigate the uncertainty of doctors and patients, a group of biosimilar experts, led by Dr Hillel P. Cohen, has published a review of the studies conducted between 1993 and June 2017 in which a reference biological medicine was switched for its biosimilar.Their conclusions were published in March 2018 in the journal Drugs, which has been publishing original studies and reviews by world leaders in clinical research for more than 40 years3.
As part of their work, the authors performed a search on international databases, selecting articles on switching from reference biological medicines to their biosimilars. After a review of more than 2,000 articles and references, 90 were ultimately selected that met the inclusion criteria (sufficient scope, relevance, publication of the full text and unique research), involving 14,225 patients. The studies included data on seven biosimilars (infliximab, adalimumab, etanercept, epoetin, filgrastim, growth hormone and rituximab) used to treat 14 different diseases.
Data on arthritis1
Data on two infliximab biosimilars (CT-P13 and SB-2) in their approved indications (rheumatoid arthritis, ankylosing spondylitis and axial spondylitis, among others) were analysed. The studies did not reveal any significant differences in terms of efficacy or safety and immunogenicity was comparable to that of the reference biological medicine. One of the studies showed a drop-out rate of 16%, similar to the historic data on the reference biological medicine.
Data on inflammatory bowel disease1
The data comes from post-marketing studies of CT-P13, which analysed the differences in efficacy and safety in patients who continued to take the reference biological medicine and those who switched to the biosimilar. Both parameters were comparable, with no significant differences.
Data on psoriasis1
Psoriasis is considered a good indicator for evaluating biosimilars as the skin responds relatively quickly, with visible results that are easily quantifiable. Studies involving etanercept in moderate-to-severe plaque psoriasis, with up to three changes between biosimilars and their reference medicinal products, were analysed. Again, the efficacy, safety and immunogenicity of the biosimilar were comparable to the reference biological medicine.
In the studies involving adalimumab, there were no increases in adverse effects or in immunogenicity.
Other biosimilars and indications1
In a smaller number of studies conducted involving biosimilars of erythropoietin, filgrastim and growth hormone in a wide range of indications, similar efficacy and safety to the reference medicinal product was also observed.
In conclusion, it can be seen that there is a significant body of work that evaluates the impact on efficacy, safety and immunogenicity of switching from a reference biological medicine to its biosimilar. The data suggest that switching involves no risk and that patients and doctors have no reason to assume it will be problematic1, thereby fully endorsing the prescription of biosimilars.
As with any biological medicine, pharmacovigilance continues to allow us to monitor the emergence of new data and build up the confidence of patients and healthcare professionals, increasing the acceptance of these safe and effective medicinal products1.
- Cohen HP, Blauvelt A, Rifkin RM, Danese S, Gokhale SB, Woollett G. Switching Reference Medicines to Biosimilars: A Systematic Literature Review of Clinical Outcomes. Drugs. 2018;78(4):463–478. doi:10.1007/s40265-018-0881-y.
- Biosimilars in the EU, Information guide for healt.pdf.
- Drugs.S. Karger; 1971.