Decision making in prescribing and switching biosimilars
Switching from an originator to biosimilar should be managed at the discretion of the individual prescriber in shared partnership with the patient , with appropriate monitoring and education initiatives in place
Alain Astier PharmD PhD Honorary Head of the Department of Pharmacy Henri Mondor University Hospitals , Creteil , France ; Member of the French Academy of Pharmacy and of the Belgian Royal Academy of Medicine
From a logical and scientific point of view , the use of biosimilars should be widespread . Indeed , in Europe , the quality of biosimilars available on the market is very high as they are subject to full assessment by the European Medicines Agency ( EMA ) during the pre-marketing authorisation process . The current dogma states that totality of evidence must be developed by the manufacturer , including physico-chemical characteristics , preclinical data ( including in vitro mechanisms ) and clinical data . Indeed , these parameters – the critical quality attributes ( of which there are about 200 ) that are tested for a biosimilar candidate – must fall in the range of variability of the reference product , and determined on several batches . This set of rigorous analytical and preclinical methods thus demonstrates that the active moieties in the two products are ‘ highly similar ’.
Therefore , the pharmacological action and tolerance will be identical if a patient receives a biosimilar instead of the reference product , and also after switching ( interchanging ) drugs . 1 This is according to the basis of pharmacology established in the 19th century by the French physiologist , Claude Bernard : “ The same molecules will have the same action ”. 2 However , and surprisingly , this fundamental principle , which is a pillar of modern evidence-based medicine , is poorly understood , even by prescribers who should be applying this principle in their daily practice . A survey on biosimilars among oncologists revealed that only 69 % believed that a biosimilar had similar efficacy to a biologic ; 62 % agreed that the safety was equivalent , but only 12 % understood the rules and regulations for extrapolation . 3 Approximately 30 % of the panel did not believe comparable efficacy and tolerability , so it is peculiar that of the two-thirds who agreed , such a small percentage understood the direct relation between these and factors such as as safe extrapolation and switching .
This shows that perceptions can be governed by behavioural economics . Behavioural economics is a discipline that combines insights from psychology , economics , judgment , and decision-making , to better understand , predict , and potentially change human behaviour . 4 Indeed , people are often ‘ irrational economic actors ’. The theory proposes that such irrational behaviour relies on a limited number of heuristic principles , which reduce the complex intellectual tasks of assessing probabilities and predicting values to simplified judgment operations .
The same can be said of patients . A study has shown that nearly 25 % of patients with autoimmune diseases ( rheumatoid arthritis , psoriatic arthritis , ankylosing spondylitis ) receiving infliximab discontinued biosimilar treatment when switched from the originator , reporting worsened subjective symptoms . 5 This clearly demonstrates a nocebo effect , which is augmented by the fact that the switch was perceived to be dictated by economic reasons only , and the poor ability of the prescriber to explain the decision to the patient . Different mechanisms might play a part in the nocebo response including patient-related factors ( such as level of education ), psychosocial context , neurobiological factors and patients ’ negative expectations – the most studied and understood mechanism . The main sources of negative expectation-generated nocebo effects are the list of adverse events in the informed consent and the patients ’ negative opinions on biosimilars . In cases of switching , the patient must give his / her informed consent , and it is obvious that if the prescriber does not understand that biosimilars are as active and as safe as the originator drug , then he / she cannot objectively convince the patient .
The EMA defers to individual countries to decide whether to allow interchangeable use and substitution of the reference biologic and the biosimilar . The literature clearly demonstrates that switching between originators and biosimilars in real life makes no difference in terms of efficacy and tolerance . As an example , the NOR-SWITCH trial showed that switching from infliximab originator to CT-P13 , a biosimilar authorised in Europe , was not inferior to continued treatment with infliximab originator in rheumatology indications . 6 Very recently , the NOR-SWITCH extension study showed no difference in safety and efficacy between patients who continued treatment with infliximab biosimilar ( CT-P13 ) and patients who switched from the originator infliximab to CT-P13 , supporting the idea that switching from originator infliximab to CT-P13 is safe and efficacious . 7 Many review papers also demonstrate the safety of switching for a number of other biosimilars , such as insulin . 8 – 10
The view of safe interchangeability has been endorsed by numerous medicines agencies and scientific societies , particularly the European Society of Medical Oncology . 11 – 14 Interchangeability includes switching and substitution ( switching is decided by the prescriber while substitution is done at the pharmacy level ). Indeed , if interchangeability is accepted by medical organisations , it is always emphasised that only the prescriber must decide . From a logical point of view , this stance can be criticised . Indeed , a biosimilar is fully comparable in all aspects to its originator , so there is no
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