HPE Biosimilars: Where are we and what is next? - Page 10


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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