HPE Biosimilars: Where are we and what is next? - Page 23

expected and seen at both the clinical and economic levels , as well as in terms of quality of life . 1 , 2
Efficacy and adherence Biosimilars are approved by regulatory agencies on the basis that they are ‘ similar ’ to the reference product in terms of physicochemical properties , pharmacokinetic and pharmacodynamic profile , and efficacy and safety , which must be demonstrated in dedicated studies involving patients with immune-mediated inflammatory diseases . In the long-term the use of biologics and biosimilars may also contribute to the reduction of the rate of comorbidities and hospitalisations , and expensive medical procedures . 2 4
Patients with autoimmune diseases often experience pain and can present progressive deterioration of their physical and / or mental condition , leading to loss of ability to work and to perform daily living activities , which can , in turn , contribute to the development of depressive and anxiety disorders . From the societal point of view , the long treatment duration for these chronic diseases is often associated with high direct costs , but several studies have shown that the use of biologics and of biosimilars improves symptomatology , work productivity , and healthrelated quality of life . 2
However , patients switching to biosimilars may actually feel that their symptoms worsen and experience pain-related side effects ( the nocebo effect ), which may negatively affect patient adherence to treatment . Patient surveys have shown that concerns about safety and lack of efficacy are common , and high rates of discontinuation may in fact be observed after switching from the reference product ; hence negative perceptions about biosimilars need to be addressed as part of any treatment plan . 3
One known side effect of biologic agents ( particularly mAbs ) is their immunogenicity ( that is , the capacity to elicit an immune response that results in the production of antibodies against the medicine itself ), which may ultimately result in reduced clinical efficacy through increased clearance and reduced serum levels of the biologic , and increased risk of adverse events . Product-specific factors such as structure , use of concomitant therapies , and continuous vs . intermittent administration can influence immunogenicity in addition to patient predisposition and presence of active disease or comorbidities . When this immune reaction occurs , switching patients from a biologic to its biosimilar ‘ copy ’ due to a weak response to treatment caused by antibody production is not successful . 1 , 5
The comparability analysis of a biosimilar includes measuring the immunogenic potential of the molecule , which can be challenging owing to the absence of standardised criteria for assay sensitivity , and switching studies should demonstrate the absence of new immunogenic reactions with the biosimilar product . Despite initial concerns about potential differences in immunogenicity derived from structural and physicochemical differences between biosimilars and originators , the evidence shows similar immunogenicity , or less immunogenicity in some cases , for biosimilars used to treat immune-mediated inflammatory diseases . 3 , 5
Impact on health care expenditures and patient access Even in wealthy countries , budget restrictions may limit the utilisation of biologics for many
References 1 Feldman SR et al . Biosimilars for immune-mediated chronic diseases in primary care : What a practicing physician needs to know . Am J Med Sci 2018 ; 355 ( 5 ): 411 – 17 . 2 Baumgart DC et al . Biological therapies in immune-mediated inflammatory diseases : Can biosimilars reduce access inequities ? Frontiers Pharm 2019 ; 19 ( article 279 ): 1 – 13 . 3 Smolen JS et al . Era of biosimilars in rheumatology : reshaping the healthcare environment . RMD Open 2019 ; 5 : e000900 . 4 Wiland P et al . Biosimilar switiching – current state of knowledge . Reumatologia 2018 ; 56 ( 4 ): 234 – 42 . 5 Strand V et al . Immunogenicity of biologics in chronic inflammatory diseases . BioDrugs 2017:31:299 – 316 . 6 Hastier-De Chelle A et al . Impact of patient education on switch acceptance in IBD patients in remission , with infliximab originator switched for an infliximab biosimilar : A prospective study . Gastroenterology 2019 ; 156 ( 6 Suppl 1 ): S955 – 6 . patients , despite their clinical benefits and the recommendations of international scientific societies . Moreover , patients have high copayments for these medicines in some countries , which further contributes to an unequal access to treatment , and disparities in access can be influenced by national reimbursement policies and local prescription practices . For this reason , the implementation of biosimilars has aroused great interest , because it was expected that an increasingly competitive market would drive down the acquisition costs of these medicines , not only for biosimilar themselves , but also for other biologics in the same therapeutic class . 1 , 2
In fact , several budget impact models have predicted substantial savings with the implementation of biosimilars for inflammatory diseases , and these savings can potentially be applied to improve patient access or care in other therapeutic areas . For example , in Norway substantial price reductions ( up to 65 % versus the reference product ) have been negotiated for biosimilar infliximab through tender processes , whereas in the UK the prices of infliximab and etanercept dropped once lower-priced biosimilars were introduced despite a lower utilisation of the brand drugs . 2
The role of patient education While it is now universally accepted that naïve patients starting a new biologic should receive a biosimilar , the issue of switching ongoing treatments remains poorly defined . Although many countries in Europe allow the substitution of a biologic with its biosimilar at the pharmacy level , patients should be informed and feel comfortable with this switch . Individual patient characteristics such as age and education level may affect the likelihood of initiating and continuing treatment with biosimilars ; therefore it is of utmost importance that health care providers educate their patients , as well as themselves , about their safe use and potential concerns relative to their originators . 1 , 2 Two open-label studies indicated that strategies used to communicate a non-mandatory switch to biosimilar to patients with rheumatic diseases had a positive impact on discontinuation rates ; 3 a third prospective study involving patients with inflammatory bowel disease in remission showed that the switch acceptance rate increased for those who participated in an educational session about biosimilars . 6
As access to biosimilars expands , more data about switching from a reference product to a biosimilar , or between biosimilars of the same originator , will be obtained through registries and long-term observational studies . Careful monitoring following a switch is critical , and patients should be fully involved in the therapeutic decision-making process in order to improve clinical outcomes . 4
Conclusions Reining in the health care expenditures with biologics for chronic immune-mediated disorders is crucial to ensure that patients receive the best equitable care possible . Effectively promoting the use of biosimilars involves raising awareness of their overall benefits to society among health care providers and patients , but also introducing infrastructure changes to enable an efficient supply of medicines and implementing policies to improve the referral process and create economic incentives .
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