Beyond Cost: Observations on Clinical and Patient Benefits of Biosimilars in Real-World Settings

Abstract

The introduction of biosimilars into healthcare systems globally is recognized by many as a healthcare success. Despite this, questions have been raised about whether biosimilars can deliver sufficient value to patients and healthcare professionals, as well as sufficient cost saving, for their use in treatment to be worthwhile. In this review, we discuss how the increasing financial burden of complex therapeutic medicines, such as biologics, can be ameliorated by off-patent biosimilar medicines, particularly with increasing worldwide incidences of cancer and other chronic diseases. We then describe real-world cases that demonstrate the significant direct and indirect benefits of biosimilars to patients and healthcare systems beyond costs. Healthcare sustainability is crucial to ensuring that healthcare systems can continue to deliver high-quality care to patients. The savings realized from the introduction of biosimilars have expanded treatment options and improved access to therapies across a spectrum of diseases. Cost savings from biosimilar use have also led to changes in treatment guidelines, increasing the availability of biologic medicines for earlier lines of therapy. This expansion of access can have a positive impact on the overall patient experience and can reduce the overall disease burden. However, the adoption of biosimilars has not been universally successful, and faces challenges in the current healthcare landscape and in the pharmaceutical development pipeline.

Key Points

Increased availability of biosimilars reduces the financial burden on healthcare systems globally, leading to greater and more timely access to therapy for patients; in turn, this can lead to improved clinical outcomes and reduced overall disease burden.

Adoption of biosimilars has been encouraged in various countries through the implementation of clinical guideline updates and benefit sharing schemes for savings realized.

Introduction

Biosimilars have been hailed as a pharmaceutical success, demonstrating that large, complex, protein molecules can be developed and manufactured as high-quality off-patent medicines, with equivalent efficacy and similar safety profiles to their reference biologics [1, 2]. However, there have been doubts over whether biosimilars can deliver benefits in terms of budgets and patient access for multiple stakeholders, and sufficient cost saving to make their adoption worthwhile. This is because the overall value of biosimilar medicines is sometimes seen as low when balanced against the effort required to change entrenched prescribing and procurement habits [3, 4].

The aim of this review is to describe real-world case examples, with a focus on oncology and immune-mediated inflammatory diseases, demonstrating the significant value of biosimilars to societies at large, in terms of lowering biologic costs and increasing patient access to biologics. This review focuses on: (1) the direct and indirect benefits of biosimilars to patients; and (2) the benefits of biosimilars to healthcare systems. We include a discussion on the possible contribution of biosimilars to healthcare systems, including direct cost savings or avoidance of unnecessary excess costs to help improve healthcare sustainability and accessibility.

Methods

A narrative literature search was conducted on 13 July 2023. The MEDLINE database was searched using the following search terms: biosimilar AND access OR benefit OR capacity OR cost OR finan* OR nurse OR outcome OR value OR saving OR sustain*, with results limited to 2010–2023. Manual searches of abstracts from the European Crohn’s and Colitis Organisation, European Alliance of Associations for Rheumatology, European Association of Hospital Pharmacists, European Academy of Dermatology and Venereology, American Society of Clinical Oncology, and European Society of Medical Oncology congresses were performed and limited to January 2020–December 2023.

Retrieved articles were reviewed for relevance based on their titles and abstracts. Articles were selected for inclusion if they reported data from real-world studies in oncology (any hematological malignancy) or immune-mediated inflammatory diseases (Crohn’s disease, ulcerative colitis, ankylosing spondylitis, axial spondyloarthritis, psoriasis, psoriatic arthritis, and rheumatoid arthritis [RA]) in any region worldwide. Additional references, restricted to adult cases, were identified from the bibliographies of retrieved articles, further targeted searches, and the authors’ own expertise and local knowledge.

Current Status of Biosimilars

The increasing use of high-cost biologics has placed a heavy financial burden on healthcare systems [5]. In 2023, biologics accounted for 40% (€87.6 billion) of the total spending on medicines in the European Union, and this is forecast to continue increasing [6]. In the USA, biologics account for 38‒40% of all pharmaceutical spending [7, 8]. This burden is likely to be further impacted by anticipated increases in the incidence of chronic diseases and cancer, largely driven by population growth and ageing [9–11], as well as by the introduction of new therapies with novel mechanisms of action (MoAs). In many countries, access to biologics is limited and some patients may be prevented from receiving prompt treatment, less likely to receive optimal doses, or continue with appropriate therapies, than in other countries [12].

Healthcare sustainability is essential to ensure that health services can continue to deliver high-quality care, both now and in the future [13]. Biosimilars sustain the benefits of biologic therapy whilst also delivering substantial cost savings, thereby increasing the affordability of biologics, and improving access, as well as contributing to the sustainability of healthcare systems [5, 14]. Cost savings generated by biosimilars can also be used to increase access to new, innovative molecules for broader patient populations [15]. In addition, they can help optimize treatment pathways, provide value-added services to support patient care, and enable reinvestment in new research [16].

From the approval of the first biosimilar in 2006, the European Medicines Agency (EMA) has recommended the approval of 106 biosimilars, whereas 72 have been licensed by the United States Food and Drug Administration (FDA) across various drug classes and indications (as of April 2025; Table 1) [17, 18]. Many other biosimilars are currently in clinical development or undergoing regulatory assessment (Table 2).

Table 1.

Overview of biosimilars approved by the European Medicines Agency and the United States Food and Drug Administration [17, 18, 94, 95]

Active substance: Therapy area(s)	Manufacturer	Biosimilars approved in Europe (n = 106)		Biosimilars approved in the USA (n = 72)
		Product name	Authorization date	Product name	Authorization date
Adalimumab: Immune-mediated inflammatory diseases	Amgen	Amgevita	21 Mar 2017	Abrilada (adalimumab-afzb)	15 Nov 2019
	Boehringer Ingelheim			Cyltezo (adalimumab-adbm)	25 Aug 2017, 15 Oct 2021
	Alvotech/Teva (USA) Stada Arzneimittel (Europe)	Hukyndra Libmyris	15 Nov 2021 12 Nov 2021	Simlandi (adalimumab-ryvk)	23 Feb 2024
	Celltrion	Yuflyma	11 Feb 2021	Yuflyma (adalimumab-aaty)	23 May 2023
	Coherus			Yusimry (adalimumab-aqvh)	17 Dec 2021
	Fresenius Kabi	Idacio	2 Apr 2019	Idacio (adalimumab-aacf)	14 Dec 2022
	Mylan/Fujifilm Kyowa Kirin Biologics	Hulio	17 Sep 2018	Hulio (adalimumab-fkjp)	6 Jul 2020
	Pfizer	Amsparity	13 Feb 2020	Amjevita (adalimumab-atto) Abrilada (adalimumab-afzb)	23 Sep 2016 15 Nov 2019
	Sandoz	Hyrimoz Hefiya	26 Jul 2018 26 Jul 2018	Hyrimoz (adalimumab-adaz)	30 Oct 2018
	Samsung Bioepis	Imraldi	24 Aug 2017	Hadlima (adalimumab-bwwd)	23 Jul 2019
Aflibercept: Retinopathy	Amgen			Pavblu (aflibercept-ayyh)	23 Aug 2024
	Biocon	Yesafili	15 Sep 2023	Yesafili (aflibercept-jbvf)	20 May 2024
	Celltrion	Eydenzelt	12 Feb 2025
	Formycon/Klinge Pharma	Ahzantive Baiama	13 Jan 2025 13 Jan 2025	Ahzantive (aflibercept-mrbb)	28 Jun 2024
	Sandoz	Afqlir	13 Nov 2024	Enzeevu (aflibercept-abzv)	9 Aug 2024
	Samsung Bioepis/Biogen	Opuviz	13 Nov 2024	Opuviz (aflibercept-yszy)	20 May 2024
Bevacizumab: Various cancers	Amgen/Allergan	Mvasi	15 Jan 2018	Mvasi (bevacizumab-awwb)	14 Sep 2017
	Amneal	Alymsys	26 Mar 2021	Alymsys (bevacizumab-maly)	13 Apr 2022
	Biocon	Abevmy	21 Apr 2021
	Celltrion	Vegzelma	17 Aug 2022	Vegzelma (bevacizumab-adcd)	27 Sep 2022
	Pfizer	Zirabev	14 Feb 2019	Zirabev (bevacizumab-bvzr)	27 Jun 2019
	Sandoz/Bio-Thera	Avzivi	26 Jul 2024	Avzivi (bevacizumab-tnin)	19 Dec 2023
	Samsung Bioepis	Aybintio	19 Aug 2020
	Stada Arzneimittel	Oyavas	26 Mar 2021
Denosumab: Osteoporosis, bone malignancies	Celltrion	Osenvelt Stoboclo	14 Feb 2025 14 Feb 2025	Osenvelt/Stoboclo (denosumab-bmwo)	28 Feb 2025
	Fresenius Kabi			Bomyntra/Conexxence (denosumab-bnht)	25 Mar 2025
	Samsung Bioepis	Obodence	2 Feb 2025	Ospomyv/Xbryk (denosumab-dssb)	13 Feb 2025
	Sandoz	Jubbonti Wyost	16 May 2024 17 May 2024	Jubbonti/Wyost (denosumab-bddz)	5 Mar 2024
Eculizumab: PNH, aHUS	Amgen	Bekemv	26 Apr 2023	Bekemv (eculizumab-aeeb)	28 May 2024
	Samsung Bioepis	Epysqli	26 May 2023	Epysqli (eculizumab-aagh)	19 Jul 2024
Enoxaparin sodium: Venous thromboembolism	Techdow Europe	Inhixa	15 Sep 2016
Epoetin alfa: Anemia	Medice Arzneimittel Pütter	Abseamed	28 Aug 2007	Retacrit (epoetin alfa-epbx)	15 May 2018
	Sandoz	Binocrit	28 Aug 2007
	Hexal	Epoetin alfa Hexal	27 Aug 2007
Epoetin zeta: Anemia	Hospira/Pfizer	Retacrit	18 Dec 2007
	Stada Arzneimittel	Silapo	18 Dec 2007
Etanercept: Immune-mediated inflammatory diseases	Mylan	Nepexto	25 May 2020
	Samsung Bioepis	Benepali	13 Jan 2016	Eticovo (etanercept-ykro)	25 Apr 2019
	Sandoz	Erelzi	23 Jun 2017	Erelzi (etanercept-szzs)	30 Aug 2016
Filgrastim: Neutropenia	Accord Healthcare	Accofil	18 Sep 2014
	Apotex	Grastofil	17 Oct 2013
	CuraTeQ	Zefylti	12 Feb 2025
	Hexal	Filgrastim Hexal	6 Feb 2009
	Hospira/Pfizer	Nivestim	7 Jun 2010	Nivestym (filgrastim-aafi)	20 Jul 2018
	Kashiv/Amneal			Releuko (filgrastim-ayow)	25 Feb 2022
	Ratiopharm	Ratiograstim	15 Sep 2008
	Tanvex			Nypozi (filgrastim-txid)	28 Jun 2024
	Teva	Tevagrastim	15 Sep 2008
	Sandoz	Zarzio	6 Feb 2009	Zarxio (filgrastim-sndz)	6 Mar 2015
Follitropin alfa: Anovulation (IVF)	Finox Biotech	Bemfola	26 Mar 2014
	Teva	Ovaleap	27 Sep 2013
Infliximab: Immune-mediated inflammatory diseases	Amgen			Avsola (infliximab-axxq)	6 Dec 2019
	Celltrion	Remsima	10 Sep 2013	Zymfentra (infliximab-dyyb)	23 Oct 2023
	Hospira/Pfizer	Inflectra	10 Sep 2013	Inflectra (infliximab-dyyb)	5 Apr 2016
	Pfizer			Ixifi (infliximab-qbtx)	13 Dec 2017
	Samsung Bioepis/Merck	Flixabi	26 May 2016	Renflexis (infliximab-abda)	21 Apr 2017
	Sandoz	Zessly	18 May 2018
Insulin aspart: Diabetes	Sanofi-Aventis	Insulin aspart Sanofi	25 Jun 2020	Merilog (insulin aspart-szjj)	14 Feb 2025
	Biocon	Kirsty (formerly Kixelle)	5 Feb 2021
	Sanofi-Aventis	Truvelog Mix 30	25 Apr 2022
Insulin glargine: Diabetes	Biocon	Semglee	23 Mar 2018	Semglee (insulin glargine-yfgn)	11 Jun 2020, 28 Jul 2021
	Eli Lilly/Boehringer Ingelheim	Abasaglar	9 Sep 2014	Basaglar* Rezvoglar (insulin glargine-aglr)	16 Dec 2015 17 Dec 2021
Insulin lispro: Diabetes	Sanofi-Aventis	Insulin lispro	19 Jul 2017	Admelog*	11 Dec 2017
Natalizumab: Multiple sclerosis	Sandoz	Tyruko	22 Sep 2023	Tyruko (natalizumab-sztn)	24 Aug 2023
Omalizumab: Asthma, urticaria	Celltrion	Omlyclo	16 May 2024	Omlyclo (omalizumab-igec)	7 Mar 2025
Pegfilgrastim: Neutropenia	Accord	Pelgraz	21 Sep 2018
	Coherus			Udenyca (pegfilgrastim-cbqv)	2 Nov 2018
	Cinfa Biotech/Mundipharma	Pelmeg	20 Nov 2018
	Fresenius Kabi	Stimufend	28 Mar 2022	Stimufend (pegfilgrastim-fpgk)	6 Sep 2022
	Juta Pharma/USV	Grasustek	20 Jun 2019
	Kashiv/Amneal			Fylnetra (pegfilgrastim-pbbk)	26 May 2022
	Mundipharma Biologics	Cegfila (formerly Pegfilgrastim Mundipharma)	19 Dec 2019
	Biocon	Fulphila	20 Nov 2018	Fulphila (pegfilgrastim-jmdb)	4 Jun 2018
	Hospira/Pfizer	Nyvepria	18 Nov 2020	Nyvepria (pegfilgrastim-apgf)	10 Jun 2020
	Sandoz	Ziextenzo	22 Nov 2018	Ziextenzo (pegfilgrastim-bmez)	4 Nov 2019
Ranibizumab: Retinopathy	Bioeq/Teva Pharma	Ranivisio	25 Aug 2022
	Coherus/Sandoz			Cimerli (ranibizumab-eqrn)	2 Aug 2022
	Qilu Pharma	Rimmyrah	5 Jan 2024
	Midas Pharma	Ranibizumab Midas	19 Sep 2024
	Samsung Bioepis/Biogen	Byooviz	18 Aug 2021	Byooviz (ranibizumab-runa)	17 Sep 2021
	Stada Arzneimittel/Xbrane Biopharma	Ximluci	9 Nov 2022
Rituximab: Immune-mediated inflammatory diseases and hematological cancers	Amgen			Riabni (rituximab-arrx)	17 Dec 2020
	Celltrion/Teva	Blitzima Truxima	13 Jul 2017 17 Feb 2017	Truxima (rituximab-abbs)	28 Nov 2019
	Pfizer	Ruxience	1 Apr 2020	Ruxience (rituximab-pvvr)	23 Jul 2019
	Sandoz	Rixathon Riximyo	15 Jun 2017 15 Jun 2017
Somatropin: Growth hormone deficiency	Sandoz	Omnitrope	12 Apr 2006
Teriparatide: Osteoporosis	Accord	Sondelbay	24 Mar 2022
	Gedeon Richter	Terrosa	4 Jan 2017
	Theramex	Livogiva	27 Aug 2020
	Thornton & Ross, Stada	Movymia	11 Jan 2017
Tocilizumab: Immune-mediated inflammatory diseases	Biogen/BioThera	Tofidence	20 Jun 2024	Tofidence (tocilizumab-bavi)	29 Sep 2023
	Celltrion	Avtozma	14 Feb 2025	Avtozma (tocilizumab-anoh)	24 Jan 2025
	Fresenius Kabi	Tyenne	15 Sep 2023	Tyenne (tocilizumab-aazg)	5 Mar 2024
Trastuzumab: Breast and gastric cancers	Accord/Henlius	Zercepac	27 Jul 2020	Hercessi (trastuzumab-strf)	29 Apr 2024
	Amgen/Allergan	Kanjinti	16 May 2018	Kanjinti (trastuzumab-anns)	13 Jun 2019
	Celltrion/Teva	Herzuma	8 Feb 2018	Herzuma (trastuzumab-pkrb)	14 Dec 2018
	Biocon	Ogivri	12 Dec 2018	Ogivri (trastuzumab-dkst)	1 Dec 2017
	Pfizer	Trazimera	26 Jul 2018	Trazimera (trastuzumab-qyyp)	11 Mar 2019
	Prestige Biopharma	Tuznue	19 Sep 2024
	Samsung Bioepis	Ontruzant	15 Nov 2017
	Sandoz/EirGenix	Herwenda	15 Nov 2023
Ustekinumab: Immune-mediated inflammatory diseases	Accord	Absimky Imuldosa	12 Dec 2024 12 Dec 2024	Imuldosa (ustekinumab-srlf)	10 Oct 2024
	Alvotech/Stada/Teva	Uzpruvo	5 Jan 2024	Selarsdi (ustekinumab-aekn)	16 Apr 2024
	Amgen	Wezenla	20 Jun 2024	Wezlana (ustekinumab-auub)	21 Oct 2023
	Biocon	Yesintek	14 Feb 2025	Yesintek (ustekinumab-kfce)	29 Nov 2024
	Celltrion	Steqeyma	22 Aug 2024	Steqeyma (Ustekinumab-stba)	17 Dec 2024
	Fresenius Kabi/Formycon	Otulfi Fymskina	25 Sep 2024 25 Sep 2024	Otulfi (ustekinumab-aauz)	27 Sep 2024
	Samsung Bioepis/Sandoz	Pyzchiva Eksunbi	22 Apr 2024 12 Sep 2024	Pyzchiva (ustekinumab-ttwe)	28 Jun 2024

Data are current as of 2 April 2025, for European and US biosimilar approvals

aHUS atypical hemolytic uremic syndrome, IVF in vitro fertilization, PNH paroxysmal nocturnal hemoglobinuria

*Approved as a follow-on biological

Table 2.

Summary of biosimilars in phase III clinical development or undergoing regulatory review in the USA and Europe [94–96]

Molecule	Reference product	Manufacturer	Biosimilar
Aflibercept	Eylea	Alvotech	AVT06
		Celltrion	CT-P42
		Rophibio	RBS-001
		Sam Chun Dang	SCD411
Bevacizumab	Avastin	Prestige Biopharma	HD204
Denosumab	Xgeva/Prolia	Alvotech	AVT03
		Biocon	BMAB-1000
		Celltrion	CT-P41
		Eden Biologics	EB1001
		Enzene Biosciences	Enz215
		Fresenius Kabi	FKS518
		Gedeon Richter/Hikma	RGB-14
		Intas	Olimab
		Luye Pharma Group	LY06006/LY01001
		Organon	HLX14
		Samsung Bioepis	SB-16
		Teva	TVB-009
Epoetin alpha	Epogen/Procrit	Apotex	APO-EPO
Golimumab	Simponi	Bio-Thera Solutions	BAT2506
		Alvotech	AVT05
Infliximab	Remicade	Sagent	NI-071
Insulin aspart	Novolog	Amphastar	AMP-004
		Gan & Lee/Sandoz	Rapilin
Insulin glargine	Lantus/Basaglar	Gan & Lee/Sandoz	Basalin
Insulin lispro	Humalog	Gan & Lee/Sandoz	Prandilin
Natalizumab	Tysabri	Polpharma Biologics	PB006
Nivolumab	Opdivo	Amgen	ABP 206
		Sandoz	JPB898
Omalizumab	Xolair	Alvotech	AVT23
		Amneal/Kashiv	ADL-018
		Aurobindo	BP11
		Teva	TEV-45779
Pegfilgrastim	Neulasta	Accord/Apotex	Lapelga
		Lupin	Lupifil-P
Pembrolizumab	Keytruda	Amgen	ABP 234
		Bio-Thera	BAT3306
		Samsung Bioepis	SB27
		Sandoz	GME751
Pertuzumab	Perjeta	Organon	HLX11
Ranibizumab	Lucentis	Lupin	LUBT010
Rituximab	Rituxan	Dr Reddy’s	DRL RI
		Mabion	MabionCD20
Secukinumab	Cosentyx	Bio-Thera	BAT2306
		Celltrion	CT-P55
Tocilizumab	Actemra	Celltrion	CT-P47
		Dr Reddy’s	DRL_TC
Trastuzumab	Herceptin	Tanvex	TX05
Ustekinumab	Stelara	Bio-Thera Solutions	BAT2206
Vedolizumab	Entyvio	Alvotech/Teva	AVT16
		Polpharma	PB016

Data are limited to publicly disclosed information and may not reflect all biosimilars that are in clinical development or that are under regulatory review

What Has Been Achieved with Biosimilars

The introduction of biosimilars can result in savings through price competition with the reference product and between biosimilars, and can induce reference medicine manufacturers to lower their prices or offer discounts [19, 20]. These savings have the potential to expand treatment options and improve access to therapies for different diseases. This is especially true in patients who previously could not access biologics, for example, owing to out-of-pocket expenses. In various jurisdictions, patients gain access once a product is added to formulary; however, this access can be constrained by local approval criteria [5, 14–16].

While in many instances, treatment guidelines recommend prompt treatment with biologics, many patients do not receive them because of local access limitations; however, cost reductions from biosimilar use have expanded the treatment options available at earlier disease stages [21]. This can enable broader patient access to biologics generally and timely introduction of medicines that prevent disease complications arising, improving options for later treatment and, overall, improving patient quality of life [22, 23]. This may also save costs at the end of treatment, as the use of expensive second- and third-line therapies and disease complications can be avoided.

Biosimilars also offer indirect patient benefits, for example, by contributing to surety of supply. Biologic medicines are complex and have specialized manufacturing processes. Consequently, it may be difficult to increase production in response to a sudden increase in demand [24]. The availability of biosimilars may help prevent shortages of biologics by increasing the number of suppliers, while potentially offering cost savings compared with reference products [24]. Tendering can lead to decreased competition in a particular market, which may lead to drug shortages if certain drugs then become more in demand [24]. The withdrawal of competitors from a market following the loss of a tender can also lead to long-term price rises due to the lack of competition [25]. Splitting tender awards allows for adequate competition and for the drug supply to be maintained, while avoiding dependence on a single supplier. However, this approach may reduce potential cost savings because economies of scale are usually smaller, and bidders may not always offer the lowest prices [24]. Despite these concerns, most European countries have adopted tendering to promote biosimilar adoption. In addition, most European countries have employed price regulations, physician incentives, and prescribing guidelines [26].

The following sections provide examples of successful rollouts of biosimilars that demonstrate benefits beyond savings. On the basis of the results of the literature search conducted for this review, the examples mostly come from Europe. While healthcare systems and demographics in high income countries might pose unique financial challenges for healthcare providers that make biosimilars particularly appealing, the reason for this publication bias is unclear. This may partially be due to the relatively lower number of biosimilars available in lower-income countries [27].

Adoption of Biosimilars in the UK

Following the launch of biosimilar filgrastim in the UK in 2008, existing guidelines on the use of granulocyte colony-stimulating factor (G-CSF) medicines were reassessed [22]. Guidance in several Strategic Health Authorities in England was updated to reflect the improved cost-effectiveness of biosimilar filgrastim versus alternative treatments and, as a result, G-CSF was moved to first-line cancer therapy. This led to an increased utilization of both reference and biosimilar filgrastim (104% increase between January 2009 and January 2014), representing a significant cohort of patients who may not have been able to access this treatment previously.

By expanding access to biologic therapies, biosimilars can significantly impact patient care and improve outcomes [28]. The National Institute of Health and Care Excellence (NICE) in the UK previously recommended that patients with RA receive biologic treatments only if they have severe disease [29]. Prior to the financial windfall created by biosimilars, NICE restricted funding of biologic treatments to a fraction of labeled indications owing to their prohibitive cost. For example, only patients with severe RA who failed several lines of conventional treatment could be reimbursed, delaying the most effective targeted biologic treatments until late in the course of disease and neglecting the label for moderate RA disease [30]. As the biosimilar price competition reduced the cost of treatment, the benefits of expanded patient care were realized in the updated 2021 NICE guidelines. The 2021 NICE guidelines recommend tumor necrosis factor (TNF) inhibitors as additional treatment options for people with moderate RA whose disease has not responded to conventional treatments [29]. Around 25,000 people in the UK with moderate RA now have access to biologic therapy [29], and can benefit from earlier treatment, which could affect their disease course and limit and even prevent irreversible joint damage [31].

Learning from their previous experience with biosimilar filgrastim, the National Health Service (NHS) in England also encouraged the collaboration of regional trusts and local commissioning groups, with benefit sharing included as an incentive for stakeholders. As part of this collaboration, targets were set for at least 90% of new patients to be prescribed the biologic medicine demonstrating the best value within 3 months of the launch of a biosimilar medicine, and at least 80% of existing patients within 12 months, or sooner if possible [32].

In the UK, biosimilar cost savings have been further used to expand treatment options and increase patient access to novel therapies. In 2018, NHS England reinvested savings into the Cancer Drugs Fund, a program created to reimburse timely access to promising innovative cancer medicines. The annual budget for the Cancer Drugs Fund (£320 million) is covered by the savings made from ten patent-expired medicines [33]. The Cancer Drugs Fund was designed for novel agents for which long-term evidence for cost-effectiveness is lacking [34]. This enabled the NHS to become one of the three fastest adopting healthcare systems for treatment innovation globally [35], with more than 80,000 patients so far benefiting from the scheme [36]. An example of how savings from patent-expired medicines can be reinvested was observed when the NHS became the first healthcare system in Europe to reimburse the chimeric antigen receptor T-cell therapy, tisagenlecleucel [37], for use in England and Wales for people with diffuse large B-cell lymphoma who have not responded to two or more previous treatments [38]. The drug has a list price of £282,000 for a single intravenous (IV) injection and is paid for using the Cancer Drugs Fund [39].

The use of biosimilars has created opportunities for the reinvestment of cost savings in services that benefit patients. In one hospital in Cardiff, UK, cost savings generated from switching from subcutaneous (SC) reference rituximab to IV rituximab biosimilars (estimated to be £300,000–£335,000 annually) were reinvested to establish off-site, nurse-led infusion clinics located closer to the homes of patients requiring chemotherapy for lymphoma [40]. These clinics offered reduced travel times and ease of parking for the administration of IV rituximab formulations compared with hospital visits. Feedback from patients was overwhelmingly positive. The benefits seen for these patients can also be expanded to other patients who require IV therapies, such as those with inflammatory diseases.

A program, funded by a gain-share agreement between University Hospital Southampton NHS Foundation Trust and local commissioning groups, managed the switch from reference infliximab to biosimilar infliximab CT-P13 in patients with inflammatory bowel disease (IBD) at a teaching hospital in Sheffield, UK. This program delivered significant cost savings and investment in clinical services, while maintaining similar treatment outcomes [41]. A patient panel played a significant role in developing this program, guiding development of the content of a patient information sheet and advocating for specific reinvestment of cost savings. Switching resulted in a rapid reduction in drug acquisition costs of £40,000–£60,000 per month billed to the care commissioning group, despite a continuing increase in the number of dispensed vials. These cost savings were used to hire extra healthcare staff and improve healthcare resource allocation, leading to a better service and quality of patient care. Patients reported a similar incidence of adverse events before and after the switch to CT-P13, with no clinically significant changes in mean C-reactive protein, albumin, hemoglobin levels, or platelet and white cell counts post-switch. The mean IBD-control-8 patient-reported outcome (PRO) score improved from 11.2 at the time of the switch to 14.0 after the third dose (p = 0.041). There were no significant differences in drug persistence between reference and biosimilar infliximab (p = 0.94), and no increase in immunogenicity after the switch [41].

Benefit-share agreements have been implemented where part of the savings derived from the use of biosimilars is shared and reinvested directly back to the hospital department involved. Such agreements have been successful in increasing biosimilar use and may enable hospitals to improve healthcare services. This could include expanding healthcare teams, improving infrastructure, or providing better training for non-specialist healthcare professionals (HCPs) [23, 40, 42]. In the UK, the Royal Free London Foundation Trust was able to recruit more IBD nurses from their share agreement, which generated savings of £2.5 million [43]. These nurses provide support for patients during clinic visits and remote help with problems or questions, and have improved organization of the care pathway [42]. A benefit-share agreement at the York Teaching Hospital Foundation Trust has enabled them to employ an IBD specialist nurse at a new location, following a switch from reference infliximab to a biosimilar, and thereby also reducing the distance patients need to travel [43].

Adoption of Biosimilars in the Rest of Europe

In Norway, increased competition following the introduction of biosimilars has resulted in a trend toward earlier treatment initiation with biologic disease-modifying anti-rheumatic drugs (DMARDs) across all inflammatory joint diseases, and at a lower level of disease activity [5, 44]. For example, the introduction of financial incentives to switch patients from reference to biosimilar medicines resulted in an 80% market share for epoetin and filgrastim biosimilars, and even higher market shares for TNF inhibitor biosimilars. Patients with RA now typically have low-to-moderate disease activity at the time of starting biologic DMARD treatment, rather than moderate-to-high disease activity [5].

A decrease in time to biologic DMARD initiation was also seen in Germany following the introduction of biosimilars, together with an increase in biologic DMARD use. An analysis of claims data from the Bavarian Association of Statutory Health Insurance Physicians for the period 2014–2019 was conducted, during which time three biosimilars entered the market [45]. During the observation period, the proportion of diagnosed patients receiving therapy increased from 38.5% to 43.2%. The median duration of treatment before first-time biologic DMARD initiation decreased from 3.2 years in 2014 to 2.2 years in 2019, while prescriptions for targeted therapies increased from 12.3% to 20.4% over the same period [45].

In Sweden, prior to the availability of biosimilars, the clinical opinion of three physicians was required before filgrastim initiation. The introduction of filgrastim biosimilars and the associated reduction in costs for G-CSF treatment of febrile neutropenia prompted regional authorities to relax restrictions on prescribing, meaning that the opinion of only one physician was required [46]. Giving physicians autonomy to prescribe was associated with a fivefold increase in G-CSF uptake in the Swedish Southern Healthcare Region, leading to greater access to these drugs and improved patient outcomes [46].

National tender systems are effective ways to create competition between manufacturers of reference medicines and biosimilars, even in countries where different regions have their own budgets for pharmaceuticals [16]. Norway has a national tender and procurement system for biologics and other costly drugs, financed by hospitals [47]. Each manufacturer offers a product price for 12 or 24 months [48]. This process makes it easy for lower-priced biosimilars to enter the healthcare system rapidly and become the recommended drug for all approved indications [16]. Biosimilar infliximab was launched in Norway in December 2013, priced 33–39% lower than the reference product [48]. By 2015, the price of the biosimilar infliximab was reduced to 51–69%, less than that of the reference product. Biosimilar infliximab then became the preferred biologic DMARD for all reference product indications when initiating a biologic DMARD or when switching to a TNF inhibitor in naïve patients [48].

Competition from biosimilars has led to an increased uptake of biologics in Norway and Denmark. In Norway, access to infliximab increased by approximately 80% between 2015 and 2021. Despite this increased uptake, the total cost of biologics has decreased by approximately US$80 million over the same period [5]. For example, overall, the use of TNF inhibitors in Norway has increased 300–400% since the introduction of biosimilars; however, the competitive procurement and tender system has contributed to a considerable total cost reduction [47]. In Denmark, following patent expiration of reference adalimumab in October 2018, the proportion of biosimilar use rapidly increased from 71.6% in November 2018 to 95.1% in December 2018. In parallel, the costs of adalimumab decreased by 82.8% from September 2018 to December 2018, despite the number of injector pens increasing by 15% [49]. Data from Denmark and Norway illustrate that the uptake of biosimilars has been particularly successful for TNF inhibitors [47]. Similar success may be observed in the future for other types of biosimilars.

In Belgium, after a tender for infliximab at AZ Delta Hospital, a mandatory switch from reference product to biosimilar medicine was implemented by a nurse-led interdisciplinary team for all patients with IBD [42]. Patients and HCPs were informed about the switch and a pocket dictionary was developed for nurses that included frequently asked questions. The resulting cost savings were reinvested, allowing the hospital to increase from one part-time to one full-time IBD nurse to support patients during clinic visits and provide help with problems or questions at home [42]. Other benefits for patients included expanded access, a simplified administration protocol, shorter waiting times, and improved care pathways.

Adoption of Biosimilars Beyond Europe

In Australia, the first filgrastim biosimilar was approved by the Therapeutic Goods Administration in 2010 and listed on the Pharmaceutical Benefits Scheme (PBS) in 2011 [50, 51]. This was followed by the listing of a second filgrastim biosimilar in 2013 [51]. The cost of filgrastim has reduced by nearly 80% since 2010, with cost savings reinvested into the PBS, thereby ensuring that patients have the earliest possible access to new medicines [51, 52].

In New Zealand, significant cost reductions driven by biosimilars led to the increased use of G-CSF, enabling more patients to benefit from treatment and improving health outcomes [53]. In late 2012, biosimilar filgrastim was the first biosimilar drug to be funded in New Zealand and at a lower price than the reference product. This resulted in annual cost savings of NZ$5 million and enabled wider funded access to the drug. The introduction of biosimilar filgrastim also significantly reduced the total costs of the G-CSF market, with a corresponding expansion in G-CSF use of almost 25% by 2014. Increased G-CSF use led to significantly improved clinical outcomes in patients with cancer, most notably a reduction in the incidence of neutropenic fever from approximately 30% to less than 7% in women receiving docetaxel-based chemotherapy [53].

In Canada, an initiative was launched to expand the use of biosimilar medicines under its public drug programs [54]. Between May 2019 and October 2022, seven jurisdictions implemented a mandated switching policy, whereby patients using a biologic to treat a chronic condition were transitioned to a biosimilar under the supervision of their treating physician. Savings from the use of biosimilars were reinvested to support patient access to public drug coverage and new drug benefits [54]. During the 6-month transition period following implementation of the switching policy in one Canadian province (British Columbia), prescriptions for biosimilars among all etanercept prescription refills covered by PharmaCare achieved almost full penetration in the market, rising from 17.3% (349 of 2016 prescriptions) in May 2019 to 96.9% (1887 of 1948 prescriptions) in December 2019 [55]. Over 1 year of post-switch follow-up, visits to rheumatologists and other specialties increased, but no permanent unintended changes in health services utilization, such as hospital admissions and emergency department visits, were observed. Patients also had fewer days on conventional synthetic DMARDs, oral steroids, and non-steroidal anti-inflammatory drugs than before the switch [55]. Savings from biosimilars enabled patients with ulcerative colitis in five provinces access to infliximab (Remicade^®). Previously, Remicade^® was not available for these patients owing to its high cost [56]. British Columbia has reallocated savings from biosimilars to reimburse additional medicines, diagnostic tests, and additional nursing support for patients with RA and IBD. From 2019 to 2024, British Columbia saved CA$732 million following a program of mandatory switching, with 87% of patients being prescribed biosimilars by 2024 [57]. Canada has thus seen improved access to accepted diagnostic tests that were not previously covered by provincial healthcare plans for budgetary reasons.

A cross-sectional study compared biosimilar uptake at a US Veterans’ Affairs Medical Center (VAMC) with that of an academic medical center, with differing institutional incentives for infused medications [58]. The uptake of biosimilars, particularly infliximab, was faster at the VAMC than at the academic medical center, since the preferred use of the biosimilar resulted in financial savings for the VAMC [58]. Biosimilar infliximab was used in 38% of infusions at the VAMC, with an 81% lower cost per vial compared with reference infliximab [58]. At the academic medical center, reference infliximab was used in 99% of patients [58]. These findings, and differences between rates of uptake of biosimilars in the USA compared with Europe, are discussed in another editorial [59].

Private healthcare systems in the USA have also implemented programs to transition from reference biologics to biosimilars. Kaiser Permanente Colorado, an integrated healthcare provider and insurer, reported adoption rates of at least 90% for biosimilar filgrastim, trastuzumab, bevacizumab, rituximab, and infliximab in 2022 [60]. Providence St Joseph Health, a large US nonprofit health system, reported savings of US$26.9 million in 2 years following the creation of a biosimilar utilization management program, which used biologic-utilization monitoring and financial performance analysis to drive biosimilar adoption [61]. Aside from driving biosimilar uptake and creating savings, these initiatives can create efficiencies within healthcare systems through simplified workflows for providers prescribing biologics and improved record keeping [61].

In Brazil, no biologic drugs were recommended by the Ministério da Saúde for psoriasis before 2019, despite the approval of TNF inhibitors for this indication. In 2019, three adalimumab biosimilars were approved, generating competition on pricing [62]. In 2020, adalimumab or etanercept were recommended after failure of standard systemic therapy, while ustekinumab or secukinumab were recommended after failure of adalimumab or etanercept [63]. Between 2020 and 2023, an annual volume growth rate of 6.3% was observed for adalimumab biosimilars, potentially indicating increased access to this drug [64].

Complicating the picture outside of high-income countries is the presence of non-innovator biologics that have not undergone review according to a regulatory pathway for biosimilars, but are nonetheless marketed in several countries, referred to as biomimics, biocopies, or intended copies. While the similarity and safety of biomimics has been questioned [65], the available literature on these molecules remains limited, and their effect on competition with reference biologics and on the commercial viability of biosimilars is unclear. While biomimics are likely to increase price competition in markets where they are available, they may also make those markets less attractive to manufacturers of biosimilars if regulators, HCPs, and patients do not distinguish between biomimics and biosimilars.

What Holds Back Biosimilar Adoption

Limitations in biosimilar availability are a significant barrier to biosimilar adoption. In an analysis of biosimilars used in RA across 18 countries from 2015 to 2022, the number of biosimilars available for each reference biologic varied widely, with fewer or no biosimilars available in lower-income countries relative to European countries and Canada. Biosimilar uptake was also much lower in lower-income countries, in line with biosimilar availability [27].

In the next few years, biosimilar availability may become a concern globally due to a lack of biosimilars in development. As of November 2024, among biologics that are expected to lose exclusivity in Europe by 2030, the 8 molecules with sales of more than €1 billion all have proposed biosimilars in development, while 5 out of 8 molecules (38%) with sales of €1 billion to €500 million and 46 out of 53 molecules (87%) with sales of less than €500 million lack publicly reported pipeline activity. This “biosimilar void” translates to a lack of biosimilars for biologics with ~€6 billion in yearly sales [6].

Where biosimilars have been available, policy measures in other healthcare systems targeting the price and uptake of biosimilar medicines have demonstrated substantial cost savings, thereby providing opportunities to support treatment sustainability [54, 55, 66]. For example, in the UK, France, and Germany, switching patients from infliximab to biosimilar CT-P13 for RA was estimated to save between €233 and €433 million over 5 years [5]. However, the adoption of biosimilars has not been consistent across Europe. In the UK, NHS England encouraged benefit sharing to promote biosimilar uptake [32]. Despite positive examples noted earlier, some benefit sharing programs encountered challenges. Although the lack of reporting on the outcomes of some programs made assessments of success difficult, in some cases, potential beneficiaries lacked clear pathways for claiming savings, and negotiations over the splitting of any savings could be drawn out [67]. In instances where benefit-sharing programs were based on price differences between reference biologics and biosimilars, these schemes became ineffective when price competition drove down the price of the reference biologic. Other such benefit-sharing programs were redesigned on the basis of fixed prices [67].

The introduction of anti-TNF biosimilars in Italy, Portugal, and Spain resulted in large differences in adoption rates between regions within those countries. These differences were found to be driven by national and regional factors. In contrast with other European countries, health authorities in Italy, Portugal, and Spain were vague regarding the substitution of reference biologics and biosimilars. In addition, policy frameworks and procurement practices did not consistently support switching [68]. The lack of incentives for healthcare providers has also been noted as a barrier to biosimilar uptake in Spain, caused by the lack of legal and institutional structures [69]. Healthcare resources were also not consistently made available for switching, notably in Portugal, where uneven distribution of healthcare spending has resulted in disparities in the availability of healthcare facilities and staff [68]. Biosimilar uptake in Portugal may also be hindered by a 2010 ordinance, obliging public hospitals to provide biologics prescribed at private facilities for rheumatic diseases free of charge, without the ability to modify the prescription [70].

Discussion

The case studies presented here demonstrate the substantial value of biosimilars in real-world settings (Fig. 1). In healthcare systems already making extensive use of biologics, the introduction of biosimilars has led to substantial cost savings as another measure to mitigate medical expenditures and the financial burden of reference biologics. Biosimilars are potentially key components of any sustainable healthcare system and may impact care by providing both direct and indirect benefits for patients. Increased uptake of biosimilars can also help reduce the financial burden on healthcare systems by promoting earlier, timelier, and longer access to therapies for more patients, and helping to free up funds for the use of innovative therapies. Earlier and more timely treatment with biosimilars can also potentially help to reduce the overall disease burden and associated costs, for example, by reducing possible long-term complications, and offering more choices during the window of opportunity and for second- and third-line treatment options.

Fig. 1.

Clinical and patient benefits of biosimilars in real-world settings

All patients who are stable with their existing treatment can expect similar clinical outcomes from biosimilar treatment. Cost savings realized from using biosimilars then benefit healthcare systems and other patients with no loss of efficacy, as shown by the results of the NOR-SWITCH study, where switching from reference infliximab to CT-P13 was not inferior to continued treatment with reference infliximab [71]. For patients in whom there is no response or who experience loss of efficacy (to either the reference product or biosimilar), drugs with other MoAs or newly approved innovative medicines could be considered, given the cost savings from using biosimilars for first-line biologic treatment.

A systematic review and network meta-analysis of 17 randomized trials involving 6562 patients found that switching from a TNF inhibitor reference product to a biosimilar did not significantly impact effectiveness, safety, or immunogenicity [72]. The risks of treatment-emergent adverse events, discontinuation, and anti-drug antibodies were comparable between patients who switched and those who remained on the reference product [72]. An analysis of data from the DANBIO registry found no major safety signals in patients who switched from reference etanercept to biosimilar etanercept [73], results also seen with other TNF inhibitors. Other real-world data have shown that patients who switched from TNF inhibitor reference products to their biosimilars had comparable treatment duration with patients who remained on the reference products [74]. Evidence has shown no negative impact on patients of switching back from a biosimilar to a reference product [75]. In a meta-analysis of data from 5252 patients in randomized controlled studies and extension studies, which included a switch treatment period to or from a biosimilar and its reference biologic, a similar incidence of anti-drug antibodies and neutralizing antibodies were reported in patients who were switched versus those who were not switched. The rates of deaths, serious adverse events (including immune-related adverse events, i.e., anaphylaxis, hypersensitivity reactions, and injection-site reactions), and discontinuations were also similar between switched and non-switched patients [76]. Analysis of post-approval cumulative patient exposure and safety data for eight Sandoz biosimilars, covering 1.3 billion patient treatment days for adalimumab, epoetin alfa, etanercept, filgrastim, infliximab, pegfilgrastim, and somatropin, and 1.8 million patient doses for rituximab, also found that the overall benefit–risk profile of each biosimilar was favorable and consistent with the respective reference biologics [77].

Given the current emphasis on Europe in the identified literature, further research on the adoption of biosimilars is required in countries where knowledge is more limited. The adoption of biosimilars depends on their acceptance by HCPs, patients, and payers, which is often suboptimal [5, 15]. Lack of patient acceptance and negative attitudes towards biosimilars can be related to inadequate knowledge and understanding, and may contribute to nocebo effects and potential treatment failure [15]. Moreover, misinformation and disparaging statements on biosimilars have impacted patient acceptance [78]. The provision of easy-to-understand, evidence-based information tailored to individual patients’ needs, as well as open, positive communication about the benefits of biosimilars, are important, particularly before transitioning from a reference product to a biosimilar [15]. Patient advocacy groups can provide support by providing biosimilar education, sharing patient stories, and providing resources to aid patients in discussions about biosimilars with their HCPs [15]. Patient advocacy groups can also coordinate with HCPs to counter misinformation on biosimilars [78].

Although biosimilar uptake has increased in many countries, concerns have been raised regarding their long-term sustainability [79], which is essential for a competitive market and to drive continuing innovation. Vulto et al. (2020) proposed the definition of a sustainable biosimilar market as an environment where, “all stakeholders, including patients, benefit from appropriate and reliable access to biologic therapies. Competition leads to a long-term predictable price level, without compromising quality, while delivering savings that may be reinvested” [80]. Key drivers of biosimilar market sustainability include selective purchasing, pricing, and reimbursement strategies; safeguarding the interests of patients; maintaining physician autonomy and patient choice; good pharmacovigilance practices; and appropriate levels of competition to ensure a consistent supply of high-quality products [80]. It is also important for pricing and reimbursement policies to ensure a market environment where biosimilar manufacturers retain a persistent incentive to remain in the market [80]. Long-term sustainability can be achieved through: (1) the acceptance of biosimilars as a key part of “healthy” healthcare systems, which may require an improved understanding of their potential and impact among different stakeholders; and (2) shared decision-making between patients and HCPs within a real-world context of affordability and improved patient outcomes. If biosimilars are not widely accepted, we believe that healthcare costs could increase, meaning fewer patients will be able to receive treatments, potentially resulting in increased morbidity and mortality.

Many new biologic medicines are in development and the regulatory environment for biosimilars continues to evolve [81], presenting a growing number of opportunities for biosimilars. In 2004, the EMA pioneered the regulation of biosimilars by establishing a robust regulatory framework, and guidance has continued to evolve over time [82]. In recent years, European medical societies and other expert groups have increasingly endorsed biosimilar use in their position statements [83–85]. However, the regulatory environment for biosimilars remains complicated in some countries, such as the USA. The FDA previously recommended that a multiple-switch study be performed to obtain the designation of “interchangeable biologic” for a given biosimilar [86]. Comparative efficacy studies are routinely performed for the EMA and FDA to confirm biosimilarity, particularly if no pharmacodynamic markers exist. A retrospective review of approved biosimilars in the European Union and the USA has shown that, as of 2020, biosimilar efficacy was confirmed in 100% of comparative efficacy studies and for 95% of these, the comparative efficacy studies added no value to the scientific review process during biosimilar approval [87]. Considering such evidence, in 2024, the FDA proposed a revision to its guidance on interchangeable biologics, indicating that multiple-switch studies should no longer be routinely required for biosimilars to obtain an interchangeability designation [88]. Furthermore, the Biosimilar Red Tape Elimination Act, initially proposed to the US Senate in 2023 and yet to proceed through the legislative process, proposes that all biosimilars should be deemed as “interchangeable” upon approval, with no requirement for switching studies unless there is an explicit reason to think such a study is necessary [89].

Finally, the availability of new biosimilars for use in immunology and oncology has expanded the number of sustainable treatment options and presents additional opportunities to improve patient care [90]. A timely example is the patent protection expiration of ustekinumab (July 2024) [91]. It is likely that the impact of ustekinumab biosimilars on medicine budgets and patient access may be large, given that reimbursement for the reference biologic has been restricted to a few of the labeled indications owing to its high cost [92, 93]. To ensure that the benefits of both new and existing biosimilars are fully realized, strategies shown to be successful should be adapted across healthcare systems worldwide [5]. Maximizing the value of biosimilars will require cooperation among multiple stakeholders [14]. Any disparities between treatment guidelines and national reimbursement criteria should be addressed to enable biosimilars to be accessible to patients as quickly as possible [14].

Conclusions

In real-world settings, biosimilars deliver value beyond cost savings and provide a range of clinical and patient benefits. Greater use of biosimilars is an achievable goal; however, healthcare systems must drive increased uptake and ensure that their value is understood by all stakeholders. Furthermore, healthcare authorities need to put in place schemes that maximize the benefits of greater biologic competition and ensure that these schemes are transparent and flexible enough to encourage and maintain competitive pricing for biosimilars. Professional societies and national health ministries also need to provide clear guidance on how biosimilars fit into the treatment landscape. There is the potential for cost savings from biosimilars to be passed on to patients in some countries, which would require clear mechanisms for transferring these savings. It is also hoped that biosimilars will increase access to biologics in historically underserved communities.

Funding

Open access funding provided by Diakonhjemmet Hospital.

Declarations

Conflicts of Interest

T.K.K. reports fees for speaking and/or consulting from AbbVie, Amgen, Celltrion, Egis, Ewopharma, Gilead, Hikma, Janssen, Mylan, Novartis, Oktal, Pfizer, Sandoz, and UCB; and research funding from AbbVie, BMS, Galapagos, MSD, Novartis, Pfizer, and UCB. N.B. declares consultancy fees received from EULAR, Galapagos, Grunenthal, and Sanofi. I.B., W.B., and G.B. are employees of Sandoz. S.D. declares consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Enthera, Ferring Pharmaceuticals, Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, TiGenix, UCB, and Vifor; and speaker fees from AbbVie, Amgen, Dr Falk Pharma, Ferring Pharmaceuticals, Gilead, Janssen, Mylan, Pfizer, and Takeda. J.G. declares speaker fees from AstraZeneca, Celltrion, Chiesi, Sandoz, and Sanofi. Z.M. has no conflicts of interest to declare. C.T. declares consultancy fees received from Biogen, Nordic, Pfizer, and Sandoz; advisory board fees from AbbVie, Nordic, Pfizer, Roche, and Sandoz; and research grants from Jamp and Pfizer. L.W. declares advisory fees received from Act4Biosimilars and PAN Therapeutics. P.C. declares speaker fees from Celltrion, Viatris (formerly Mylan), Pfizer, Novartis, and Sandoz.

Funding

This study was funded by Sandoz Group AG. The funder had a role in the study design, data collection, data analysis, and manuscript preparation. The open access fee was also sponsored by Sandoz Group AG.

Ethics Approval

Not applicable.

Patient Consent to Participate/Publish

Not applicable.

Availability of Data and Material

Data available on request.

Code Availability

Not applicable.

Author Contributions

I.B., W.B., and G.B. contributed to the study design, literature search, and data analysis. N.B., Z.M., C.T., and L.W. contributed to the study design, data analysis, and manuscript development. T.K.K., J.G., and P.C. contributed to the study design and manuscript development. All authors were involved in the preparation and review of the manuscript. All authors read and approved the final manuscript.