Fostering healthcare system sustainability through efficient practices: Can adopting biosimilars ease the financial burden of rheumatoid arthritis?

1. Introduction

Rheumatoid Arthritis (RA) is an autoimmune condition characterized by persistent inflammation of the synovial joints, which can cause joint degeneration, functional disability and systemic complications. About 0.5-1% of people worldwide, most of whom are women, are affected by the disease, which frequently leads to severe disability and an increased need for healthcare resources. RA treatment has changed dramatically with the introduction of biologic treatments, which provide notable gains in disease control.¹ Hence, the high cost of biologic treatments, especially over an extended period of time, places a significant financial strain on healthcare systems around the world.²

Biosimilars, i.e. biologically similar medicines, have become more and more affordable substitutes for original biologics (originators) when the patents of the latter expire.³ A biosimilar product shares many quality, safety and efficacy characteristics with an approved reference product. It is anticipated that the introduction of biosimilars will lower drug costs, broaden access to biologic treatments and enhance the sustainability of healthcare systems.⁴ This paper investigates the economic impact of use of biosimilars by RA patients, with an emphasis on the sustainability of healthcare systems.

2. Biologic treatments in RA

Biologic disease-modifying antirheumatic medications (bDMARDs) have become a mainstay in the treatment of moderate to severe RA, especially for patients who do not respond well to conventional synthetic DMARDs (csDMARDs).¹ These biologics, including indicatively interleukin-6 (IL-6) inhibitors (like tocilizumab) and tumor necrosis factor (TNF) inhibitors (like infliximab, etanercept and adalimumab), among others, have shown impressive success in reducing disease activity and improving patients’ quality of life.¹

However, healthcare systems encounter a substantial financial burden due to the high cost of bDMARDs, especially in settings with limited resources. The fact that RA is a chronic disease that requires permanent or extended treatment intensifies this financial burden even more. As a result, the need for and cost of biologic medicines are on the rise, posing a risk for the sustainability of healthcare systems.

3. Inequities in access to biologics

TNF inhibitor availability has enhanced RA patients’ quality of life and lessened the disease burden for society as a whole.⁵ A number of studies have demonstrated that RA is more severe in poorer countries and that treatment access disparities may contribute to this finding. In addition to demonstrating a negative association between gross domestic product (GDP) and the average disease activity score (DAS28), the QUEST-RA study found that, in low-GDP countries, biologically treated RA patients had a significantly lower DAS28 than non-biologically treated patients.⁶ This finding suggests that not all patients in low-GDP countries receive the necessary biologic treatment. Furthermore, data from the COMORA study demonstrated that the association between disease activity and socioeconomic position is evident both at individual and country level (measured as GDP).⁷

According to Putrik et al.,^8,9 there are serious disparities in RA patients’ access to biologic treatments. Out of 46 European countries, 22% did not have any reimbursement for biologics available, whereas 59% presented annual treatment costs that exceeded the GDP per capita, up to a maximum of 11 times. The country’s socioeconomic status and RA health indicators were positively correlated with the number of approved and reimbursed biologics⁸ and a more lenient prescribing policy.⁹ Again closely related to GDP, accessibility was determined by availability, affordability and acceptability, which differed across countries.^8,9 Another study in a real-world setting revealed that bDMARDs use in RA patients varied considerably across six central and eastern European countries.¹⁰

4. The emergence of biosimilars in RA

Biosimilars are biologic medicines that, in terms of structure, mode of action and clinical efficacy, are very similar to their already approved originator biologics. Although biosimilars are not identical to originator biologics due to the fact that biologic manufacturing processes are complicated, the development of biosimilars must adhere to strict regulatory requirements that guarantee their quality, safety and efficacy.

With biosimilars entering the RA treatment armory, there is a big opportunity to cut healthcare expenses without sacrificing therapeutic outcomes. Biosimilars provide significant cost savings potential since they typically enter the market between 20 and 40 percent less expensive than their originator biologics. As the patents on some well-known biologics, including adalimumab, etanercept and infliximab, have expired, a number of biosimilars have been already approved and introduced into certain international markets ( Table 1).

5. Economic implications of biosimilars adoption in RA

The emergence of biosimilars has provided a less costly option to biologics. The use of biosimilars in RA treatment poses an economic impact that may be examined from different point of view, including medication costs, the utilization of healthcare resources, patient outcomes and wider implications for the sustainability of healthcare systems.

6. Challenges and barriers to biosimilar adoption

Even though biosimilars come with quite obvious economic benefits, a number of challenges and barriers prevent their widespread adoption and the turn of all their potential into value. Various reasons may account for low uptake of biosimilars, including regulatory, clinical and market-related barriers, the attitudes of physicians and patients to the use of these drugs and the reimbursement conditions in different countries.

7. Economic evaluation of biosimilars in RA

Economic evaluation studies confirm cost savings from the uptake of biosimilars in RA. In Poland, Stajszczyk et al.³⁵ used 12,687 infliximab, etanercept and adalimumab treatment courses to perform a retrospective budget impact analysis. Out of the estimated €243 million in overall savings for TNF inhibitors, €166 million were attributable to reduced treatment costs for rheumatoid and musculoskeletal diseases (RMDs) from the public payer perspective during an eight-year period. Real-world savings of €133 million and €107 million were estimated, respectively. Of the entire savings, the rheumatology sector generated between 68% and 92%. Overall, the mean annual cost of treatment dropped by 75% to 89%. Approximately 45,000 patients with RMDs may potentially be treated if all budget savings were used towards the reimbursement of extra TNF inhibitors.

In order to evaluate the budget impact of infliximab biosimilar CT-P13 in RA treatment during a three-year period in six Eastern European countries (Bulgaria, Czech Republic, Hungary, Poland, Romania and Slovakia), Brodszky et al.³⁶ built a model which considered only the direct drug costs in two scenarios. In the first scenario, 65% of patients started a new biologic therapy with CT-P13, and in the second, 80% switched from the originator to CT-P13. Taking into account a 25% discount over the originator price, estimated savings in the first scenario were €15.3 million, while savings in the second scenario were €20.8 million. In this model, 1,205 and 1,790 additional RA patients would receive therapy in the first and second scenarios, respectively, if budget savings were spent in the reimbursement of additional infliximab treatments.

A comparable budget impact model was created by Jha et al.³⁷ to assess CT-P13 in six immune-mediated diseases over a one-year period in five European countries: Germany, the UK, Italy, the Netherlands and Belgium. Based on a 25% switch rate and a 50% biosimilar uptake in newly-treated patients, the expected savings in RA for the 10%, 20% and 30% discount scenarios were €2.3, €4.6 and €6.9 million, respectively. According to this estimate, treating an extra 300, 676 and 1,158 RA patients would arise from the 10%, 20% and 30% discount scenarios, respectively.

In a real-world setting in France, Beck et al.³⁸ aimed at evaluating the potential cost savings after a year of using biosimilar infliximab to treat RA patients. Compared to adalimumab or etanercept, the cost of managing RA patients with biosimilar infliximab was significantly lower (€11,907 vs. €12,981 and €13,551 respectively). If every adult RA patient receiving treatment with infliximab changed to the biosimilar drug, the estimated annual cost savings would reach €13.6 million on a nationwide level. If all these savings were reallocated for the treatment of RA, 1,141 more patients could be treated.

The launch of infliximab and etanercept biosimilars resulted in savings of £38.8 million over a two-year period, according to an analysis of rheumatology specialties in the UK.³⁹ This was attributed to both the uptake of biosimilars and price reductions for originator products. Similarly, the availability of biosimilars in Scandinavian countries has heralded significant cost savings and increased patient access to biologics, despite already substantial use.⁴⁰

According to data from the Danish national DANBIO registry,⁴¹ the etanercept biosimilar SB4 accounted for 84.2% of all etanercept use within a year of the originator etanercept patent expiration. When the first infliximab biosimilar was introduced in Denmark in 2015, a similar pattern was seen with infliximab biosimilars, with costs roughly reducing by two thirds when moving from originator to biosimilar infliximab.⁴¹ According to another Danish study, after their market introduction, adalimumab biosimilars quickly replaced the originator drug. Overall, 95.1% of adalimumab prescriptions involved a biosimilar and thus, the cost of adalimumab treatments dropped by 82.8%.⁴²

Using hospital data from 2014 to 2018 in the Netherlands, Müskens et al.⁴³ examined how the introduction of biosimilars affected medication expenditure in RA patients and which patients acquired access to biologics due to the availability of biosimilars. They came to the conclusion that there was a consistent downward trend in the average cost per patient receiving a biologic treatment following the launch of biosimilars. However, as more patients began receiving biologic treatments, the budgetary relief brought about by the introduction of biosimilars to the market swiftly evaporated.

Valido et al.⁴⁴ examined efficacy, safety and cost savings of switching adult RA patients receiving originator infliximab for at least six months and with stable disease activity to biosimilar infliximab (CT-P13) in Portugal. Over a median follow-up duration of 15 months, disease activity remained steady and was comparable to the values noted with originator infliximab. The switch from originator infliximab to a biosimilar resulted in a 26.4% reduction in expenditure without compromising efficacy or safety. Switching RA patients from infliximab to the biosimilar CT-P13 in the UK, France and Germany would save €233 to €433 million over the course of five years (representing discounts of 20% and 30%, respectively). Over 7,500 more RA patients could receive biosimilar treatment thanks to the savings from the 30% discount.¹⁶

For patients with established RA who do not respond to methotrexate, Patel et al.⁴⁵ compared two early intervention pathways (either adding originator biologic TNF inhibitors or adding biosimilar TNF inhibitors to methotrexate monotherapy at 6 months) with a standard intervention pathway (adding originator biologic TNF inhibitors to methotrexate monotherapy at 12 months). Comparing early intervention with an originator biologic TNF inhibitor at 6 months to standard intervention at 12 months, the early intervention group experienced increases in utilities of 0.10 quality-adjusted life-years (QALYs) per patient and total lifetime expenses of £1,692. An incremental cost-effectiveness ratio (ICER) of £17,335/QALY was obtained as a result. An early intervention with a biosimilar TNF inhibitor resulted in an ICER of £713/QALY, with costs rising by £70 and utilities by 0.10 QALYs per patient.

8. Discussion

Use of biosimilars can maximise benefits for RA patients by enhancing equity of access to biologics and providing affordable treatment for early disease control. Twelve strategies for the cost-effective use of bDMARDs were established through individual and group discussions by an international task force made up of thirteen specialists from seven European countries in the fields of pharmacology, epidemiology and rheumatology.⁴⁶ A Delphi procedure was used to develop a set of five overarching principles and twenty points to take into consideration for each strategy based on evidence from relevant systematic reviews and randomized controlled trials. Experts agreed that since approved biosimilars and originators are viewed similarly, all guidelines apply equally to both. Additionally, consensus was achieved that where a biosimilar is the most cost-effective version of the medication, it should be chosen if approved by a drug authority in a highly regulated area and that switching from an originator to one of its biosimilars should be taken into consideration if it lowers the overall cost of treatment.⁴⁶

The use of biosimilars in RA patients has drawn criticism in terms of economic implications. Evidence for the cost savings associated with biosimilars adoption in RA originates mostly from budget impact models. Nevertheless, this type of economic evaluation assesses the economic impact, does not target a beneficial investment, does not take into account health outcomes, considers the payer’s prospects, only looks at direct costs, has a short-term horizon and measures the total expenditure. Furthermore, because many of the variables (such as the official and real acquisition cost of biosimilar and originator drug, price discounts, the market share of biosimilars among newly treated and switching RA patients, treatment discontinuation or switching to other biologics, among others) are based on assumptions that may vary between regions, it is also challenging to predict the accuracy of budget impact models and the true extent of economic gains.

A central issue of the criticism pertaining to the economic implications of biosimilars use in RA is the originator-to-biosimilar non-medical switch (NMS) policies. NMS refers to changing a stable patient’s medication for reasons unrelated to medical necessity (usually driven by factors like cost, insurance coverage, or formulary changes, rather than the medication’s efficacy or safety). Real-world originator-to-biosimilar NMS studies have revealed a discontinuation rate for infliximab from 14.7% to 81.5%⁴⁷ and for etanercept from 7% to 17%⁴⁸ due to adverse events or loss of efficacy. A retrospective cohort analysis using the administrative databases of three local health units in Italy showed that the treatment costs for RA patients who switched their initial biologic medication during the first year of follow-up were higher than those who did not.⁴⁹ Gibofsky et al.⁵⁰ assessed the short-term costs of switching stable patients with autoimmune diseases from originator biologics to biosimilars in rheumatology from the perspective of US providers and third-party payers. For N=3,609 patients with an NMS rate of 16.6%, the total switching costs for payers were $771,460, primarily because of follow-up visits and extra laboratory testing. The primary cost driver in the sensitivity analyses was the NMS rate. The overall switching costs for payers increased to $1.19 and $2.39 million, when the NMS rate was raised to 25% and 50%, respectively.⁵⁰

The cost of NMS in a stable RA population (patients responding to originator etanercept with no treatment changes within the preceding 6 months) in the UK was estimated by Tarallo et al.⁵¹ A survey of 150 rheumatologists from five EU countries (France, Germany, Italy, Spain, UK) provided data on the percentage of patients who switch therapies, baseline healthcare resource use and the effect of switching on resource use. According to this model, 1,259 (25.2%) of the 5,000 patients receiving originator etanercept would switch to a biosimilar. Following a three-month period, 26.3% of patients switched once more; 8.3% went back to the originator, 3.8% to a different biosimilar and 14.2% to a different biologic. In all impact scenarios, the switch was more expensive than continuing the originator’s treatment, even if originator etanercept cost more than biosimilars. Annual costs per patient were higher when switching treatments than when staying on the originator treatment. Switching was associated with higher utilization of healthcare resources.⁵¹

In the short term, any additional resources needed to support the switch from an originator product to a biosimilar - such as extra outpatient appointments – may potentially offset the biosimilar’s cost savings. Although data from the DANBIO registry showed no evidence of an increase in outpatient visits following a switch from originator infliximab to a biosimilar,^52–54 Moorkens et al.⁵⁵ found that in some Swedish counties, the extra effort required to actively swift patients from the originator product did not outweigh the slight cost reduction provided by biosimilar etanercept.

Whether or not the use of NMS in patients with stable RA results in higher costs -measured not only on adverse events and loss of efficacy, but also on hospitalization costs, missed workdays, absenteeism and worsening QALY with an increase in ICER over time – will be confirmed by real-world data and cost-effectiveness analyses. Future cost-effectiveness evaluations must, therefore, make every effort to be as precise as possible, to include the most relevant data and be updated on a regular basis.

9. Conclusions

The adoption of biosimilars among RA patients has a major economic impact and important consequences for the sustainability of healthcare systems. Biosimilars represent a viable substitute for expensive biologics, allowing healthcare systems to lower RA-related costs, enhance patient access to biologic treatments and reallocate savings to other patient care aspects.

The prices of originator products have gradually decreased as a result of significant price differences that exist at launch between biosimilars and originators. Consequently, biosimilars offer an opportunity to increase competition and save costs for healthcare systems. In fact, budget impact assessments have indicated that the adoption of biosimilars may result in significant cost savings. The possible budget increases from expanding access to biologics and offering additional services to RA patients must be weighed against such cost savings.

But in order for biosimilars to be successfully adopted, concerns with legal and patent matters, market dynamics, physician and patient acceptability and regulatory issues must be addressed. Healthcare systems can optimize the economic benefits of biosimilars and strengthen their sustainability amidst escalating healthcare expenditures by enacting supportive policies, including the engagement of relevant stakeholders and the generation of real-world evidence. It is envisaged that the broader adoption of biosimilars will help to lessen the disparities in biologic treatment utilization and potentially reduce the financial and social burden of RA.

10. Future directions and recommendations

In order to optimize the economic benefits of biosimilars for the sustainability of healthcare systems, a number of approaches and recommendations may be worthwhile considering. To assist in the effective incorporation of biosimilars into clinical practice, these include policy initiatives, stakeholder engagement and ongoing research and monitoring.

Author contributions

CN and NK led the conception and design of the study; CN, JF and MT conducted the literature search and synthesized the information from the selected studies; CN drafted the manuscript; NK, JF and MT helped to critically revise the manuscript. All authors read and approved the final manuscript.