Shifting knowledge and attitudes about biosimilars among rheumatologists

This editorial refers to ‘US rheumatologists’ beliefs and knowledge about biosimilars: a survey’, by Allan Gibofsky and Dorothy McCabe on pages 896--901.

Rising biologic drug costs pose serious, ongoing threats to the health and financial well-being of people with rheumatic diseases in many areas of the world. As drug costs have increased, national healthcare budgets have strained, and some patients face escalating insurance premiums and out-of-pocket costs. In a 2019 study by the American College of Rheumatology, 60% of US patients with rheumatic disease said they had difficulty affording medications although nearly all had insurance [1]. As a US rheumatologist, I have often seen these disturbing access and affordability issues profoundly impact the lives of patients, with some foregoing paying bills to pay for medications, and cost-related non-adherence resulting in declining function, pain and work disability. A decade ago, there was great hope that biosimilars would provide some relief for escalating biologic drug costs. Unfortunately, the arrival of biosimilars has only partially alleviated cost concerns since both uptake and cost savings have been uneven across the world.

In this issue of the journal, Gibofsky and McCabe report on a survey that investigated the knowledge and views of 320 US rheumatologists regarding biosimilars [2]. While earlier studies conducted in the USA and elsewhere found that many rheumatologists were reluctant to prescribe biosimilars, this new study suggests that views are shifting [3, 4]. Most US rheumatologists (73%) reported that they were likely or very likely to prescribe a biosimilar for a biologic-naïve patient. Interestingly, acceptance of biosimilars was higher for initial prescribing than for switching, likely reflecting that clinicians still have concerns about bioequivalence and are reluctant to change therapies in patients who are doing well. While it is true that biologic drugs do not have fully reproducible structures given factors such as protein glycosylation, research to date has been extremely reassuring. For example, a recent systematic review examining 90 studies across 14 disease indications and over 14 000 participants found that most studies did not report differences in biosimilar immunogenicity, safety or efficacy compared with originator drugs [5]. In the USA, the Food and Drug Administration (FDA) has instituted additional requirements beyond what is required for initial biosimilar approval to designate interchangeability. No biosimilar drugs have achieved this designation yet, a factor that has likely contributed to slower US uptake.

Gibofsky and McCabe also found that knowledge regarding biosimilars is higher among physicians than in previous surveys. Eight in ten respondents were familiar or very familiar with how the FDA defines a biosimilar. Not surprisingly, knowledge of FDA approval was higher for drugs available in US markets (infliximab biosimilars, 96%) compared with those that are approved but not yet available for rheumatology indications (etanercept, adalimumab and rituximab biosimilars, 62%, 56% and 39%, respectively). Some gaps in knowledge were also apparent. For example, one in five rheumatologists reported that they were likely or very likely to switch a patient not doing well on a reference biologic to its biosimilar, suggesting a lack of understanding that biosimilars should have equivalent (but not improved or different) efficacy. These findings are important and timely given that physician knowledge about biosimilars has rarely been systematically assessed. Results indicate that biosimilar knowledge and acceptance among US rheumatologists are higher relative to previous assessments and identify areas to target for continuing medical education. In addition, the results highlight the growing discordance between physician acceptance of biosimilars and the extremely low rate of biosimilar utilization across the USA.

Indeed, biosimilar uptake for rheumatic diseases in the USA has been extremely low. Ten years ago, the US Congressional Budget Office (CBO) projected cost savings of 40% for biosimilars in the USA. In European marketplaces, these estimated cost-savings are not far off and biosimilar sales have rapidly expanded, resulting in robust cost reductions. Countries like Denmark and Sweden, using the negotiating and purchasing power of their single-payer systems, have instituted a winner-takes-all bidding system for biosimilars. Denmark realized a two-thirds cost savings through this bidding process coupled with mandatory switching [6]. In contrast, the USA was projected to save $1 billion in 2018 due to biosimilars, but only achieved $91 million of cost-savings or just 9% of CBO projections [7]. In a recent analysis of 1.1 million infliximab prescriptions in a large commercial health plan between 2016 and the first quarter of 2019, <1% of prescriptions were for biosimilar infliximab vs the bio-originator drug, and cost-savings were very modest [8]. Data from the national RISE registry in the USA also demonstrated that biosimilar prescriptions reached a maximum of 3.5% of all TNF inhibitor prescriptions in 2018 across rheumatology practices nationwide [9]. Given the fragmented nature of payment systems in the USA, with hundreds of different insurance payers, achieving the negotiating power of single-payer systems in European countries will continue to be challenging.

What accounts for this growing disconnect between rheumatologists’ increasing acceptance of biosimilars and extremely low uptake in the USA? Multiple legal, financial and regulatory barriers have prevented a thriving US biosimilars market [1]. These include patent thickets that delay biosimilar launches, anti-competitive behaviours such as biologic manufacturers threatening to cancel existing price rebates if insurance plans add a biosimilar to their formulary, and evolving regulatory issues such as FDA policies around interchangeability [1]. Some have postulated that reluctance of US rheumatologists to switch to biosimilars is also a significant barrier. Although clinical inertia likely plays some role in low biosimilar prescribing, the study by Gibofsky and colleagues suggests it is unlikely that physician preferences are the primary contributor to poor uptake in the U.S. Instead, the global experience suggests that rheumatologists will adopt approved biosimilars if policies are aligned at the regulatory, insurance coverage and health delivery system levels.

It is important to note that the study by Gibofsky and McCabe has some limitations. First, the survey was conducted using a database of a popular medical website, Medscape.com, with enrolment limited to the first 360 eligible respondents. This non-random sample may not be representative of US rheumatologists if those with greater interest or knowledge of biosimilars responded to the survey. Also, physician survey responses are an imperfect proxy for prescribing behaviour.

The slow uptake and only modestly lower cost of biosimilars in the USA represent a significant missed opportunity. We now have a survey demonstrating that many US rheumatologists are willing to initiate biosimilars for people with rheumatic disease, and growing experience from around the world that patients have done well on these drugs. Unfortunately, the US experience has taught us that until the legal and regulatory barriers for biosimilars are surmounted, patients and taxpayers will continue to bear the burden of high biologic drug costs.

Acknowledgements

J.Y. is supported by the Alice Betts Endowed Chair in Arthritis Research, the Russel/Engleman Research Center at the University of California, San Francisco, and NIH/NIAMS P30 AR070155.

Funding: No specific funding was received from any funding agency in the public, commercial or not-for-profit sectors to carry out the work described in this manuscript.

Disclosure statement: J.Y. has received research consulting fees from Eli Lilly and Astra Zeneca unrelated to the manuscript.

Data availability statement

Data are available upon reasonable request by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). All data relevant to the study are included in the article.

References