The introduction of biosimilars into Australia was met with debate on whether the cost savings to the healthcare system would be at the expense of patient safety¹. Since then, clinicians have gained more experience with their use and the clinical evidence has grown, providing a better understanding of the efficacy and safety of these agents. On the eve of the biosimilars week we caught up with Melbourne gastroenterologist Dr. Britt Christensen about her experience using biosimilars in private and public practice.

Biosimilars in Australia: the gastroenterology experience

The biosimilar Inflectra was first included on the PBS in 2015 with the same listing as Remicade (infliximab) across all indications, including Crohn’s disease and ulcerative colitis.² This listing was estimated to result in around $100 million in savings in 5 years (due to the statutory 16% price reduction with the listing of a biosimilar).²

Consultant gastroenterologist Dr. Britt Christensen has experience with the use of biosimilars in both public practice at The Royal Melbourne Hospital and in her private practice in East Melbourne. Apart from the obvious cost savings, she counts the opportunity to expand clinical services as one of the main benefits resulting from the introduction of biosimilars.

“Biosimilars create competition in the marketplace, which means that manufacturers are more motivated to provide clinical services and support to patients. The lower cost doesn’t increase the number of patients we can treat with biosimilars, due to the PBS restrictions, but competition is always good because it leads to other benefits,” she says.

The cost savings when switching from the reference biologic to Inflectra at the Royal Melbourne Hospital allowed the hospital to employ an IBD pharmacist and an IBD fellow, who’s involved in both research and patient support, she explains. “This has made a huge difference to our unit,” she says.

Dr. Christensen says that private gastroenterologists are less likely to recognise any particular benefit from switching to a biosimilar, although the government has introduced incentives to do so.

The government uptake drivers for infliximab biosimilars include Streamlined Authorities, an advantage over the written Authority required for Remicade. “If a patient is currently on a biosimilar, the Department will provide a code for subsequent prescriptions, eliminating a lot of paperwork and the delay in the Authority approval. This cuts down time for the prescriber and also avoids the delay in providing the prescription to the patient. I’ve found that many private gastroenterologists are unaware of this benefit,” says Dr Christensen.

The growing evidence base for biosimilars

“Most clinicians working in academia would be quite comfortable with biosimilars because we’re aware of the latest evidence to support their efficacy and safety,” Dr Christensen explained.

This latest evidence includes a recent systematic review and meta-analysis³ of 11 observational studies in 829 patients with Crohn’s disease or ulcerative colitis, which found high clinical response rates and low rates of adverse events with Inflectra, as well as high sustained clinical response after switching from the originator biologic to Inflectra.

The effect of switching patients to a biosimilar

Much of the debate on the use of biosimilars often centres around the safety concerns of switching from the reference biologic to the biosimilar.⁴

In some countries, such as Denmark and Norway, switching is inevitable due to national single tenders for biosimilars.⁵ Similarly, some public hospitals choose to list only the biosimilar on their formulary as a cost-saving measure.

While there are arguments against single tenders – because they eliminate physician and patient choice as well as market competition⁵ – these situations do allow the opportunity for observational cohort studies and further real-world evidence on the efficacy and safety of switching patients currently on the reference biologic over to the biosimilar.

In Denmark, a nationwide move from originator infliximab (Remicade) to the biosimilar, along with the country’s national registry of patients on biologic therapies, allowed for an evaluation of the impact of the switch on a large cohort of patients with inflammatory arthritis. Data on 802 patients who switched to the biosimilar showed that it resulted in no negative impact on disease activity.⁶

A teaching hospital in the United Kingdom also investigated the outcomes of switching IBD patients from Remicade to the biosimilar. The observational study found that it delivered significant cost savings and investment in clinical services while maintaining similar patient-reported outcomes, biochemical response, drug persistence, and adverse event profile. There was also no increase in immunogenicity.⁷ A prospective cohort study in The Netherlands also found no significant impact on short-term clinical outcomes with a switch to the biosimilar in IBD patients.⁸

“From a clinical point of view, I have no significant concerns about using a biosimilar instead of the originator biologic,” says Dr. Christensen. “However, I’ll only switch patients once from either the originator biologic to a biosimilar or vice versa, and this is because there is evidence to support this switch. We still lack the evidence for multiple switches. Multiple switching will obviously be more of a concern as more biosimilar options enter the market,” she adds.

The NOR-SWITCH study published in The Lancet provides randomised, double-blind evidence of the effect of switching from Remicade to Inflectra in 481 patients across all indications.⁹

The study found that the switching from Remicade to the biosimilar Inflectra is not inferior to continued treatment with Remicade, according to a pre-specified non-inferiority margin of 15%. Stable patients switching to Inflectra experienced a similar percentage of disease worsening when measured across all indications, compared to those remaining on Remicade therapy.⁹

The sustainability argument

By 2020, there will be an estimated 100,000 Australians with IBD – a substantial increase compared to the 75,000 Australians with the condition in 2012¹⁰. While biologics have led to improved patient outcomes, their relatively high cost places a burden on the healthcare budget. Six of the ten most expensive medicines subsidised by the PBS in 2015–16 were biological medicines, with a combined cost of $1.28 billion.¹¹

Biosimilars are expected to deliver significant savings due to price competition, which the government argues can then allow reinvestment into other areas of the Australian health system and expanded access to biologic medicines as they become more affordable.¹¹ The availability of more than one biologic option also reduces the risk of supply shortages.¹¹

However, continued physician prescription choice of safe and high-quality biologic medicines is also important in maintaining a sustainable market. An analysis of how to ensure long-term sustainability in Europe⁵ has cautioned against restricting national access to one agent only because this could have a negative impact on physician choice, healthy competition, and continuity of supply.

Doctor Christensen agrees, believing that competition brings benefits to both the healthcare system and to patients. “I definitely would not like to see a single-tender approach in this country,” she says. “It’s important that the patient is included in the conversation, so that they’re aware of what you’re prescribing and the benefits to them,” she adds.

References

1. ARA position on the introduction of biosimilars for the treatment of rheumatic diseases (https://rheumatology.org.au/downloads/ARApositionstatementbiosimilarsNov16final.pdf
2. Public Summary Document (PSD) July 2015 PBAC Meeting: http://www.pbs.gov.au/info/industry/listing/elements/pbac-meetings/psd/2015-07/infliximab-psd-july-2015
3. Komaki Y, et al. Systematic review with meta-analysis: the efficacy and safety of CT-P13, a biosimilar of anti-tumour necrosis factor-µ agent (infliximab), in inflammatory bowel diseases. Aliment Pharmacol Ther. 2017 Apr;45(8): 1043–1057. https://www.ncbi.nlm.nih.gov/pubmed/28239873
4. Wiland P et al. Biosimilar switching – current state of knowledge. Reumatologia 2018;56,4:234–242. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6142020/
5. Advancing Biosimilar Sustainability in Europe. A Multi-Stakeholder Assessment. IQVIA Institute Report. September 4, 2018. https://www.iqvia.com/institute/reports/advancing-biosimilar-sustainability-in-europe
6. Glintborg B, et al. A nationwide non-medical switch from originator infliximab to biosimilar CT-P13 in 802 patients with inflammatory arthritis: 1-year clinical outcomes from the DANBO registry. Ann Rheum Dis 2017 Aug; 76(8): 1426–1431. https://www.ncbi.nlm.nih.gov/pubmed/28473425
7. Razanskaite V, et al. Biosimilar Infliximab in Inflammatory Bowel Disease: outcomes of a managed switching programme. J Crohns Colitis 2017 Jun 1; 11(6):690–696. https://www.ncbi.nlm.nih.gov/pubmed/28130330
8. Smits LJ, et al. Clinical outcomes following a switch from Remicade to the biosimilar CT-P13 in inflammatory bowel disease patients: a prospective observational cohort study. J Crohns Colitis 2016 Nov; 10(11):1287–1293. https://www.ncbi.nlm.nih.gov/pubmed/27095751
9. Jørgensen KK, et al. Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomised, double-blind, non-inferiority trial. Lancet 2017 Jun 10: 389(10086):2304–2316. https://www.ncbi.nlm.nih.gov/pubmed/28502609
10. Crohn’s Disease and Colitis Australia. Available at: https://www.crohnsandcolitis.com.au/site/wp-content/uploads/Fast-facts-about-IBD-20141.pdf
11. Factsheet for Healthcare Professionals. Infliximab Biosimilars on the Pharmaceutical Benefits Scheme. http://www.health.gov.au/internet/main/publishing.nsf/content/biosimilar-awareness-initiative/$File/Factsheet-for-healthcare-professionals-Biosimilar-infliximab-on-the-PBS.pdf