medwireNews: In the “Great Debate” session at the 2017 ACR/ARHP Annual Meeting in San Diego, California, USA, two experts discussed whether patients with rheumatic diseases who are treated with biologic DMARDs should switch to biosimilar agents, focusing on efficacy, safety, and cost.
Are biosimilars comparable to their reference drugs?
Arguing for biosimilar use, Jonathan Kay (University of Massachusetts Medical School, Worcester, USA) told delegates: “The papers support that it is safe and effective and cost-effective to switch to a biosimilar.”
He emphasized that such agents must undergo rigorous laboratory and clinical evaluation to ensure they are highly similar to their reference products, and noted the growing number of biosimilars that have been approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), including infliximab, etanercept, adalimumab, and rituximab biosimilars.
Although biosimilars are not identical to their originator drugs, Kay explained that all biologics are subject to batch-to-batch variability, and presented the results of chromatographic analyses demonstrating that the biosimilar agents CT-P13 (infliximab-dyyb) and adalimumab-atto are comparable to different batches of their respective reference products in terms of molecular variability.
He then outlined the results of several randomized trials demonstrating similar efficacy, safety, and immunogenicity profiles of biosimilar agents and their originator products, including NOR-SWITCH, which demonstrated that the overall response to CT-P13 treatment was noninferior to the response to originator infliximab among patients with six inflammatory diseases.
Why do patients discontinue biosimilars?
Kay also discussed the results of the BIO-SWITCH study, which demonstrated that around a quarter of Dutch patients discontinued treatment with CT-P13 within 6 months of switching from originator infliximab, mainly due to subjective measures of disease activity. He believes that this substantial discontinuation rate can be attributed to the “nocebo effect” – misattribution of bodily symptoms to a drug – and stressed that reassurance, collaborative discussion, and encouragement are needed to address this.
On the other side of the coin, Roy Fleischmann (University of Texas Southwestern Medical Center, Dallas, USA) argued that patients discontinued biosimilar agents in a number of studies due to lack of clinical response rather than subjective measures. For example, in the DANBIO study of non-medical switching in Denmark, 16% of 802 patients who switched from infliximab to CT-P13 discontinued treatment over 413 days of follow-up, 54% of whom did so due to lack of effectiveness.
He also noted that although the NOR-SWITCH study demonstrated overall noninferiority of CT-P13 and originator infliximab, the results “were inconclusive” for patients with rheumatoid arthritis and psoriatic arthritis.
“You want to call it nocebo, or you want to call it the data?” he asked. “For many patients, you can do the switch, but not for every individual patient.”
Are biosimilars cost-effective?
Both presenters focused on cost and availability as one of the primary considerations when deciding whether to prescribe a biosimilar.
Fleischmann underlined that “if it isn’t considerably cheaper to the patient and society, there is no value in using a biosimilar.” He explained that in the current US healthcare system, insurance companies and other organizations may benefit from the use of biosimilars, but there is “no cost advantage and no increased access” for individual patients.
Nonetheless, Kay contended that in most settings, it is cost-effective to switch to a biosimilar.
“We are in the United States, but many faces in the audience are from Europe, South America, and Asia, so we need to take a global perspective on biosimilars,” he said.
Kay gave the example of Norway, in which CT-P13 was 69% cheaper than originator infliximab in 2015, and explained that use of the biosimilar increased following this time point. Furthermore, “[a]vailability of biosimilars introduces market competition that drives down the cost of biopharmaceuticals,” he said.
However, Fleischmann argued that the payer, and not the patient, saved money in the Norwegian example, and that biosimilars are not cheaper than their reference products in many countries.
He concluded by presenting the results of a survey showing that the largest proportion of rheumatologists would use biosimilars “only when forced to,” with smaller proportions willing to do so after 1 year, when others use them, or “as soon as possible.”
Practical advice
In response to a question from an audience member who asked what practical advice the experts have for physicians who are preparing patients for the switch to a biosimilar agent, Fleischmann said “if you’re going to do a switch, you need to be able to communicate to the patient what you expect from that switch,” but he thinks that more data are needed to be certain that efficacy and safety profiles will be maintained after the switch.
And Kay believes that “[i]f you inform the patient, educate them, and allow them to participate in the decision […] then negative responses and the nocebo effect [when switching to a biosimilar] will be minimized.”
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