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Caroline Hroncich was associate editor for Pharmaceutical Technology, Pharmaceutical Technology Europe, and BioPharm International from 2015 to 2017.
A study published in BMJ indicates that rheumatic patients with anti-infliximab antibodies may have a similar cross reaction to infliximab biosimilars.
The results of a BMJ study presented on June 10, 2016 at the European League Against Rheumatism Annual Congress (EULAR 2016) suggest that rheumatic patients with anti-infliximab (IFX) antibodies may have a cross-reaction with infliximab biosimilars-notably Remsima (infliximab) and Inflectra (infliximab)-leading to a loss of clinical response. However, the study also confirms these patients will also experience a similar loss of response with the branded product if anti-IFX antibodies are present. A EULAR press release promoting the data, titled “Biosimilar Switching Not Suitable for All Patients,” seemed to suggest that switching to a biosimilar of infliximab compounded the adverse effects associated with taking the branded medication.
Hubert Chen, MD, chief medical officer at Pfenex, told Pharmaceutical Technology that patient use of either branded infliximab or biosimilar infliximab would most likely lead to a similar clinical outcome. Biosimiliars are highly similar to their reference products and do not have any clinically meaningful differences from their reference products in terms of safety, efficacy, potency, or purity, Chen noted. In fact, a separate paper also presented at EULAR showed that switching to biosimilar infliximab did not change the number of flare ups experienced by patients. According to the study, approximately 10% of patients with rheumatoid arthritis experienced a flare-up both before and after switching to a biosimilar.
According the Chen, the EULAR announcement "seems to imply that patients who develop antibodies against branded infliximab should not switch to a biosimilar version of infliximab, because such a transition may potentially accelerate the loss of response. In reality, the continued use of either branded or biosimilar infliximab would have the same clinical effectâ¦[H]ence, if a patient were to develop antibodies when treated with a reference product, it should not be a surprise to expect those antibodies to cross-react against a biosimilar product that is highly similar,” said Chen. In fact, evidence of cross-reactivity may actually serve to confirm the similarity of a biosimilar to a reference product. Chen added, “It is reassuring, though, that such antibodies have not been associated with safety or tolerability issues in switching studies performed with branded and biosimilar infliximab, to date.”
Daniel Nagore, one of the BMJ study authors, told Pharmaceutical Technology, “If antibodies are formed against Remicade, or the patient does not respond, it does not make sense to switch to the biosimilar or to stay on Remicade, but [they instead should switch] to another drug (e.g., adalimumab or etanercept).” Therefore, patients who experience a loss of response using a drug sharing a mechanism of action with infliximab may want to look into other treatment options, he clarified. The BMJ research was originally published in March 2016.
Debate over the safety of biosimilar switching came to a head earlier this year when FDA released its guidance on biosimilar labeling. The agency indicated that biosimilar labels should contain reference product information. Some groups, including the American College of Rheumatology, spoke out saying they are concerned displaying reference product clinical trial information on biosimilar labels and not designating unique names for biosimilars may imply interchangeability. The college released a statement to FDA on the draft guidance encouraging FDA “to continue to apply distinct names for future biosimilars, and to maximize clarity in the labeling of biosimilars, specifically with respect to their interchangeable status and origins (reference drug versus biosimilar) of clinical data upon which FDA approval is based.” FDA has yet to make any comment on its view of the interchangeability of biosimilars and reference products.