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Paper Proposes Methodology to "Protect Health Systems" That Use Biosimilars


A study published this month proposes that biosimilars be assessed in a quantitative benefit-risk analysis to assess whether what the authors call “uncertainty in the clinical performance of biosimilars” can be countered by lower pricing.

Development of biosimilars generally involves, as a culminating step, a confirmatory study in the most sensitive population in which the biosimilar is proposed for use. These confirmatory studies, which are undertaken after preclinical models have shown no differences between the biosimilar and its reference, and after pharmacokinetic and pharmacodynamic evaluation has been conducted, are intended to resolve any residual uncertainty that developers or regulators may have about the similarity of the proposed product and its reference. Developers then provide scientific justification to regulators for the extrapolation of indications to disease states other than the one studied in the confirmatory trial.

The extrapolation of indications means that fewer clinical data are available for a biosimilar’s use in some disease states at the time of its launch, and that fact has led some clinicians to voice concerns about using biosimilars in treating diseases in which they were not directly studied in a confirmatory trial. One stated concern related to biosimilars has been the potential risk for increased immunogenicity, though more than 10 years and 700 million patient days of experience with biosimilars have not yielded evidence of such a risk.1

A study published this month proposes that biosimilars be assessed in a quantitative benefit-risk analysis to assess whether “uncertainty in the clinical performance of biosimilars,” primarily with respect to a hypothetical immunogenicity risk, arising from the extrapolation of indications can be “countered by their lower pricing.”2

The paper, published in PharamcoEconomics, used a 1-year decision-analytic model developed for CT-P13 (Inflectra, Remsima), an infliximab biosimilar, for the treatment of Crohn disease (CD). According to the paper’s authors, immunogenicity is a special concern with infliximab in CD as opposed to other disease states.

The authors designed a model of 1-year cost-effectiveness from the UK National Health Service (NHS) perspective. A hypothetical cohort of new starts with moderate to severe CD was simulated through the model. Immunogenicity was a key modifier; the rate of development of antibodies to infliximab were derived from meta-analysis assessing the brand-name infliximab, Remicade. Costs were taken from a 2009 Markov model, adjusted for inflation, and from NHS reference costs.

The base-case analysis resulted in an expected 1-year quality-adjusted life-year (QALY) of 0.803 for both the biosimilar and for its reference, with expected 1-year costs of £18,087 (US $25,109) and £19,176 (US $26,620), respectively.

However, the authors write that, “assuming 50% of patients develop [antidrug antibodies, ADAs] for Inflectra, compared with 12.4% who develop [ADAs] from Remicade,” then the biosimilar would only remain the preferred infliximab option if it were priced below £410 (US $498) per vial, versus £420 (US $510) per vial for the reference. The authors also put forth what they call a worst-case scenario in which 100% of patients exposed to the biosimilar develop ADAs, in which case the price for the biosimilar would need to drop to £395 (US $480) per vial to remain a preferred treatment. (However, the authors acknowledge that a recent head-to-head study of CT-P13 versus its reference in patients with CD, published in The Lancet, did not show any difference between the biosimilar and its reference in the population of patients with CD.3)

According to the current study’s authors, their model provides a basis for the quantitative evaluation of biosimilars to support health technology assessments, and can be used to “protect health systems” from “potential risks of biosimilars” when indications are extrapolated.


1. Cohen HP, Blauvelt A, Rifkin RM, Danese S, Gokhale SB, Woollett G. Switching reference medicines to biosimilars: a systematic literature review of clinical outcomes. [Published online March 3, 2018] Drugs. doi: 10.1007/s40265-018-0881-y.

2. Catt H, Bodger K, Kirkham JJ, Hughes DA. Value assessment and quantitative benefit-risk modelling of biosimilar infliximab for Crohn’s disease [published online August 2, 2019]. PharamcoEconomics. doi: 10.1007/s40273-019-00826-0.

3. Ye BD, Pesegova M, Alexeeva O, Osipenko M, Lahat A, Dorofeyev A. Efficacy and safety of biosimilar CT-P13 compared with originator infliximab in patients with active Crohn’s disease: an international, randomised, double-blind, phase 3 non-inferiority study [published online, March 28, 2019]. Lancet. doi: 10.1016/S0140-6736(18)32196-2.

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