Tag Archives: interchangeability

Interchangeability, Immunogenecity and Infliximab Biosimilars

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A recent study (G Fiorino et al. IBD 2018; 24: 601-6, editorial by KH Katsanos et al 465-6) provides more data on “full interchangeability” in regards to infliximab (IFX) and biosimilars CT-P13 and SB2. Full abstract below.

Key finding in study:

  • Antibodies to infliximab (ATI) cross-reacted with any type of IFX or IFX-biosimilar

Points from the editorial:

  • “The landmark NOR-SWITCH randomized controlled trial showed that 1-time switching from RMC [Remicade] to CT-P13 is not inferior to continued treatment with the infliximab originator…there are no data regarding multiple switches…Consequently, cross-switching (switching between 2 biosimilars), reverse switching (switching from biosimilar to its originator) or multiple/repeated switching is not currently recommended.”
  • This study, however, shows that “if you have already developed antibodies to 1 infliximab product, there is no point in switching to another infliximab product.”

Abstract:

Background: Infliximab (IFX) biosimilars CT-P13 and SB2 have comparable efficacy, safety, and immunogenicity to the originator Remicade (RMC). However, concerns about cross-switching patients between the 3 brands were raised in the absence of cross reactivity data between them. We aimed to determine whether antibodies to infliximab (ATI) in inflammatory bowel disease (IBD) patients cross-react with RMC, CT-P13, and SB2.

Methods: Based on previous ATI status, samples from 34 patients participating in the BIOSIM01 study (13 RMC, 9 CT-P13, and 12 switchers) were selected. Patients were treated with either RMC only, or CT-P13 only, or with RMC switched to CT-P13. Additionally, 28 IFX-naïve patients were assayed as controls. In total, 180 samples were analyzed. ATI trough levels were measured in parallel with 3 different bridging Enzyme Linked Immunosorbent Assays constructed using the 3 drugs. Spearman’s coefficient and percentages of agreement were used to study the correlation between each assay.

Results: In total, 76 samples out of 152 IFX-treated patient samples were ATI-positive (30 RMC, 14 CT-P13, and 32 switchers). All resulted ATI-positive when either CT-P13 or SB2 bridging assays were used. The overall percentage of agreement was 100% when compared either with CT-P13 or SB2 assays. No significant differences were found among ATI levels and coefficients (Spearman’s 0.98 to 1.0, P < 0.0001).

Conclusions: ATI of RMC-treated, CT-P13-treated or RMC to CT-P13 switched patients show full cross-reactivity with CT-P13 and SB2. Findings suggest that immunodominant epitopes in the reference and CT-P13 drugs are equally present in SB2. Data support full interchangeability between biosimilars in regard to immunogenicity.

My take: In patients doing well with IFX, switching to a biosimilar is not currently recommended.  In patients naive to IFX, use of IFX or biosimilar is expected to have similar efficacy.

Related study: B Kang et al. IBD 2018; 24: 607-16.  This prospective study of 36 pediatric patients did not identify any significant differences in efficacy…or immunogenicity after switching from IFX to CT-P13.

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Pediatric Views on Biosimilars and Interchangeability

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A recent commmentary (D Patel, KT Park. JPGN 2017; 134-6) explains the topic of interchangeability and its relationship to biosimlars. While biosimilars are expected to reduce the cost of biologic therapy, there are concerns regarding immunogenicity and whether switching to these products could reduce therapeutic sustainability.

The authors explain that some products are truly interchangeable and produce the same clinical result.  An interchangeable medicine (eg. typical generic) does not increase safety risk and switching from originator drug can be done by pharmacists or government payers without intervention of the prescribing health provider.

CT-P13 (Inflectra) has been approved as a biosimilar but has not been deemed an interchangeable product.  This is important.  Biosimilars “could have clinical consequences and repeated switches may increase immunogenicity.” Also, biosimilar products are much more complicated products than typical generic drugs.

Other key points:

  • The assumption that CT-P13 is interchangeable in pediatric IBD is “highly debatable.” Biosimilars undergo fewer studies than originator products.  CT-P13 has data from PLANETRA and PLANETAS trials “which may not be applicable for IBD, particularly pediatric IBD, given the inherent differences in disease pathophysiology.”
  • “No long-term, multiple-switch (eg. originator to biosimilar to originator) studies in pediatric or adult patients have been performed.”
  • “It is premature and possibly risky to assume that interchangeability will not cause differences in immunogenicity without long-term evidence in the pediatric population.” Pediatric patients likely have a “higher probability of developing autoantiantibodies” and need effective therapy for a longer duration.

My take: We still have a lot to learn.  Until more studies are available, switching stable patients could increase risk of losing response.

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