Comparative Analysis Supports Use of CT-P13, Interchangeability Remains a Challenge

The introduction of tumor necrosis factor (TNF) alpha inhibitors transformed treatment of conditions such as rheumatoid arthritis (RA), psoriatic arthritis, and ankylosing spondylitis (AS). TNF inhibitors have been shown in both studies and real-life experience to have favorable efficacy and safety profiles in these indications. However, the high costs of TNF inhibitors has led some countries to implement budget-restriction policies that potentially limit patient access to these drugs. Although the development of lower-cost biosimilars such as CT-P13 (the first biosimilar of infliximab introduced in the rheumatology field) can address unmet medical needs by widening access to expensive biological therapies, efficacy and safety concerns have been raised about potential differences between biosimilars and their reference products. Furthermore, recent surveys suggest that many physician specialists have only a basic knowledge of biosimilars; nearly a quarter cannot define or have not heard the term biosimilar.

Seeking to further clarify the use of biosimilars, Andrea Becciolini, MD, of the Department of Rheumatology, University of Milan, and coauthors conducted a comparability analysis of the infliximab biosimilar CT-P13 (Inflectra) and its reference product (Remicade). The analysis, which was published online in Drug Design, Development and Therapy, concludes that biosimilar CT-P13 is a valid treatment option for patients with RA and other rheumatologic conditions. “CT-P13 and [Remicade] showed a similar profile in terms of quality, biological activity, safety, immunogenicity, and efficacy,” the authors said, but they note that the issue of interchangeability between the reference infliximab and its biosimilar remains a challenge because of a lack of available long-term data.

The researchers evaluated equivalence randomized controlled trials (RCTs), including PLANETRA and PLANETAS. Their review explores the important findings from the literature concerning the following issues:

• Demonstrating the comparability of pharmacokinetics (PK) and pharmacodynamics (PD) for biosimilar and reference infliximab. The PLANETAS and PLANETRA studies confirmed the equivalence between CT-P13 and the reference infliximab in terms of PK and PD endpoints.
• Efficacy and safety comparability in AS and RA patients. The PLANETAS and PLANETRA studies showed that patients’ clinical response to CT-P13 stayed within the pre-established equivalence range obtained from the reference infliximab.
• Efficacy endpoints. The overall comparative experience of CT-P13 clearly demonstrated both short- and long-term clinical and radiographic progression equivalence between biosimilar and reference infliximab.
• Safety endpoints. The authors said that safety data from comparative studies of CT-P13 seem to be very reassuring, and that the safety profile of CT-P13 has been shown to be comparable with that of the reference product. However, post-approval pharmacovigilance will be crucial to assessing the risk of less common adverse events that may emerge with the biosimilar.
• Immunogenicity. The formation of antidrug antibodies (ADAs) can be associated with lower drug levels and clinical nonresponse, and infusion-related reactions are the most frequent potential safety consequences of biological drug immunogenicity. Studies showed no substantial differences in efficacy or ADA production between patients treated with reference infliximab versus those treated with CT-P13; while that is a reassuring finding, the researchers stress that a strict post-marketing pharmacovigilance program is needed to track any ADAs associated with biosimilars.
• Interchangeability and substitution. Key concerns remain about the interchangeability and substitution of biosimilars. Long-term, open-label extensions of comparative trials and real-life switching experiences have not shown unexpected differences in the efficacy, safety profile, and immunogenicity of patients who switched from reference infliximab to CT-P13 compared with the group treated with CT-P13 alone. However, the data are not adequate to completely satisfy new FDA study design requirements to show interchangeability. More data from switching studies will be necessary.

In conclusion, the researchers say that available data strongly confirm the equivalence of reference infliximab and CT-P13 from a PD and clinical point of view, and that the data are reassuring about the switching approach from the reference drug to biosimilar. “The findings suggest interchangeability between [Remicade] and CT-P13 as a feasible and safe strategy to be applied in real-life clinical practice,” the authors conclude. “Additional data from future clinical trials designed with the aim of specifically evaluating multiple interchangeability between [Remicade] and all its biosimilars should be advocated in order to improve our approach in the management of this condition.”