Re: Lin I, Melsheimer R, Bhak RH, et al. Impact of switching to infliximab biosimilars on treatment patterns among US veterans receiving innovator infliximab. Curr Med Res Opin. 2022;38(4):613–627

Dear Editor,

We read the recent article by Lin et al. titled “Impact of switching to infliximab biosimilars on treatment patterns among US Veterans receiving innovator infliximab” with great interest. Infliximab (IFX) is an important tool in the treatment and maintenance of chronic inflammatory diseases (CIDs). Biosimilars are similar agents to their corresponding biologic agents and offer potential alternatives to the costly originators. In this study, the authors utilized the national Veteran Health Administration (VHA) datasets to conduct a retrospective cohort study comparing veterans with CIDs on IFX originator (termed continuers) with those who were switched to IFX biosimilars from IFX originator (termed switchers). The authors concluded that patients who switch from innovator to biosimilar IFX were more likely to discontinue treatment and switch to another innovator biologic (or switch back to innovator IFX) compared with continuers. While the study design and inclusion of stable patients are two high points of this article and should be noted, we had some concerns with the methods and conclusions, as noted below.

The authors observed 77.8% of switchers vs. 20.7% of continuers were switched to another innovator biologic (HR [95% CI] = 4.99 [4.26–5.84]; p<.001). The majority (>70%) of IFX users in the dataset were for inflammatory bowel disease. As researchers and providers at the VHA, this observation is not in line with our clinical experience. About 91% of switchers who switched to another innovator biologic were switched back to innovator IFX. The design and definition of a medication switch inherently favors the continuer group. In the continuer group, the only medication switch that was included was a change to a non-IFX innovator biologic. Continuers who were switched to a biosimilar IFX were censored and were unable to achieve the primary outcome of the switch to new innovator IFX inherently favoring the continuer group. The VHA policy during the study period included systemic switching from innovator IFX to a biosimilar. This is reflected by a longer post-index follow-up for switchers (737 d vs. only 479 for continuers) due to censoring in the continuer group. A total of 363 individuals (42.8% of the cohort) were censored in the continuer group which a sizable portion of the cohort. By censoring their data, a significant proportion of potential medication discontinuations are removed from the continuer cohort. The shorter follow-up time in the continuer group and the fact that a large portion of the continuer group was censored likely result in an underestimation of the discontinuation rate of continuers compared to switchers. The observation that only 9% of switchers compared with 20% of continuers were switched to a new non-IFX innovator biologic despite a longer follow-up time suggests that patients in the switch group did not develop higher rates of loss of response to IFX, although indirect comparison of rates should be performed with caution. The results of this study are based on extracted datasets and were not validated by chart review. An adequate review and assessment of switches needed to be conducted. Without that, there is a high likelihood that the information could be incorrect relying solely on data analysis which is liable to coding errors. Lastly, while noted in the declaration of funding, it is important to highlight that the study was funded by Janssen Scientific Affairs and the first author and most of the study team are either employees of Janssen Scientific Affairs or paid consultants by Janssen. Janssen Biotech is the maker of innovator IFX (Remicade). This association creates a potential for conflicting interests.

This study may give readers the impression that biosimilars may not be as efficacious as the originator. However, there have been multiple studies demonstrating the efficacy and safety of IFX biosimilars. Two randomized controlled trials published by Park et al. and Yoo et al. in 2013 and 2016, respectively, showed similar pharmacokinetics, safety profiles, and efficacy of CT-P13 (IFX dyyb), an IFX biosimilar, to IFX originator^1,2. The trial “Switching from originator IFX to biosimilar CT-P13 compared with maintained treatment with originator infliximab” (NOR-SWITCH), published in 2017, compared patients who continued on IFX originator to those who switched to CT-P13 (IFX dyyb)³. It found that switching to the biosimilar was non-inferior to continuing on IFX originator. There are potential concerns in NOR-SWITCH regarding trends toward more negative outcomes in Crohn’s disease patients after the switch, however, the difference was not statistically significant and the study was not powered to detect differences in different disease types and deserves further study for specific diseases. Biosimilars offer an opportunity through reduced costs to increase the availability of crucial drugs that have become a pillar in the treatment of many inflammatory conditions. We agree that there is still much to learn in terms of the use of biosimilars and their effectiveness in the treatment of CIDs, especially with newer biosimilars in development.

Transparency

Declaration of funding

The authors received no payment in preparation of this letter.

Declaration of financial/other relationships

J.H and A.W are supported by a grant from VA Health Services Research and Development [IIR 19-045]. J.H. is also supported in part with resources at the VA HSR&D Center for Innovations in Quality, Effectiveness and Safety [#CIN 13-413], at the Michael E. DeBakey VA Medical Center, Houston, TX (Hou). J.H. has received research funding from Redhill Biosciences, Janssen, Abbvie, Celgene, Genentech, Eli-Lily, Lycera, and Pfizer Inc.