Japanese Trial Supports Widespread Use, Safety of Infliximab Biosimilar Use

For people with rheumatoid arthritis who have achieved clinical remission, the decision to switch from an originator biologic to a biosimilar is a critical one for both their health and the sustainability of health care costs.¹ A new clinical trial from Japan has provided valuable evidence for this exact scenario, showing that patients who switched from originator infliximab to a biosimilar maintained their remission and stability, with minimal adverse events.²

A recent Japanese study confirms that switching from originator infliximab to biosimilars maintains remission in rheumatoid arthritis patients, enhancing treatment accessibility. | Image credit: Valentina - stock.adobe.com

The study, known as the IFX-SIRIUS study I, was a 24-week, open-label, single-arm clinical trial that evaluated the efficacy and safety of a nonmedical switch from originator infliximab to the biosimilar CT-P13. While previous research had explored the safety of such switches using clinical disease activity indices, the authors of the study sought to provide a more robust analysis by incorporating high-sensitivity imaging modalities, such as musculoskeletal ultrasound (MSUS), along with clinical indices and serum biomarkers. According to the study's authors, this approach allowed for a more accurate and objective evaluation of disease activity at the joint level, providing an additional layer of confidence in the outcomes.

The study enrolled 19 patients with rheumatoid arthritis from 19 centers in Japan, with 18 patients included in the final analysis. The patient population had a median age of 63 years, and two-thirds of the participants were female. They had a median disease duration of 9 years and were on originator infliximab for a median of 6.4 years. A key inclusion criterion was that all patients were in a state of clinical remission, defined as a Disease Activity Score 28 (DAS28)-erythrocyte sedimentation rate of less than 2.6 at baseline. All patients were also taking methotrexate at the time of the switch.

The primary end point of the study was the proportion of patients who experienced a clinical relapse during the 24-week follow-up period. Of the 18 patients evaluated, 2 experienced a clinical relapse, which accounted for an 11.1% relapse rate. One patient relapsed at week 11 and the other at week 24, at which point they were discontinued from the study.

Beyond the primary end point, the study's secondary findings provided a compelling case for the biosimilar's efficacy. For the 17 patients who completed the study, there were no significant changes observed in the MSUS scores, including total grayscale and power Doppler scores. Clinical assessments also confirmed sustained remission, with no notable changes in key indices such as DAS28-ESR, DAS28-C-reactive protein, or the Health Assessment Questionnaire-Disability Index. Furthermore, the researchers found no apparent changes in the serum levels of multiple cytokines and chemokines, nor in other biomarkers like rheumatoid factor and anticyclic citrullinated peptide antibodies.

Safety data from the study also supported a positive outcome. Three nonserious adverse events were reported across the 18 patients: 1 case of eczema, 1 of dry dermatitis, and 1 of COVID-19. All were considered moderate in severity, and none resulted in a patient discontinuing the study.

"This study highlighted the potential for cost-effective biosimilars to maintain remission in patients with rheumatoid arthritis, suggesting significant implications for reducing treatment costs and improving accessibility," stated the authors in their conclusion.

From a managed care perspective, these findings are highly valuable. The high cost of originator biologics has been a persistent barrier to access and a driver of health care costs. The Japanese government, for instance, has actively promoted the use of biosimilars, citing the significant cost reduction—up to 38% compared with the originator in Japan as of December 2024—as a key factor in reducing national health care expenditures.³ The IFX-SIRIUS study provides a new layer of clinical data that supports the efficacy and safety of biosimilars in a real-world setting, potentially easing any remaining physician or payer caution about their use and addressing concerns about the nocebo effect.²

Although the results are promising, the study's authors acknowledged several limitations. The small sample size of 18 patients meant that the initial plan to test for noninferiority could not be completed, and the analysis was limited to estimations. Additionally, the 24-week follow-up period was relatively short, and further studies are needed to assess long-term outcomes.

Despite these limitations, the authors maintained that the prospective evaluation using multiple assessment methods—clinical, imaging, and biomarkers—gives the results considerable clinical value for managed care organizations and health care providers considering the nonmedical switch to biosimilars for patients who are already in remission.

References

1. Kvien TK, Betteridge N, Brüchmann I, et al.Beyond cost: observations on clinical and patient benefits of biosimilars in real-world settings. BioDrugs. 2025;39(4):537-553. doi:10.1007/s40259-025-00727-z

2. Xia L, Miao G, Yang X, et al. Efficacy and safety of SYSA1902 versus reference ustekinumab in moderate-to-severe plaque psoriasis: a multicenter, randomized, phase III study. J Am Acad Dermatol. 2025;93(1):115-123.  doi:10.1016/j.jaad.2025.03.018

3. Shimizu T, Kawashiri S-y, Koga T, et al. Switching from originator infliximab to biosimilar infliximab in Japanese patients with rheumatoid arthritis achieving clinical remission (the IFX-SIRIUS study I): an interventional, multicenter, open-label, single-arm clinical trial with clinical, ultrasound and biomarker assessments. Drug Discov Ther. Published online August 22, 2025. doi:10.5582/ddt.2025.01044