Post-Marketing Pooled Safety Analysis for CT-P13 Treatment of Patients with Immune-Mediated Inflammatory Diseases in Observational Cohort Studies

Abstract

Background At EU marketing authorisation, safety data for CT-P13 (biosimilar infliximab) were limited, particularly in some indications, and uncommon adverse events (AEs) could not be evaluated among relatively small analysis populations. Objectives Our objective was to investigate the overall safety profile and incidence rate of AEs of special interest (AESIs), including serious infections and tuberculosis, in CT-P13-treated patients. Methods Data were pooled from six observational studies representing authorised indications of CT-P13 (ankylosing spondylitis, rheumatoid arthritis, psoriatic arthritis, plaque psoriasis, adult and paediatric Crohn's disease and ulcerative colitis). Patients were analysed by indication and treatment (patients who received CT-P13 or those who switched from reference infliximab to CT-P13 ≤ 6 months prior to enrolment or during the study). Results Overall, 4393 patients were included (n = 3677 CT-P13 group; n = 716 switched group); 64.03% of patients had inflammatory bowel disease and 6.31% of patients were antidrug antibody positive. Overall, 32.94% and 9.58% of patients experienced treatment-emergent AEs (TEAEs) and treatment-emergent serious AEs, respectively. Across indications, TEAEs were more frequent with CT-P13 than with the switched group. Infections including tuberculosis were the most frequent serious AESI overall (2.48%) and by treatment group or indication. In total, 14 patients (0.32%) reported active tuberculosis. Overall incidence rates per 100 patient-years (95% confidence interval) were 3.40 (2.788-4.096) for serious infections including tuberculosis and 0.44 (0.238-0.732) for active tuberculosis. Infusion-related reactions were the second most frequent AESI following infection including tuberculosis. ConclusionThe CT-P13 safety profile appears consistent with previous studies for CT-P13 and reference infliximab, supporting the favourable risk/benefit balance for CT-P13 treatment.

Post‐marketing analysis for biosimilar CT‐P13 in inflammatory bowel disease compared with external data of originator infliximab in Japan

“…The risk of tuberculosis associated with anti‐TNF therapy has been extensively investigated, and the incidence was shown to be independent of disease type (CD or UC), age, and sex, but related to the local prevalence of latent tuberculosis and poverty. 9 , 12 , 16 , 34 The tuberculosis burden in Japan is intermediate, and 14 tuberculosis cases (0.28%) were reported in 5000 Japanese patients with rheumatoid arthritis in a large‐scale PMS of the originator IFX. 35 Among them, 11 cases occurred in the first 2000 patients just after the introduction of IFX into the Japanese market, but the incidence was reduced to three per the remaining 3000 patients because of appropriate instruction regarding examinations and prophylactic drug use.…”

“…12 , 13 , 14 Higher risk of tuberculosis associated with originator IFX in Asian countries was well investigated, 15 but information on CT‐P13‐associated tuberculosis risk and hepatotoxicity in Asian patients with IBD is insufficient. 16 Therefore, it is especially important to explore the safety profile of CT‐P13 including tuberculosis risk and hepatic injury in this region.…”

Impact of Infliximab Biosimilar CT-P13 Dose and Infusion Interval on Real-World Drug Survival and Effectiveness in Patients with Ankylosing Spondylitis

“…Taken together, the sample size and setting provide good representation of biologic-treated patients with AS in the Republic of Korea. Safety analyses were not conducted as part of this investigation; however, previous reports have demonstrated the safety of CT-P13 treatment for patients with AS or spondyloarthritis, including after switching from reference infliximab [ 2 , 20 , 24 , 25 , 35 ].…”

Anti-drug antibodies and rheumatoid factor level in patients with rheumatoid arthritis using the infliximab biosimilar CT-P13

“…The emergence of anti-drug antibodies (ADAs) with neutralizing activities has been a concern when using CT-P13 as well as IFX originator drug [ 1 – 3 , 6 , 7 ]. The prevalence of ADAs in patients receiving IFX therapy has been reported to range from 15 to 54% [ 3 , 6 , 8 , 9 ].…”