Observational Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 14, 2018; 24(46): 5288-5296
Published online Dec 14, 2018. doi: 10.3748/wjg.v24.i46.5288
Loss of efficacy and safety of the switch from infliximab original to infliximab biosimilar (CT-P13) in patients with inflammatory bowel disease
María Fernanda Guerra Veloz, Federico Argüelles-Arias, Luisa Castro Laria, Belén Maldonado Pérez, Antonio Benítez Roldan, Raúl Perea Amarillo, Vicente Merino Bohórquez, Miguel Angel Calleja, Ángel Caunedo Álvarez, Ángel Vilches Arenas
María Fernanda Guerra Veloz, Federico Argüelles-Arias, Luisa Castro Laria, Belén Maldonado Pérez, Antonio Benítez Roldan, Raúl Perea Amarillo, Ángel Caunedo Álvarez, Department of Gastroenterology, University Hospital Virgen Macarena, Seville 41007, Spain
Vicente Merino Bohórquez, Miguel Angel Calleja, Pharmacy Unit, University Hospital Virgen Macarena, Seville 41007, Spain
Ángel Vilches Arenas, Preventive Medicine and Public Health, University Hospital Virgen Macarena, Seville 41007, Spain
Author contributions: Guerra Veloz MF did the study design, data analysis and writing up of the first draft of the paper; Argüelles-Arias F did the data analysis and patient recruitment, Castro Laria L and Maldonado Pérez B did the patient recruitment; Perea Amarillo R and Merino Bohorquez V did the Data collection; Caunedo Álvarez Á did the study design; Vilches Arenas Á did the data analysis.
Institutional review board statement: The study was approved by the Research Ethics Committee of the Virgen Macarena Hospital, Seville, Spain.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: Guerra Veloz MF, Castro Laria L, Maldonado Pérez B, Perea Amarillo R and Argüelles-Arias F have received financial support to attend scientific meetings from Kern Pharma. Benítez Roldán A, Merino Bohórquez V, Calleja MA, Caunedo Álvarez Á, and Vilches Arenas Á do not have conflict of interest.
Data sharing statement: No additional data are available.
STROBE statement: the guidelines of the STROBE Statement have been adopted
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author to: Federico Argüelles-Arias, PhD, Doctor, Professor, Department of Gastroenterology, University Hospital Virgen Macarena, Dr. Fedriani 3, Seville 41007, Spain. farguelles@telefonica.net
Telephone: +34-61-7348501
Received: August 29, 2018
Peer-review started: August 29, 2018
First decision: October 14, 2018
Revised: November 18, 2018
Accepted: December 7, 2018
Article in press: December 7, 2018
Published online: December 14, 2018
Processing time: 106 Days and 18.3 Hours
ARTICLE HIGHLIGHTS
Research background

Infliximab was the first monoclonal antibody against tumor necrosis factor alpha approved by the US Food and Drug Administration (United States FDA) and European Medicines Agency (EMA) in the treatment of inflammatory bowel disease (IBD). Despite the undoubted efficacy of this biological therapy, this biological agent is much more expensive than traditional treatments and, therefore, imposes a considerable burden on the national health system. However, with the recent expiration of its patent, biosimilar medicines have been developed. CT-P13 (Remsima® and Inflectra®) was the first biosimilar of infliximab approved by EMA and United States FDA for all indications of the originator product including IBD. The effectiveness in IBD is being debated due to the approval of this biosimilar was based on clinical trials in rheumatological diseases.

Research motivation

Some observational studies and real-life cohorts have been published on the efficacy and safety of the infliximab biosimilar in naive patients with IBD. Although not strictly necessary, there are few studies comparing efficacy and safety of the switch from infliximab original to infliximab biosimilar CT-P13 vs the maintenance of the infliximab original.

Research objectives

To compare the efficacy of infliximab biosimilar, against infliximab original, analyzing the loss of response of both at the 12 mo follow-up in patients with IBD

Research methods

An observational study of two cohorts has been conducted. One retrospective cohort that included patients with IBD treated with Infliximab original, and a prospective cohort of patients who were switching from infliximab original to infliximab biosimilar. 98 patients were included in each cohort. We had analyzed the overall efficacy and loss of efficacy in patients in remission at the end of one year after treatment with the original drug compared to the results of the year of treatment with the biosimilar. The efficacy was reported based clinical scores [Harvey-Bradshaw score (HB) ≤ 4 in patients with Crohn’s disease (CD) or partial Mayo score ≤ 2 in patients with ulcerative colitis (UC)] and biochemical test. Wilcoxon test, McNemar´s test and the Cochran Q test were used to compare the variables in both periods.

Research results

This study demonstrated the overall efficacy and the loss of overall efficacy for infliximab original and infliximab biosimilar were similar per year of treatment.

The loss of efficacy in patients who were in basal remission was 16.3% in the infliximab original vs 27.1% in the infliximab biosimilar. This 10.8% of difference in the loss of efficacy between the two groups did not show a statistical difference. No significant changes in disease activity, measured by HB in CD (P = 0.385) and Partial Mayo score in UC (P = 0.349) were observed between both groups. Significant changes in the median CRP level (95%CI) were observed between both groups (P = 0.014), nevertheless, it was always in remission (≤ 5 mg/dL). Adverse events were similar in both cohorts.

Research conclusions

Our study suggests that the overall efficacy and loss of treatment response with infliximab biosimilar (CT-P13) is similar to that observed with infliximab original in patients who were switching at the 12 mo follow-up. The high difference in the loss of efficacy shown in patients who were in basal remission with infliximab original vs infliximab biosimilar could be explained by the following: in our data we found the intervals of confidence in both groups were so high that it was impossible to obtain a statistical difference, and in other hand, nocebo is a concept that should be taken into account in our results. Many patients did not have enough confidence in the biosimilar the first year.

Research perspectives

Future prospective comparative studies with long-term follow-up are necessary to discriminate the loss of efficacy in patient who were switched to infliximab biosimilar.