Published online Dec 14, 2018. doi: 10.3748/wjg.v24.i46.5288
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
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.
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.
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
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.
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.
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.
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.