**2. Effectiveness and safety of biosimilars in IBD patients**

Biosimilar uptake is increasing worldwide and accumulating evidence has been demonstrating the efficacy and safety of these drugs for the treatment of IBD patients [10–16]. **Figure 1** illustrates biosimilars for infliximab and adalimumab in the pipeline.

However, most data on biosimilars in IBD originate from real-life experience after switching from a reference biologic to a biosimilar [17] and the available randomized controlled studies comparing the reference biologic and biosimilars often had a short-term follow-up [18].

Ye et al. conducted the first randomized, multicenter, double-blind, phase 3 and non-inferiority study evaluating the efficacy and safety of biosimilar CT-P13 compared with originator infliximab in patients with active Crohn's disease (CD). Patients were randomly assigned (1:1:1:1) to receive CT-P13 then CT-P13, CT-P13 then infliximab, infliximab then infliximab or infliximab then CT-P13, with switching occurring at week 30. The primary endpoint was the proportion of patients with a decrease of 70 points or more in the Crohn's Disease Activity Index (CDAI) at week 6. Response rates were similar between the two groups (CT-P13: 69.4%, CI 95%: 59.9–77.8 vs. IFX: 74.3%, CI 95%: 65.1–82.2), establishing the non-inferiority of CT-P13 in relation to IFX [18]. Accordingly, in a prospective, observational and multicentre study, Gecse et al. evaluated the efficacy, safety and immunogenicity of CT-P13 in the treatment of CD induction (*n* = 126) and ulcerative colitis (UC-*n* = 84). Remission, clinical and biochemical response were assessed at week 14, corticosteroid-free clinical remission at week 30 and therapeutic drug level was monitored. After 14 weeks of treatment, 81.4% of patients with CD and 77.6% of patients with UC presented clinical response and 53.6% of patients with CD and 58.6% of those with UC achieved clinical remission, according to the CDAI and partial Mayo score. The rates of clinical remission were higher in patients not previously exposed to IFX. Infusion reactions and serious adverse events occurred in 6.6% of patients with CD and 5.7% of patients with UC. The authors concluded that CT-P13 is safe and effective in inducing remission and clinical response in both CD and UC [19].

**Figure 1.** *Biosimilars for infliximab and adalimumab.*

A recent systematic review and meta-analysis by Queiroz et al. assessed the risk and reasons for drug discontinuation in the IBD population that switched from the originator to biosimilars in real-world studies [20]. A total of 30 observational studies comprising 3594 IBD patients who switched from originator biologics to biosimilar with a mean follow-up period over 6 months and a mean duration of treatment with the originator reported as over 1 year were included. In addition, the reasons for treatment discontinuation were extracted and meta-analyzed. The discontinuation rates after a switch were 8, 14 and 21% after 6, 12, and 24 months, respectively. The main reasons for discontinuation were as follows: increased loss of response (2%), remission (4%), loss of adherence (4%), adverse effects (5%) and loss of response (7%). Quality of evidence varied from low to very low depending on the analyzed outcome. The nocebo effect was explicitly analyzed as a reason for discontinuation in only one study [21], and the frequency of reported subjective adverse events was low. It is important to emphasize that most of the studies included in this review did not disclose important information that could have influenced the results, such as disease activity at the moment of switch and drug trough levels before and after switch. This study raises awareness for the urgent need to conducting prospective studies evaluating long-term outcomes associated with the switch of biological therapy in IBD patients.
