Biosimilars in Inflammatory Bowel Diseases: General Concepts and Clinical Implications

*Sabrina Rodrigues de Figueiredo, Ana Elisa Rabe Caon, Rogerio Saad Hossne, Fábio Vieira Teixeira, Sabine Murakami Winkler and Natália Sousa Freitas Queiroz*

## **Abstract**

The treatment of inflammatory bowel disease (IBD) has changed over time with the increasing use of biologics to achieve therapeutic goals. As a result, the cost of treatment increased considerably, making it necessary to develop strategies that could increase access to biological therapies. In this scenario, the biosimilars were developed with the aim of reducing costs, maintaining safety and efficacy compared to the originator. Initially, its use in IBD was based on the extrapolation of studies in other specialties, such as rheumatology. More recently, studies in inflammatory bowel disease have emerged, with favorable results for its use. It is known that there are still knowledge gaps in the use of biosimilars and more experience is needed to increase clinicians' confidence in their clinical practice. This chapter proposes a review of what is currently known about biosimilars in IBD. It discusses about aspects such as safety, efficacy, interchangeability, immunogenicity and switches.

**Keywords:** treatment, inflammatory bowel disease, biological therapies, biosimilar, the originator, safety, efficacy, interchangeability, immunogenicity, switch, adverse effects

## **1. Introduction**

Biologic therapies, notably the monoclonal antibodies, changed dramatically the scenario of inflammatory bowel diseases (IBD) treatment in the past years. However, such medications have high costs that can limit patient's access to them [1–3]. In 2016, monoclonal antibodies represented only 1% of all biologic medications distributed by the Brazilian Public Health System, but 32% of expenses in biologic products [4]. Additionally, evolving treatment goals for IBD patients aiming deep remission and mucosal healing increased the use of biologics in treatment algorithms [5]. As demand becomes greater and the patents of older biologic therapies are expiring, the interest in marketing comparable versions of the reference products (RP) also increases.

Biosimilars are biologic medications resembling the RP, without clinically significant differences in safety and efficacy. Biosimilars have the potential to expand access to

biological therapies due to price competition and cost savings [1–3]. An analysis elaborated by the Johns Hopkins Bloomberg School of Public Health found that biosimilar price represented 68% of the RP price for infliximab in 2018 in the US and estimated a saving of \$407 million to up to \$1.4 billion in the same year if full biosimilar substitution of infliximab was supported by all employers who self-insure health coverage [6].

Following the expiration of Remicade® patent, CT-P13 was the first infliximab biosimilar to be approved by European Medicine Agencies (EMA) in 2013 after two clinical trials. The studies PLANETAS and PLANETRA compared CT-P13 to the RP in patients with ankylosing spondylitis and rheumatoid arthritis, respectively [7, 8]. In April 2015, the Brazilian Health Regulatory Agency (ANVISA) approved the first biosimilar of infliximab, Remsima® (Celltrion) [9] and, since then, there are three infliximab and three adalimumab biosimilars approved in Brazil (AMGEVITA™, HYRYMOZ® and Xilbrilada®). **Tables 1** and **2** summarize all approved biosimilars from infliximab and adalimumab by FDA, EMA and ANVISA.

This chapter explores general concepts of biosimilars and their implications in clinical practice in the context of inflammatory bowel diseases (IBD) treatment. We aim to summarize the positions of various scientific associations in the IBD field with respect to biosimilars and provide real-life data regarding their effectiveness and safety in countries where they have been used. In addition, the authors will focus on relevant questions encountered in the clinic, including issues related to switch, biosimilar knowledge among IBD specialists and nocebo effect.


### **Table 1.**

*Biosimilars for adalimumab approved by health authority. Correct of February 2021.*


### **Table 2.**

*Biosimilars for infliximab approved by health authority. Correct of February 2021.*

*Biosimilars in Inflammatory Bowel Diseases: General Concepts and Clinical Implications DOI: http://dx.doi.org/10.5772/intechopen.100452*
