The Efficacy of Currently Licensed Biologics for Treatment of Ulcerative Colitis: A Literature Review

Abstract

Biologics have been emerging as promising therapies in ulcerative colitis (UC) patients who are refractory to conventional medical treatment. This literature review aims to appraise the existing evidence on the efficacy and safety of NICE approved biological therapies, of which there are currently five licensed drugs, available for the treatment of UC in adults. An initial search was performed using National Institute of Clinical Excellence (NICE) guidelines. A further literature search of EMBASE, MEDLINE, Science Direct and Cochrane Library databases was done, resulting in a total of 62 studies being included in this review. Recent and seminal papers were included. Inclusion criteria for this review were adult participants and English papers only. In most studies, anti-tumour necrosis factor ɑ (TNFɑ) naïve patients were found to have improved clinical outcomes. Infliximab was found to be highly effective in inducing short-term clinical response, clinical remission as well as mucosal healing. However, loss of response was common and dose escalation was often required for achievement of long-term efficacy. Adalimumab was found to have both short-term and long-term efficacy which was also supported by real-world data. Golimumab was shown to have comparable efficacy and safety profiles to other biologics, although lack of therapeutic dose monitoring and loss of response is a barrier to optimising golimumab treatment efficacy. Vedolizumab was shown to have higher clinical remission rates when compared to adalimumab in a head-to-head trial, and the most cost-effective biologic when calculating quality-adjusted life years. Ustekinumab was found to significantly improve clinical remission rates in UC patients who were previously unresponsive to other biological treatments. However, as this is a newly licensed drug, there is limited literature currently available. Further, head-to-head studies are required to help determine the optimal treatment for patients with UC. With patents expiring, the development of biosimilars will help to reduce costs and increase the availability of these drugs to patients.

Keywords: adalimumab (humira); clinical trial & pharmacovigilance; golimumab; infliximab biosimilar; ulcerative colitis (uc); ustekinumab; vedolizumab.

Figure 1. A visual representation of the mechanism of action of the NICE approved biologics.

The cytokine TNFα plays a major role in the mediation of systemic inflammation in ulcerative colitis (UC). Infliximab, adalimumab and golimumab are monoclonal antibodies belonging to the class of anti-TNFα drugs [5]. They bind with a high affinity to TNFα, preventing it from binding to its receptor, thus neutralising its biologic activity and limiting inflammation [5]. Vedolizumab is another monoclonal antibody belonging to the class of anti-integrin drugs [5]. It primarily works by targeting and blocking α4β7 integrin [5]. This interferes with the migration of leukocytes to sites of inflammation and prevents further perpetuation of the inflammatory cycle [5]. Ustekinumab is an immunoglobulin (Ig)G antibody belonging to the class of anti-interleukin (IL)-12/23 drugs [5]. The cytokines IL-12 and IL-23 are both upregulated in UC [5]. Ustekinumab binds to the p40 protein subunit present in these cytokines and blocks their activity [5]. The image is created using Biorender.com.

Figure 2. PRISMA flowchart of search methodology.

PRISMA: Preferred Reporting Items for Systemic Reviews and Meta-Analysis