Immune checkpoint inhibitor-induced colitis is mediated by polyfunctional lymphocytes and is dependent on an IL23/IFNγ axis.

Immune checkpoint inhibitors (CPIs) are a relatively newly licenced cancer treatment, which make a once previously untreatable disease now amenable to a potential cure. Combination regimens of anti-CTLA4 and anti-PD-1 show enhanced efficacy but are prone to off-target immune-mediated tissue injury, particularly at the barrier surfaces. To probe the impact of immune checkpoints on intestinal homoeostasis, mice are challenged with anti-CTLA4 and anti-PD-1 immunotherapy and manipulation of the intestinal microbiota. The immune profile of the colon of these mice with CPI-colitis is analysed using bulk RNA sequencing, single-cell RNA sequencing and flow cytometry. CPI-colitis in mice is dependent on the composition of the intestinal microbiota and by the induction of lymphocytes expressing interferon-γ (IFNγ), cytotoxicity molecules and other pro-inflammatory cytokines/chemokines. This pre-clinical model of CPI-colitis could be attenuated following blockade of the IL23/IFNγ axis. Therapeutic targeting of IFNγ-producing lymphocytes or regulatory networks, may hold the key to reversing CPI-colitis.

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

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 É‘ (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.