PTU-009 Upper gastrointestinal inflammation in patients with immune-checkpoint inhibitor induced diarrhoea

Abstract

moderate-to-severe disease. However, these drugs tend to perform less well in the maintenance of remission. Route of administration may influence efficacy and network meta-analyses of trial data indicate a superiority of intravenous drugs (IV; Infliximab; IFX) over subcutaneous (SC; adalimumab; ADA). We conducted a retrospective multicentre case-control study to compare the efficacy of these two drugs. Methods Patients administered IFX or ADA as their first biologic, identified from therapy databases of five UK hospitals, were included, if they had completed induction dosing and entered maintenance. Patients receiving IFX as 'rescue' therapy were excluded. Data was collected for pre-biologic disease activity (Simple Clinical Colitis Activity Index (SCCAI), Creactive protein and calprotectin) and throughout anti-TNF therapy. The primary end-point for comparison was the number of patients in clinical remission at 52 weeks (combined features of continuing IFX or ADA therapy and SCCAI score £3). Data was collected for duration of therapy, or up to last follow-up, if beyond 52 weeks. Results 78 IFX (40.3±14.6 years, 33F) and 63 ADA (36.8 ±14.6 years, 27F) patients were analysed. There were no statistically significant differences in demographics or pre-biologic disease activity between the two groups. At 52 weeks, 58 (74%) IFX patients and 29 (46%) ADA patients remained on therapy (p=0.009) and in remission (26 (33%) vs 5 (8%), p=0.0003). Primary non response was the reason for treatment cessation in 15 (24%) ADA patients and 4 (5%) IFX patients (p=0.0012). Conclusions Our results from a real-world cohort mirror those produced in the network meta-analyses of clinical trials for these agents, suggesting that IFX is superior to ADA in UC maintenance of remission, demonstrated by improvement in SCCAI scores and treatment continuation at 52 weeks. There were no significant differences in colectomy rates, hospital admission for acute flares or adverse events in the study timeframe.

British Society of Gastroenterology endorsed guidance for the management of immune checkpoint inhibitor-induced enterocolitis

“…In another series, inflammatory changes in the upper GI tract were common in 40 patients with ICPi-induced diarrhoea who underwent OGD and included gastritis (40%) and duodenitis (17.5%). Importantly, even in the absence of macroscopically visible disease, there was a significant burden of microscopic inflammation especially in the duodenum (28%) 50 , which most commonly comprised chronic lymphocytic inflammation and/or increased intraepithelial lymphocytes (86%) with villous atrophy present in 71% 50 . The high yield of inflammatory disease observed in the upper GI tract of patients with upper GI symptoms justifies investigation with OGD and biopsy.…”

Atezolizumab, a PD-L1 Inhibitor: An Association of Bleeding Gastric Ulcer With Its Use

“…Irshaid et al demonstrated that upper GI inflammation is similar to Helicobacter pylori gastritis and celiac disease with minor variations on histology [9]. Above studies support immune dysregulation and activation of T cell lymphocytes as a possible mechanism for the development of upper GI ulcer with ICIs [7][8][9].…”

“…Tang et al in their study of 60 patients with endoscopy and biopsy showed a correlation between ICIs and upper GI inflammation after ruling out other risk factors [ 7 ]. Fazal et al in their study of 25 patients showed common upper GI features, which include erythema, edema, and friability [ 8 ]. Irshaid et al demonstrated that upper GI inflammation is similar to Helicobacter pylori gastritis and celiac disease with minor variations on histology [ 9 ].…”

Pathology of immune-mediated tissue lesions following treatment with immune checkpoint inhibitors

“…Additional findings in the upper GI tract include lymphocytic gastritis (>30 intraepithelial lymphocytes per 100 epithelial cells). In the duodenum, as well as chronic inflammation with a neutrophil, lymphocyte and plasma cell infiltrate, villus blunting and atrophy have also been described [7, 17].…”