Safety and efficacy of infliximab and corticosteroid therapy in checkpoint inhibitor-induced colitis.

BACKGROUND: Cancer patients treated with immune check point inhibitors are at risk of developing severe colitis. However, the efficacy and safety of treatment of severe colitis is poorly understood. AIMS: To explore the safety and efficacy of infliximab and corticosteroids in severe immune-mediated enterocolitis (IMC) METHOD: We performed a nationwide retrospective cohort study on 140 cancer patients treated with infliximab due to IMC in Denmark from 2011 to 2021. RESULTS: The rate of complete remission with infliximab was 52% after one dose, increasing to 73% after two or more doses. Thirteen patients (10%) required additional treatment with vedolizumab. Patients were heavily exposed to corticosteroids and received a median accumulated dose of 3978 mg (interquartile range [IQR] 2552-6414). Age- and cancer-adjusted Cox regression analysis found that a high dose of prednisolone at start of tapering ≥75 mg/day was associated with increased mortality (HR 1.67, 1.04-2.69, p = 0.035). Patients responding to infliximab experienced an improvement of symptoms after 3 days (IQR 2-4) and complete remission after 31 days (IQR 14-61). Twenty-four percent required hospitalisation for infection during treatment for IMC, lasting 7 days (median). Secondary gastrointestinal infections occurred in 16%, with Clostridioides difficile being most common (64%). Further, 10% had a thromboembolic event during the first 90 days after infliximab treatment. CONCLUSIONS: Infliximab led to complete resolution of symptoms in 73% of patients with IMC. High prednisolone dose at tapering was associated with increased mortality rate and a high incidence of infections and hospitalisations in patients with severe IMC. We suggest optimised infliximab treatment before escalation of steroid doses.

Polymorphisms in the NFkB, TNF-alpha, IL-1beta, and IL-18 pathways are associated with response to anti-TNF therapy in Danish patients with inflammatory bowel disease.

BACKGROUND: Anti-tumor necrosis factor-α (TNF-α) is used for the treatment of severe cases of IBD, including Crohn's disease (CD) and ulcerative colitis (UC). However, one-third of the patients do not respond to the treatment. We have previously investigated whether single nucleotide polymorphisms (SNPs) in genes involved in inflammation were associated with response to anti-TNF therapy among patients with CD or UC. AIM: A new cohort of patients was established for replication of the previous findings and to identify new SNPs associated with anti-TNF response. METHODS: Fifty-three SNPs assessed previously in cohort 1 (482 CD and 256 UC patients) were genotyped in cohort 2 (587 CD and 458 UC patients). The results were analysed using logistic regression (adjusted for age and gender). RESULTS: Ten SNPs were associated with anti-TNF response either among patients with CD (TNFRSF1A(rs4149570) (OR: 1.92, 95% CI: 1.02-3.60, P = 0.04), IL18(rs187238) (OR: 1.35, 95% CI: 1.00-1.82, P = 0.05), and JAK2(rs12343867) (OR: 1.35, 95% CI: 1.02-1.78, P = 0.03)), UC (TLR2(rs11938228) (OR: 0.55, 95% CI: 0.33-0.92, P = 0.02), TLR4(rs5030728) (OR: 2.23, 95% CI: 1.24-4.01, P = 0.01) and (rs1554973) (OR: 0.49, 95% CI: 0.27-0.90, P = 0.02), NFKBIA(rs696) (OR: 1.45, 95% CI: 1.06-2.00, P = 0.02), and NLRP3(rs4612666) (OR: 0.63, 95% CI: 0.44-0.91, P = 0.01)) or in the combined cohort of patient with CD and UC (IBD) (TLR4(rs5030728) (OR: 1.46, 95% CI: 1.01-2.11, P = 0.04) and (rs1554973)(OR: 0.80, 95% CI: 0.65-0.98, P = 0.03), NFKBIA(rs696) (OR: 1.25, 95% CI: 1.01-1.54, P = 0.04), NLRP3(rs4612666) (OR: 0.73, 95% CI: 0.57-0.95, P = 0.02), IL1RN(rs4251961) (OR: 0.81, 95% CI: 0.66-1.00, P = 0.05), IL18(rs1946518) (OR: 1.24, 95% CI: 1.01-1.53, P = 0.04), and JAK2(rs12343867) (OR: 1.24, 95% CI: 1.01-1.53, P = 0.04)). CONCLUSIONS: The results support that polymorphisms in genes involved in the regulation of the NFκB pathway (TLR2, TLR4, and NFKBIA), the TNF-α signalling pathway (TNFRSF1A), and other cytokine pathways (NLRP3, IL1RN, IL18, and JAK2) were associated with response to anti-TNF therapy. Our multi-SNP model predicted response rate of more than 82% (in 9% of the CD patients) and 75% (in 15% of the UC patients), compared to 71% and 64% in all CD and UC patients, respectively. More studies are warranted to predict response for use in the clinic.

[Fatal acute pancreatitis caused by severe hypertriglyceridaemia].

We report a case of fatal acute pancreatitis caused by severe hypertriglyceridaemia in a 27-year-old male who was treated with quetiapine. The blood samples were milk-like with markedly elevated triglycerides (> 55 mmol/l). Computer tomography revealed a severe pancreatitis without bile stones or cholestasis. In spite of treatment the patient's condition rapidly worsened and he died 48 hours after admission. We discuss the option of treating hypertriglyceridaemia-induced pancreatitis with apheresis.

Clinical information on admission is insufficient to determine the appropriate isolation regimen for acute gastroenteritis.

INTRODUCTION: The number of admissions for acute gastroenteritis (GE) is increasing. The majority of patients pass through a single high-flow emergency department (ED) area which increases the risk of spreading GE. The aim of this study was to determine the frequency and aetiology of GE for acutely admitted patients and to analyse their clinical information focusing on risk indicators of contagious aetiology and on the chosen isolation regime to determine if the GE required a contact precaution isolation regime. MATERIAL AND METHODS: This study included patients above 16 years of age who were admitted acutely within a one-year study period to a Danish hospital with a catchment population of 231,000 persons. The following items were analysed: information from the referring doctor, diarrhoea, nausea and vomiting and fever history, abdominal pain, prior antibiotics, co-morbidity, drugs, travel history, contagious contacts, general condition, vital values, isolation regime, final diagnosis and results of stool examination. RESULTS: Among 17,531 acute admissions, 1.6% had acute GE and 60% of these had stool examinations performed. Only 35% of the patients with GE had information about possible GE at referral. Short duration and vomiting may help to identify norovirus and antibiotic treatment within the last month to identify Clostridium difficile infections. All patients with highly infective GE were isolated under a contact precaution regime, but only one in four of the isolated patients were actually highly contagious. CONCLUSION: Acute GE is a prevalent condition in the ED; a number of patients are isolated unnecessarily, but it is difficult to assess correctly who should be isolated and who should not. We recommend that further studies be undertaken to define isolation criteria and to assess the usefulness of new rapid analysis modalities with a view to reducing the isolation period. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.