PROTOCOL: A systematic review of clinical practice guidelines on managing immune checkpoint inhibitor-related gastrointestinal and hepatic toxicities: Quality of treatment recommendations and differences in management strategies between guidelines.
Creators: name: Hyeree Jang
name: Sail, Reena
name: DONKOR, KOFI N
Publisher: name: Open Science Framework
Year: 2023
Subjects: subject: Medicine and Health Sciences

description: Immune checkpoint inhibitor (ICI)-related gastrointestinal (GI) toxicities like celiac disease, cholangitis, cholecystitis, diarrhea/colitis, duodenitis, enterocolitis, esophagitis, gastritis, mucositis, nausea, pancreatitis, and hepatic toxicities have occurred in patients following checkpoint blockade.1-5 Colitis and diarrhea are the most frequently reported ICI-related GI toxicities. Symptoms occur more frequently in patients treated with anti-CTLA4 agents than those treated with anti-PD1/PDL1 agents.1 However, the highest incidence of colitis and diarrhea occurs in patients treated with a combination of anti-CTLA4 and anti-PD1/PDL1. Symptoms typically develop 6 to 8 weeks from treatment initiation with the incidence of colitis ranging from 8% to 27%, and the frequency of diarrhea in patients treated with anti-CTLA4, ranging from 30% to 40%. Some reports have values greater than 50%, particularly in patients treated with anti-CTLA4 and anti-PD1/PDL1 combinations. Incidences of both colitis and diarrhea are less common in anti-PD1 or PDL1 monotherapy, with diarrhea occurring in less than 19% of treated patients.1, 7-10 Checkpoint-associated liver toxicities like hepatitis have a median time to onset between 5 to 6 weeks, and an incidence ranging from 2% to 10% of patients treated with anti-CTLA4, anti-PD1, or anti-PDL1 monotherapy. An incidence of 25% to 30% of all-grade hepatitis and approximately 15% of grade 3 hepatitis has also been reported in patients treated with anti-CTLA4/ PD1 combinations.1, 7, 9, 11 Not enough data are available to give accurate reports on the exact incidences of less commonly occurring checkpoint-associated toxicities in the upper GI tract (nausea, gastritis, duodenitis, esophagitis), the gallbladder (cholecystitis), bile duct (cholangitis), the small intestines’ lining (celiac disease), and the pancreas (pancreatitis). Clinical Practice Guidelines (CPGs) are a critical resource used by clinicians in managing immune-related adverse events (irAEs) caused by checkpoint blockade. Questions that therefore come up are whether there are CPGs available for managing the diverse types of GI toxicities and hepatic toxicities caused by the ICIs. Other questions are the number of high-quality CPGs available for treatment of ICI-related GI toxicities, and the quality of treatment recommendations for these CPGs. We addressed these questions by completing a systematic review (SR) of all available CPGs with recommendations on GI or hepatic toxicities caused by the ICIs. We used AGREE II (Appraisal of Guidelines, Research and Evaluation II) to appraise the quality of CPGs and AGREE-REX (Appraisal of Guidelines Research and Evaluation–Recommendations Excellence) to determine the quality of CPGs’ treatment recommendations.12, 13 Furthermore, we determined the number of high-quality CPGs. We investigated the correlation between CPG treatment recommendations and CPG quality. We also assessed the differences in treatment recommendations between high-quality CPGs and lower-quality CPGs.12, 14