Background: Bevacizumab is used in the treatment of advanced malignancies and has a "black box" warning for gastrointestinal perforations. Despite this known side effect, there are no large descriptive series of patients who experience bevacizumabinduced gastrointestinal perforations. Aim:To review and describe post-market cases of bevacizumab-induced gastrointestinal perforation reported by healthcare professionals to the United States Food and Drug Association Adverse Event Reporting System (FAERS) database. Methods:In total, 74 025 cases of bevacizumab-induced adverse drug reaction were reported to FAERS from January 1 2004 to July 6 2021. We identified 2874 cases of bevacizumab-induced gastrointestinal perforation. A total of 1375 cases were determined to contain complete patient demographic data after the removal of duplicates and were reviewed. Subgroup analysis was completed on gastro-oesophageal perforations given the lack of prior data. Results:The average patient age was 61.9 ± 11.4 years. A total of 698 cases included descriptive locations of perforations with most occurring in the large intestine (385 cases, 55.2% of specifically described cases). Colorectal cancer was the most common indication for bevacizumab (691 cases, 50.3%) followed by ovarian cancer (197 cases, 14.3%) and non-small cell lung cancer (182 cases, 13.2%). Death was reported in 554 patients (40.3% of cases). Sixty-two cases of gastro-oesophageal perforation were identified.Conclusions: This is the largest collective descriptive study of bevacizumab-induced gastrointestinal perforations, and sheds light on this often fatal complication. We additionally identified and described a rare subgroup of patients experiencing bevacizumab-induced gastro-oesophageal perforation not previously described.

Wichelmann et al. This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 4.0., which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Background Osteonecrosis of the jaw (ONJ) is a rare but serious adverse drug reaction (ADR) commonly associated with bisphosphonate and denosumab therapy. Prior research utilized an online, public FDA Adverse Event Reporting System (FAERS) Database to explore this ADR. This data identified and described several novel medications associated with ONJ. Our study aims to build upon the prior findings, reporting trends of medication induced ONJ over time and identifying newly described medications. Methods We searched the FAERS database for all reported cases of medication related osteonecrosis of the jaw (MRONJ) from 2010 to 2021. Cases lacking patient age or gender were excluded. Only adults (18 +) and reports from Healthcare Professions were included. Duplicate cases were removed. The top 20 medications were identified and described for April 2010-December 2014 and April 2015-January 2021. Results Nineteen thousand six hundred sixty-eight cases of ONJ were reported to the FAERS database from 2010–2021. 8,908 cases met inclusion criteria. 3,132 cases were from 2010–2014 and 5,776 cases from 2015–2021. Within the cases from 2010–2014, 64.7% were female and 35.3% were male, and the average age was 66.1 ± 11.1 years. Between 2015–2021, 64.3% were female and 35.7% were male, and the average age was 69.2 ± 11.5 years. Review of the 2010–2014 data identified several medications and drug classes associated with ONJ not previously described. They include lenalidomide, corticosteroids (prednisolone and dexamethasone), docetaxel and paclitaxel, letrozole, methotrexate, imatinib, and teriparatide. Novel drugs and classes described between 2015–2021 include palbociclib, pomalidomide, radium 223, nivolumab, and cabozantinib. Discussion While stricter inclusion criteria and removal of duplicate cases led to fewer overall identified cases of MRONJ when compared to prior research, our data represents a more reliable analysis of MRONJ reports to the FAERS database. Denosumab was the most frequently reported medication associated with ONJ. While unable to imply incidence rates from our data due to the nature of the FAERS database, our findings provide further description of the various medications associated with ONJ and elucidate patient demographics associated with the ADR. Additionally, our study identifies cases of several newly described drugs and drug classes that have not been previously described in literature.

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Herpes simplex esophagitis (HSE) represents a rare entity in immunocompetent patients and has infrequently been described in association with eosinophilic esophagitis (EoE). Causality in this rare association remains a debated topic. We present a case of HSE occurring in an immunocompetent adult with EoE and review the literature in support of EoE induced mucosal disruption predisposing to increased risk of HSE.