Adverse Event Reporting with Immune Checkpoint Inhibitors in Older Patients: Age Subgroup Disproportionality Analysis in VigiBase

Older patients represent a subpopulation of concern for immune checkpoint inhibitor (ICI) toxicity because of changes in the aging immune system and the potentially relevant clinical implications for their quality of life. Current evidence on ICI safety in older patients is conflicting. This study aimed to assess whether older patient age was a risk factor for increased reporting with ICIs as compared to other antineoplastic drugs in VigiBase, the World Health Organization database of suspected adverse drug reactions. Disproportionality analyses computing the reporting odds ratios (RORs) were performed by age subgroups (<18 years, 18–64 years, 65–74 years, 75–84 years and ≥85 years). There were not signals of disproportionate reporting with ICIs specifically detected in older patient age subgroups (≥65 years), which were not present in the disproportionality analysis over the entire dataset. A signal of disproportionate reporting with ICIs emerged for eye disorders only in the age subgroup 18–64 years (ROR 1.13, 95% confidence interval 1.05–1.23). These findings showed that adverse event reporting with ICIs in older patients was comparable to that in the overall patient cohort and prompt for the further investigation of eye disorders with ICIs to elucidating risk factors and defining management strategies

Adverse Event Reporting with Immune Checkpoint Inhibitors in Older Patients: Age Subgroup Disproportionality Analysis in VigiBase

Older patients represent a subpopulation of concern for immune checkpoint inhibitor (ICI) toxicity because of changes in the aging immune system and the potentially relevant clinical implications for their quality of life. Current evidence on ICI safety in older patients is conflicting. This study aimed to assess whether older patient age was a risk factor for increased reporting with ICIs as compared to other antineoplastic drugs in VigiBase, the World Health Organization database of suspected adverse drug reactions. Disproportionality analyses computing the reporting odds ratios (RORs) were performed by age subgroups (<18 years, 18–64 years, 65–74 years, 75–84 years and ≥85 years). There were not signals of disproportionate reporting with ICIs specifically detected in older patient age subgroups (≥65 years), which were not present in the disproportionality analysis over the entire dataset. A signal of disproportionate reporting with ICIs emerged for eye disorders only in the age subgroup 18–64 years (ROR 1.13, 95% confidence interval 1.05–1.23). These findings showed that adverse event reporting with ICIs in older patients was comparable to that in the overall patient cohort and prompt for the further investigation of eye disorders with ICIs to elucidating risk factors and defining management strategies

Comparative risk/benefit profile of biosimilar and originator erythropoiesis-stimulating agents (ESAs): data from an Italian observational study in nephrology

Purpose: The aim of this multicenter prospective study was to evaluate efficacy and safety of biosimilar erythropoiesis-stimulating agents (ESAs) vs originator, based on data from clinical practice in patients with chronic kidney disease (CKD). Methods: We collected data of the patients with diagnosis of CKD on conservative treatment from nine Italian structures. Patients were enrolled applying different exclusion criteria, and various individual parameters were registered at the beginning for descriptive analysis. Patients were treated with epoetin alfa, beta, and darbepoetin as originator and epoetin zeta as biosimilar. Hemoglobin levels have been analyzed at baseline and after 3, 6, and 12 months. Descriptive statistics were used to analyze the results. Results: At baseline, 47 patients were in the biosimilar group and 57 in the originator; the basal level of hemoglobin was similar between the groups (mean Hb 9.4 and 9.3 g/dL, respectively). Median age, weight, and comorbidities were almost comparable. After 3 months, 44 patients remained in the biosimilar group and 48 in the originator; hemoglobin increase was significantly greater in patients treated with biosimilar [absolute increase 1.6 vs 1.0 g/dL, p < 0.001]. After 6 and 12 months, number of patients fall furthermore. Hemoglobin levels increased more in the biosimilar group after 6 months (2.1 vs 1.1 g/dL, p < 0.001) and 12 months (2.0 vs 1.0 g/dL, p < 0.001). Conclusions: Biosimilar ESAs have similar risk/benefit profile compared to originators. Our data are in agreement with relevant scientific literature and, on the other hand, they are in contrast with common thought that considers biosimilar less efficacious and less safe than originators

Anti-inflammatory and analgesic amides: new developments

A series of substituted N-cycloalkyl benzamides, cinnamamides, and indole-3-carboxamides were synthesized and evaluated for their analgesic, antiinflammatory activities as well as for their gastrointestinal irritation liability. Indomethacin was used as reference drug in both tests. Compounds 1k, 1b, 1h, 1j, and 1g were the most active in the antiinflammatory paw edema inhibition test, with a sharply dose-dependent effect. In terms of the analgesic activity (acetic acid writhing test), the most active compound was 5a followed by 3a, but many other compounds were found to have a non-negligible potency. Even in this case, the effect was dose dependent

Antidepressant-Induced Acute Liver Injury: A Case-Control Study in an Italian Inpatient Population

Introduction: Pre-marketing clinical trials show that antidepressant-induced liver injury seems to be a rare adverse event. Because of short follow-up trial duration, the incidence of liver injury due to antidepressant use could be underestimated. Objectives: We aimed to quantify the risk of acute liver injury associated with antidepressant use through a caseâcontrol analysis among an inpatient population. Methods: A multicenter study was carried out in nine Italian hospitals from October 2010 to January 2014, within the DILI-IT (Drug-Induced Liver Injury in Italy) study project. After exclusion of all patients with a clear competing cause of liver injury, cases were defined as adults admitted to the hospital with a diagnosis of acute liver injury, while controls had any other acute clinical condition not related to the liver. Antidepressant exposure was evaluated within 90 days prior to the date of the first sign/symptom of liver injury. Odds ratio (OR) with 95% confidence interval (95% CI) was calculated as a measure of risk estimates for liver injury. Results: We included 17 cases exposed to antidepressants matched to 99 controls. According to the features of liver injury, all cases showed symptomatic liver function test abnormalities at hospital admission, with the main signs/symptoms represented by fatigue, nausea, asthenia, or dark urine. Citalopram was the antidepressant mostly involved in the increase of liver enzymes, mainly alanine aminotransferase. Compared with non-use, current use of antidepressants was associated with a significantly increased risk of liver injury (adjusted OR, ORADJ, 1.84; 95% CI 1.02â3.32). Specifically, an increased, but not significant, risk of developing liver injury was observed for citalopram, a selective serotonin-reuptake inhibitor (ORADJ1.82; 95% CI 0.60â5.53). Conclusion: The use of antidepressants is not as safe in terms of liver injury as expected; instead, the risk of antidepressant-induced liver injury is likely underestimated. The lack of significance does not reflect the absence of risk, but rather suggests the need to evaluate it in a wider setting of antidepressant users