Changes in Anthropometric Parameters After Anti-TNFα Therapy in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis

Background: Tumour necrosis factor (TNF)-α inhibitors have been widely used for the treatment of moderate-to-severe inflammatory bowel disease (IBD). TNFα also plays an important role in the regulation of weight homeostasis and metabolism and has been linked to variations in anthropometric responses. This relationship in patients with IBD has yet to be determined. Objectives: Our objective was to evaluate the effects of TNFα inhibitors on changes in anthropometric measures in both adults and children with IBD through a systematic review and meta-analysis. Methods: Multiple database searches identified studies involving children and adults with IBD and treated with TNFα inhibitors and reporting at least one primary outcome measure. Where possible, data were combined for meta-analysis. The primary outcomes included weight, body mass index (BMI), waist circumference, height, height/velocity, and fat and lean mass. Secondary outcomes included surrogate markers of disease activity. A random-effects model was used to estimate the standardised mean difference (SMD). Results: In total, 23 cohort studies (total 1167 participants) met the inclusion criteria. Meta-analysis was performed on 13 of these studies. In children, 6–29.3 months of anti-TNFα therapy had a small but statistically significant effect on weight (SMD 0.31; 95% confidence interval [CI] 0.12–0.49; P = 0.001) with a mean gain in z score of 0.30 (standard error [SE] 0.12). In adults, 2–22.4 months of treatment had a moderate effect on BMI (SMD 0.72; 95% CI 0.17–1.26; P = 0.010; mean gain 1.23 kg/m2; SE 0.21). A small but statistically significant increase in BMI z score was found in children (SMD 0.28; 95% CI 0.03–0.53; P = 0.026; mean change 0.31 ± standard deviation [SD] 0.14) after 12–29.3 months of therapy. A meta-analysis of four studies found a negligible but statistically significant increase in height (SMD 0.16; 95% CI 0.06–0.26; P = 0.002; mean change 0.17 z score [SE 0.05]). A negligible effect on fat mass (SMD 0.24; 95% CI −0.19–0.66; P = 0.272) was found in a meta-analysis of five studies. Of note, despite the high heterogeneity among the studies that addressed the issue, these results were also consistently supported by findings from studies not included in the meta-analysis and reviewed in the systematic review. Unfortunately, a lack of data meant we were unable to perform moderator analysis on observed heterogeneity. Conclusion: Anti-TNFα treatment appears to be associated with an increase in body weight, BMI, and other anthropometric parameters. Given the differing courses of IBD between children and adults, this association should be considered before initiating biologics for undernourished, overweight, and obese patients. Registration: PROSPERO registration number CRD42020163079

Hyponatremia following Antipsychotic Treatment: In Silico Pharmacodynamics Analysis of Spontaneous Reports from the US Food and Drug Administration Adverse Event Reporting System Database and an Updated Systematic Review

Background: Hyponatremia associated with antipsychotic drugs is a rare but potentially life-threatening adverse drug reaction; the underlying pharmacological mechanism has not yet been explained. Methods: We investigated the relationship between pharmacological targets of antipsychotic drugs and the occurrence of hyponatremia by conducting a nested case-control study using the Food and Drug Administration Adverse Event Reporting System database. Multiple logistic regression was used to determine the associations between antipsychotics receptor occupancy and hyponatremia. We also performed a systematic review of clinical studies on this association. Results: Of 139 816 reports involving at least 1 antipsychotic, 1.1% reported hyponatremia. Olanzapine was the most frequently suspected drug (27%). A signi ?cant positive association was found between dopamine D3, D4, and hyponatremia, while adrenergic α 1, serotonin 5-HT1A, and 5-HT2A receptor occupancies were negatively associated. A multivariable stepwise regression model showed that dopamine D3 (adj. odds ratio = 1.21; 95% CI = 1.09-1.34; P <. 05) predicted the risk for hyponatremia (P <. 05), while serotonin 5-HT2A occupancy (Adj. odds ratio = 0.78; 95% CI = 0.68-0.90; P <. 01) exhibited a protective effect against hyponatremia. Among the 11 studies included in the systematic review, incidence rates of hyponatremia diverged between 0.003% and 86%, whereas the odds of developing hyponatremia from effect studies ranged between 0.83 and 3.47. Conclusions: Antipsychotic drugs having a combined modest occupancy for D3 and 5-HT2A receptors and higher levels of D3 receptor occupancy correspond to different degrees of risk for hyponatremia. Based on the few, relatively large-scale available studies, atypical antipsychotics have a more attenuated risk pro ?le for hyponatremia