Background: Pharmacogenomic testing guided treatment have been developed to guide drug selection or conversion in major depressive disorder patients. Whether patients benefit from pharmacogenetic testing remains unclear. We aim to evaluates the effect of pharmacogenomic testing guiding on clinical outcomes of major depressive disorder. Methods: Pubmed, Embase, and Cochrane Library of Clinical Trials were searched from inception until August 2022. Key terms included pharmacogenomic and antidepressive. Odds ratios (RR) with 95% confidence intervals (95%CIs) were calculated using fixed-effects model for low or moderate heterogeneity or random-effects model for high heterogeneity. Results: Eleven studies (5347 patients) were included. Compared with usual group, pharmacogenomic testing guided group was associated with an increased response rate at week 8 (OR 1.32, 95%CI 1.15–1.53, 8 studies, 4328 participants) and week 12 (OR 1.36, 95%CI 1.15–1.62, 4 studies, 2814 participants). Similarly, guided group was associated with an increased rate of remission at week 8 (OR 1.58, 95%CI 1.31–1.92, 8 studies, 3971 participants) and week 12 (OR 2.23, 95%CI 1.23–4.04, 5 studies, 2664 participants). However, no significant differences were found between the two groups in response rate at week 4 (OR 1.12, 95%CI 0.89–1.41, 2 studies, 2261 participants) and week 24 (OR 1.16, 95%CI 0.96–1.41, 2 studies, 2252 participants), and remission rate at week 4 (OR 1.26, 95%CI 0.93–1.72, 2 studies, 2261 participants) and week 24 (OR 1.06, 95%CI 0.83–1.34, 2 studies, 2252 participants). Medication congruence in 30 days was significantly reduced in the pharmacogenomic guided group compared with the usual care group (OR 2.07, 95%CI 1.69–2.54, 3 studies, 2862 participants). We found significant differences between subgroups of target population in response and remission rate. Conclusion: Patients with major depressive disorder may benefit from pharmacogenomic testing guided treatment by achieving target response and remission rates more quickly.

Cyclin-Dependent Kinase (CDK) 4/6 inhibitors have shown significant clinical activity in cancer patients. However, some concerns regarding rare adverse events (AEs) have occurred including interstitial lung disease (ILD)/pneumonitis, for which data are deficient. The aim of this study was to evaluate the overall incidence and risk of ILD/pneumonitis related to CDK4/6 inhibitors in randomized controlled trials (RCTs). Electronic databases and ClinicalTrials.gov were searched from inception to October 1, 2021 for RCTs reporting the occurrence of LD/pneumonitis in cancer patients treated with CDK4/6 inhibitors. Peto odds ratios (Peto ORs) and 95% confidence intervals (CIs) were used to pool the study. 12 RCTs with a total of 16,060 patients were eligible. The overall incidence of all-grade ILD/pneumonitis was 1.6% (131/8407) in the treatment group compared with 0.7% (50/7349) in the control group. CDK4/6 inhibitors significantly increased the risk of all-grade ILD/pneumonitis with a pooled Peto OR of 2.12 (95% CI [1.57, 2.86], P < 0.00001) with no heterogeneity (I² = 0%, χ² P = 0.98). A higher incidence of grade 3 or higher ILD/pneumonitis was also observed in the treatment group (0.2%, 16/7087) compared with the control group (0.05%, 3/6617) with a Peto OR of 3.22 (95% CI [1.28, 8.09], P = 0.01) with no heterogeneity (I² = 0%, χ² P = 0.62). Two grade 5 pneumonitis were reported in the included studies. Subgroup analyses did not show any significant difference. The risk of all-grade and grade 3 or higher ILD/pneumonitis was higher in patients treated with CDK4/6 inhibitors compared to controls. The awareness for these rare AEs in the application of CDK4/6 inhibitors should be enhanced. Further studies are required to validate the mechanisms and the risk factors of ILD/pneumonitis with CDK4/6 inhibitors.

Introduction: Enfortumab vedotin (EV) has been demonstrated to have a significant response rate in early phase trials and is known for its tolerable side-effect profile. Emerging case reports have raised awareness of cutaneous toxicities, which may be a potentially fatal complication. Objective: To assess the potential relevance between EV and cutaneous toxicities reports through data mining of the U.S. Food and Drug Administration (FDA) adverse event reporting system (FAERS). Methods: Data from January 1, 2019, to November 4, 2021, in the FAERS database were retrieved. Information component (IC) and reporting odds ratio (ROR) were used to evaluate the association between EV and cutaneous toxicities events. Results: EV was significantly associated with cutaneous toxicities in the database compared with both all other drugs (ROR 12.90 [10.62–15.66], IC 2.76 [2.52–3.01], middle signal) and platinum-based therapy (ROR 15.11 [12.43–18.37], IC 2.91 [2.66–3.15], middle signal) in the FAERS database. A significant association was detected between EV and all the cutaneous adverse effects (AEs) except erythema, palmar–plantar erythrodysesthesia syndrome, and dermatitis allergic. Both Stevens–Johnson syndrome and toxic epidermal necrolysis occurred 15 times as frequently for EV compared with all other drugs (ROR = 15.20; ROR = 15.52), while Stevens–Johnson syndrome occurred 18 times and toxic epidermal necrolysis occurred 7 times as frequently for EV compared with platinum-based therapy in the database (ROR = 18.74; ROR = 7.80). All groups that limited the gender and age showed a significant association between EV and cutaneous toxicities. Conclusions: A significant signal was detected between EV use and cutaneous toxicities. It is worth noting that Stevens–Johnson syndrome and toxic epidermal necrolysis were significantly associated with EV use.

Background Among patients who had an ischaemic stroke presenting directly to a stroke centre where endovascular thrombectomy (EVT) is immediately available, there is uncertainty regarding the role of intravenous thrombolysis agents before or concurrently with EVT. To support a rapid guideline, we conducted a systematic review and meta-analysis to examine the impact of EVT alone versus EVT with intravenous alteplase in patients who had an acute ischaemic stroke due to large vessel occlusion. Methods In November 2021, we searched MEDLINE, Embase, PubMed, Cochrane, Web of Science, clincialtrials.gov and the ISRCTN registry for randomised controlled trials (RCTs) comparing EVT alone versus EVT with alteplase for acute ischaemic stroke. We conducted meta-analyses using fixed effects models and assessed the certainty of evidence using the GRADE approach. Results In total 6 RCTs including 2334 participants were eligible. Low certainty evidence suggests that, compared with EVT and alteplase, there is possibly a small decrease in the proportion of patients independent with EVT alone (risk ratio (RR) 0.97, 95% CI 0.89 to 1.05; risk difference (RD) −1.5%; 95% CI −5.4% to 2.5%), and possibly a small increase in mortality with EVT alone (RR 1.07, 95% CI 0.88 to 1.29; RD 1.2%, 95% CI −2.0% to 4.9%) . Moderate certainty evidence suggests that there is probably a small decrease in symptomatic intracranial haemorrhage (sICH) with EVT alone (RR 0.75, 95% CI 0.52 to 1.07; RD −1.0%; 95%CI −1.8% to 0.27%). Conclusions Low certainty evidence suggests that there is possibly a small decrease in the proportion of patients that achieve functional independence and a small increase in mortality with EVT alone. Moderate certainty evidence suggests that there is probably a small decrease in sICH with EVT alone. The accompanying guideline provides contextualised guidance based on this body of evidence. PROSPERO registration number CRD42021249873.

Background The association between immune checkpoint inhibitors (ICIs) and thromboembolic events (TEEs) remains controversial. Objective The goal of this study was to assess the risk of major TEEs associated with ICIs. Methods We explored ICI-related TEEs in randomized controlled trials available in ClinicalTrials.gov and electronic databases up to June 30, 2021. Meta-analysis was performed by using Peto odds ratios (ORs) with 95% confidence intervals (CIs). Results A total of 61 studies were included. Patients treated with ICIs had a similar risk of venous thromboembolism (VTE) but a significantly increased risk of arterial thromboembolism (ATE) (Peto OR: 1.58 [95% CI: 1.21–2.06]) compared with non-ICI regimens. Stratified by different regimens, only PD-L1 (programmed cell death ligand 1) inhibitors showed a significant increase in ATE (Peto OR: 2.07 [95% CI: 1.26–3.38]). The incidence of VTE was higher in PD-1/PD-L1 inhibitor and CTLA-4 (cytotoxic T lymphocyte antigen 4) inhibitor combination therapies compared with monotherapies (Peto OR: 2.23 [95% CI: 1.47–3.37]). Stratified by tumor, for pulmonary embolism (PE) and cerebral ATE, the statistically significant results were only seen in lung cancer patients (Peto OR: 1.42 [95% CI: 1.02–1.97]; Peto OR: 2.10 [1.07–4.12]), and for myocardial infarction, the statistically significant result was only seen in other tumor types (Peto OR: 2.66 [95% CI: 1.68–4.20], p < 0.0001). Conclusion There was no significant increase in the overall risk of VTE in patients treated with ICIs; however, special attention should be given to the risk of VTE in PD-1/PD-L1 inhibitor and CTLA-4 inhibitor combination therapy and PE in lung cancer patients. PD-L1 inhibitors were associated with a significant increase in ATE. YH.Z. and ZL.A. were responsible for the conception and design of the study. Z.M. and XM.S. did the data extraction, statistical analysis, and drafted the original writing of the manuscript. Y.Z., H.L., and D.S. contributed to the methodological support. All authors contributed to the critical review and editing of the manuscript and approved the final version of the manuscript. ^* Zhuo Ma and Ximu Sun are first co-authors. Received: 20 December 2021 Accepted: 28 March 2022 Article published online: 30 June 2022 © 2022. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany