Author: Al Ta'ani, Omar ; Sohail, Amir H ; Numan, Laith ; Jaber, Fouad ; Kilani, Yassine ; Hassan, Kamal ; Madi, Mahmoud Y ; Kiwan, Wissam ; Dahiya, Dushyant Singh ; Bilal, Mohammad ; Alsakarneh, Saqr

BACKGROUND AND AIMSBiliary drainage is vital in managing malignant biliary obstruction (MBO). Suprapapillary stenting has emerged as a viable alternative to transpapillary stenting and is performed using inside plastic (iPS) or metal stents (iMS). This meta-analysis aims to evaluate the outcomes of suprapapillary stent placement for MBO.METHODSThe Embase, PubMed, and Web of Science databases were systematically searched to include all studies published before September 31, 2023, that reported on the outcomes of suprapapillary stents placed for MBO. Using the random-effect model, the pooled, weight-adjusted event rate estimate for the clinical outcomes was calculated with 95% confidence intervals (CIs).RESULTSTwenty-eight studies were included, with a total of 1401 patients. The pooled clinical success rate was 98.9%. A subgroup analysis yielded non-significant differences between the iPS and iMS groups (99.3% vs. 98.6%, respectively; P = 0.44). The pooled incidence rate of adverse events (AE) with suprapapillary stents was 9.5%. In a subgroup analysis, the incidence of AEs with iPS was 10.7% compared to 9% in the iMS group without a statistical difference (P = 0.32). The most common adverse event was cholangitis (2.2%), followed by pancreatitis (1.1%), cholecystitis (0.5%), and bleeding (0.12%).CONCLUSIONWhen technically feasible, suprapapillary stenting for MBO is a viable endoscopic option with a high clinical success rate and acceptable adverse event rates. Both iPS and iMS exhibit similar efficacy.

01 Jun 2024·eBioMedicine

Dose adjustment of paroxetine based on CYP2D6 activity score inferred metabolizer status in Chinese Han patients with depressive or anxiety disorders: a prospective study and cross-ethnic meta-analysis

Article

Author: Liu, Zhongchun ; Guo, Jing ; Wang, Jun ; Ni, Ai-Hua ; Weng, Saizheng ; Sun, Xin ; He, Jiong ; Zhang, Yunshu ; Zhang, Yong ; Wang, Anzhen ; Zhang, Yuyanan ; Sun, Lidong ; Wang, Hua-Ning ; Yue, Weihua ; Kang, Zhewei ; Liao, Yundan ; Sun, Yaoyao ; Huang, Chengchen ; Wang, Kai ; Sun, Yutao ; Zhang, Jian-Min ; Kuang, Li ; Cao, Changbin ; Chen, Zhi-Yu ; Pan, Jiyang

BACKGROUNDUnderstanding the impact of CYP2D6 metabolism on paroxetine, a widely used antidepressant, is essential for precision dosing.METHODSWe conducted an 8-week, multi-center, single-drug, 2-week wash period prospective cohort study in 921 Chinese Han patients with depressive or anxiety disorders (ChiCTR2000038462). We performed CYP2D6 genotyping (single nucleotide variant and copy number variant) to derive the CYP2D6 activity score and evaluated paroxetine treatment outcomes including steady-state concentration, treatment efficacy, and adverse reaction. CYP2D6 metabolizer status was categorized into poor metabolizers (PMs), intermediate metabolizers (IMs), extensive metabolizers (EMs), and ultrarapid metabolizers (UMs). The influence of CYP2D6 metabolic phenotype on paroxetine treatment outcomes was examined using multiple regression analysis and cross-ethnic meta-analysis. The therapeutic reference range of paroxetine was estimated by receiver operating characteristic (ROC) analyses.FINDINGSAfter adjusting for demographic factors, the steady-state concentrations of paroxetine in PMs, IMs, and UMs were 2.50, 1.12, and 0.39 times that of EMs, with PM and UM effects being statistically significant (multiple linear regression, P = 0.03 and P = 0.04). Sex and ethnicity influenced the comparison between IMs and EMs. Moreover, poor efficacy of paroxetine was associated with UM, and a higher risk of developing adverse reactions was associated with lower CYP2D6 activity score. Lastly, cross-ethnic meta-analysis suggested dose adjustments for PMs, IMs, EMs, and UMs in the East Asian population to be 35%, 40%, 143%, and 241% of the manufacturer's recommended dose, and 62%, 68%, 131%, and 159% in the non-East Asian population.INTERPRETATIONOur findings advocate for precision dosing based on the CYP2D6 metabolic phenotype, with sex and ethnicity being crucial considerations in this approach.FUNDINGNational Natural Science Foundation of China; Academy of Medical Sciences Research Unit.

01 May 2024·Annals of the Rheumatic Diseases

Withdrawal of immunosuppressants and low-dose steroids in patients with stable IgG4-RD (WInS IgG4-RD): an investigator-initiated, multicentre, open-label, randomised controlled trial

Article

Author: Zhou, Jiaxin ; Peng, Linyi ; Zhao, Lidan ; Lu, Hui ; Peng, Yu ; Zhang, Wen ; Li, Jieqiong ; Chen, Xiaomei ; Wang, Fang ; Zhao, Yan ; Wu, Lijun ; Fei, Yunyun ; Nie, Yuxue ; Li, Mengtao ; Zeng, Xiaofeng

ObjectivesIgG4-related disease (IgG4-RD) is an immune-mediated, fibroinflammatory disease. Induction treatment with glucocorticoid (GC) is usually effective, but its tendency of relapse makes the strategy for maintenance treatment a challenge. The WInS IgG4-RD (withdraw immunosuppressants (IMs) and steroid in stable IgG4-RD) trial tested whether discontinuation of GC and IM was feasible in stable IgG4-RD.MethodsThe WInS IgG4-RD trial was a multicentre, open-label, randomised controlled trial. Patients with IgG4-RD receiving GC+IM as maintenance treatment with clinically quiescent disease for at least 12 months were randomised (1:1:1) into three groups: group 1: withdraw GC+IM; group 2: withdraw GC but maintain IM; group 3: maintain GC+IM. The primary outcome was the relapse rate of disease within 18 months. The secondary outcomes included the changes of IgG4-RD Responder Index (RI), Physician’s Global Assessment (PGA), serum IgG4 and IgG, as well as adverse events.ResultsOne hundred and forty-six patients were randomised, with 48 patients in group 1, 49 patients in group 2 and group 3, respectively. Within the 18-month follow-up period, disease relapse occurred in 25 out of 48 (52.1%) patients in group 1 vs 7 out of 49 (14.2%) in group 2 and 6 out of 49 (12.2%) in group 3 (p<0.001). The changes in RI and PGA were significantly higher in group 1 than in group 2 (p<0.001) or group 3 (p<0.001).ConclusionsThe maintenance of IMs, with or without low-dose GC, was found to be superior to withdraw GC+IM in preventing relapse for long-time stable IgG4-RD.Trial registration numberNCT04124861.

100 Deals associated with INO-2002

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Indication	Highest Phase	Country/Location	Organization	Date
Colitis, Ulcerative	Phase 1	US	Inotek Pharmaceuticals Corp.	-
Rheumatoid Arthritis	Phase 1	US	Inotek Pharmaceuticals Corp.	-

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