Drugs in Research & Development最新文献

{"title":"Development of the Drug Product Formulation of the Bevacizumab Biosimilar PF-06439535 (Bevacizumab-bvzr).","authors":"Rebecca L Ingram,&nbsp;Sarah E Weiser","doi":"10.1007/s40268-023-00411-z","DOIUrl":"https://doi.org/10.1007/s40268-023-00411-z","url":null,"abstract":"<p><strong>Background: </strong>PF-06439535 (bevacizumab-bvzr; Zirabev^®) is a biosimilar of bevacizumab reference product (RP; Avastin^®). This study describes the formulation development for PF-06439535.</p><p><strong>Methods: </strong>PF-06439535 was formulated in several buffers and stored for 12 weeks at 40 °C to determine the optimal buffer and pH under stressed conditions. Subsequently, PF-06439535 at 100 and 25 mg/mL was formulated in a succinate buffer with sucrose, edetate disodium dihydrate (EDTA), and polysorbate 80, and in the RP formulation. Samples were stored at - 40 °C to 40 °C for ≤ 22 weeks. The physicochemical and biological properties relevant to the safety, efficacy, quality, or manufacturability were investigated.</p><p><strong>Results: </strong>When stored at 40 °C for 13 days, PF-06439535 demonstrated optimal stability in histidine or succinate buffers and was more stable in the succinate formulation than the RP formulation, under both real-time and accelerated stability conditions. There were no significant changes in the quality attributes of 100 mg/mL PF-06439535 after storage at - 20 °C and - 40 °C for 22 weeks, and there were no changes in the quality attributes of 25 mg/mL PF-06439535 after storage at 5 °C (recommended storage temperature). Changes were observed at 25 °C for 22 weeks or at 40 °C for 8 weeks as expected. No new degraded species were observed in the biosimilar succinate formulation compared with the RP formulation.</p><p><strong>Conclusions: </strong>Results demonstrated that 20 mM succinate buffer (pH 5.5) is the PF-06439535 preferred formulation, and that sucrose is an effective cryoprotectant for processing and frozen storage, and an effective stabilizing excipient for 5 °C liquid storage of PF-06439535.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":"23 1","pages":"55-64"},"PeriodicalIF":3.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/46/8f/40268_2023_Article_411.PMC9985529.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10846847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benefits of Hydroxychloroquine Combined with Low-Dose Aspirin on Pregnancy Outcomes and Serum Cytokines in Pregnant Women with Systemic Lupus Erythematosus.","authors":"Na Zhang,&nbsp;Hong-Xia Zhang,&nbsp;Yu-Wei Li,&nbsp;Yuan Li","doi":"10.1007/s40268-022-00408-0","DOIUrl":"https://doi.org/10.1007/s40268-022-00408-0","url":null,"abstract":"<p><strong>Background and objective: </strong>Systemic lupus erythematosus (SLE) is an autoimmune disease, with hydroxychloroquine being the main therapeutic agent for the treatment of SLE. This research explored the effects of hydroxychloroquine combined with low-dose aspirin on maternal and infant outcomes and cytokines of pregnant women with SLE.</p><p><strong>Methods: </strong>Ninety pregnant women with SLE were divided into the hydroxychloroquine (HCQ) group (45 cases) and the hydroxychloroquine combined with low-dose aspirin (HCQASP) group (45 cases) by random number table. Patients in the HCQ group were treated with oral administration of hydroxychloroquine, while patients in the HCQASP group were treated with low-dose aspirin based on oral administration of hydroxychloroquine. Pregnancy outcomes, fetal outcomes, and cytokine levels were statistically analyzed.</p><p><strong>Results: </strong>The HCQASP group had a significantly higher proportion of full-term pregnancies and a significantly lower proportion of hypertension, prematurity, and pregnancy loss than the HCQ group. Neonates in the HCQASP group also had significantly higher birth weights and Apgar scores and a significantly lower proportion of neonatal asphyxia than the HCQ group. After treatment, the HCQASP group had significantly higher interleukin (IL-2) and interferon (IFN)-γ levels and significantly lower IL-4 and IL-10 levels than the HCQ group.</p><p><strong>Conclusion: </strong>Hydroxychloroquine combined with low-dose aspirin can effectively improve the pregnancy outcomes of pregnant women with SLE by affecting the levels of T helper (Th) 2 and Th1 cytokines.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":"23 1","pages":"35-42"},"PeriodicalIF":3.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e6/35/40268_2022_Article_408.PMC9985524.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10833587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Nontrivial Analysis of Patient Safety Risk from Parenteral Drug- and Medical Device-Borne Endotoxin.","authors":"Edward C Tidswell","doi":"10.1007/s40268-023-00412-y","DOIUrl":"https://doi.org/10.1007/s40268-023-00412-y","url":null,"abstract":"<p><strong>Background: </strong>A thorough and systematic analysis of potential endotoxin-related safety issues from parenteral drugs and devices is important to ensure appropriate current Good Manufacturing Practices, compendial requirements, standards and regulatory guidance. Lately, the US Food and Drug Administration has been expecting pharmaceutical firms to apply an arbitrary safety factor to compendial compliant drug specifications for endotoxin, potentially causing manufacturing challenges, supply issues and additional unwarranted costs.</p><p><strong>Objective: </strong>The aim of this study was to evaluate data from three disparate sources over an extended period of time, from 2008 to 2021, to determine if there exists an industry-wide risk to patients from parenteral drugs and devices, thereby evaluating if changes to current Good Manufacturing Practices or compendial requirements are indeed warranted. Food and Drug Administration data from current Good Manufacturing Practices non-compliance observations, product recalls and the FDA Adverse Event Reporting System were used as the three sources of data.</p><p><strong>Methods: </strong>Parenteral products were separated into drugs and devices, potential endotoxin-related patient safety issues were characterised in terms of the available non-compliance information, the type and number of product recalls, and the type and number of potential adverse events. Descriptive statistics in Microsoft Excel 2019 and Pivot tables were used for the analysis and presentation of the data.</p><p><strong>Results: </strong>From 2011 to 2021, a total of 188 endotoxin-related current Good Manufacturing Practices compliance observations were recorded, 70% and 30% were associated with laboratory and manufacturing origins, respectively. Finished drug product testing accounted for 56% of these. In contrast, 95% of all endotoxin-related product recalls were associated solely with medical devices. Over the years 2008-2021, approximately 1.4% of all adverse events (23,663,780) were recorded with some reference to pyrexia (fever); however, there are sparse data categorically attributing this to the administration of parenteral drugs or devices or combinations of these possessing high levels of endotoxin.</p><p><strong>Conclusions: </strong>Analysis of data concerning drug- and device-borne endotoxin obtained from FDA data from current Good Manufacturing Practices non-compliance observations, product recalls and the FDA Adverse Event Reporting System demonstrated the absence of industry-wide issues with endotoxin contamination. Based upon these data, changes to current Good Manufacturing Practices and the compendial methodology of setting endotoxin specifications (and hence the compendial methodology of testing for endotoxins) are unwarranted.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":"23 1","pages":"65-76"},"PeriodicalIF":3.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e5/71/40268_2023_Article_412.PMC9985525.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10852179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quercetin Supplement to Aspirin Attenuates Lipopolysaccharide-Induced Pre-eclampsia-Like Impairments in Rats Through the NLRP3 Inflammasome.","authors":"Shuangyan Yang,&nbsp;Junfeng Zhang,&nbsp;Dan Chen,&nbsp;Jie Ding,&nbsp;Yanhong Zhang,&nbsp;Lili Song","doi":"10.1007/s40268-022-00402-6","DOIUrl":"https://doi.org/10.1007/s40268-022-00402-6","url":null,"abstract":"<p><strong>Background and objectives: </strong>Aspirin is a common drug for the treatment of pre-eclampsia. We aimed to explore whether quercetin as a supplement to aspirin could enhance the therapeutic outcome in pre-eclampsia rat models. We further aimed to evaluate the nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome as a potential pre-eclampsia-related molecular mechanism, which can be affected by quercetin treatment.</p><p><strong>Methods: </strong>Rat pre-eclampsia models were established using an intravenous lipopolysaccharide injection after gestation. Rats were treated with aspirin and quercetin at 6-18 days after pregnancy. On day 20, blood, fetus, and placenta were harvested. Blood pressure and the level of proteinuria were measured every 4 days. Fetal outcomes were analyzed by pup body weight. Serum soluble Fms-like tyrosine kinase-1, PIGF, interleukin-6, and interleukin-10 levels were measured using the enzyme-linked immunosorbent assay. Caspase-1, NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain, and p-caspase-1 levels in the placenta were assessed using western blot or quantitative real-time polymerase chain reaction analyses.</p><p><strong>Results: </strong>Pre-eclampsia rat models showed a pronounced increase in systolic blood pressure and proteinuria after 4 days of pregnancy, while aspirin, quercetin, and aspirin/quercetin combinatory treatment significantly attenuated the blood pressure and proteinuria abnormalities. Notably, the aspirin/quercetin combinatory treatment showed the highest efficacy in attenuating pre-eclampsia-like symptoms. Placental caspase-1 and NLRP3 levels also showed the greatest attenuation in pre-eclampsia rats after aspirin/quercetin treatment.</p><p><strong>Conclusions: </strong>Our data suggested that quercetin supplementation to aspirin is more effective in attenuating symptoms of pre-eclampsia and improving pregnancy outcomes compared with quercetin or aspirin alone. Quercetin can ameliorate placental NLRP3 inflammasome activation, which might serve as an underlying mechanism for its therapeutic efficacies in pre-eclampsia.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":"22 4","pages":"271-279"},"PeriodicalIF":3.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/56/7a/40268_2022_Article_402.PMC9700538.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33470815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Validation of the Covariates Pharmacokinetic Model for Propofol in an Adult Population.","authors":"Christopher Hawthorne,&nbsp;Martin Shaw,&nbsp;Ruaraidh Campbell,&nbsp;Nicholas Sutcliffe,&nbsp;Shiona McKelvie,&nbsp;Stefan Schraag","doi":"10.1007/s40268-022-00404-4","DOIUrl":"https://doi.org/10.1007/s40268-022-00404-4","url":null,"abstract":"<p><strong>Background and objective: </strong>Pharmacokinetic or pharmacokinetic-pharmacodynamic models have been instrumental in facilitating the clinical use of propofol in target-controlled infusion systems in anaesthetic practice. There has been debate over which model should be recommended for practice. The covariates model is an updated pharmacokinetic model for propofol. The aim of this study was to prospectively validate this model in an adult population.</p><p><strong>Methods: </strong>Twenty-nine patients were included, with a range of ages to assess model performance in younger and older individuals. Subjects received propofol through a target-controlled infusion device programmed with the covariates model. Subjects were randomised to one of two increasing/decreasing regimes of propofol plasma target concentrations between 2 and 5 μg.mL^-1. After the start of the infusion, arterial and venous blood samples were drawn at pre-specified timepoints between 1.5 and 20 min and between 1.5 and 45 min, respectively. Predictive performance was assessed using established methodology.</p><p><strong>Results: </strong>The model achieved a bias of 9 (- 45 to 82) and precision of 24 (9-82) for arterial samples and bias of - 8 (- 64 to 70) and precision of 23 (9-70) for venous samples. Predicted concentrations tended to be higher than the measured concentrations in female individuals but lower in male individuals. There was no clear systematic difference in the bias between younger and older patients.</p><p><strong>Conclusions: </strong>The covariates propofol pharmacokinetic model achieved an acceptable level of predictive performance, as assessed by both arterial and venous sampling, for use in target-controlled infusion in clinical practice.</p><p><strong>Clinical trial registration: </strong>NCT01492712 (15 December, 2011).</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":"22 4","pages":"289-300"},"PeriodicalIF":3.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/26/4e/40268_2022_Article_404.PMC9700536.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33494376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acknowledgement to Referees","authors":"Not Available Not Available","doi":"10.1007/s40268-022-00409-z","DOIUrl":"https://doi.org/10.1007/s40268-022-00409-z","url":null,"abstract":"","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":"22 1","pages":"255 - 256"},"PeriodicalIF":3.0,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43497698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of the US Safety Data for Edaravone (Radicava^®) From the Third Year After Launch.","authors":"Angela Genge,&nbsp;Benjamin Rix Brooks,&nbsp;Björn Oskarsson,&nbsp;Alexander Kalin,&nbsp;Ming Ji,&nbsp;Stephen Apple,&nbsp;Laura Bower","doi":"10.1007/s40268-022-00391-6","DOIUrl":"https://doi.org/10.1007/s40268-022-00391-6","url":null,"abstract":"<p><strong>Background: </strong>Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neuromuscular disease with no curative therapies. Edaravone (Radicava^®) (Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan), approved in the United States (US) for ALS in adults in 2017, was shown in a clinical trial to slow the rate of physical functional decline in ALS and is administered intravenously. The aim of this paper is to summarize the observed safety profile from real-world patient use during the first 3 years of edaravone availability in the US.</p><p><strong>Methods: </strong>Edaravone usage data were collected, and adverse events (AEs) were identified from a postmarketing safety database from August 8, 2017 through August 7, 2020 (cutoff date).</p><p><strong>Results: </strong>As of October 3, 2020, 5207 ALS patients had been treated with edaravone. As of August 7, 2020, the most commonly reported AEs included death (not specified), drug ineffective, disease progression, therapeutic response unexpected, fall, asthenia, fatigue, muscular weakness, gait disturbance, and dyspnea. The most commonly reported serious AEs (SAEs) included death (not specified), pneumonia, disease progression, ALS, fall, dyspnea, respiratory failure, device-related infection, hospitalization, and injection-site infection. There were 687 deaths, with 494 reported as death without specifying the cause. Deaths were most commonly attributed to ALS, disease progression, respiratory failure, or pneumonia. Review for administration-site reactions revealed 95 AEs, including 34 site infections, with 22 SAEs (all non-fatal). Five non-fatal SAEs of anaphylaxis were reported.</p><p><strong>Conclusion: </strong>In the postmarketing reporting to date, no new safety signals were identified beyond those already known from the edaravone clinical trial program.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":"22 3","pages":"205-211"},"PeriodicalIF":3.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c0/8f/40268_2022_Article_391.PMC9433633.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40070552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study of the Stability of Sandoz Rituximab Biosimilar Rixathon^®/Riximyo^® When Subjected for up to 21 Days to Ambient Storage.","authors":"Roman Borišek,&nbsp;André Mischo,&nbsp;Ida Šmid","doi":"10.1007/s40268-022-00393-4","DOIUrl":"https://doi.org/10.1007/s40268-022-00393-4","url":null,"abstract":"<p><strong>Aim: </strong>The purpose of this study was to evaluate the extended physicochemical and biological stability of Sandoz Rixathon®/Riximyo® (SDZ-RTX) after exposure to out-of-fridge (OOF) conditions.</p><p><strong>Materials and methods: </strong>The impact of the short-term temperature excursion on stability parameters of SDZ-RTX was simulated by subsequently exposing the three batches of SDZ-RTX (100 and 500 mg) to OOF conditions, (I) 25 ± 2 °C/60 ± 5% relative humidity (RH) and (II) 30 ± 2 °C/65 ± 5% RH, for up to 21 days after more than the claimed 36-month shelf-life storage in long-term conditions (5 ± 3 °C). Analytical methods used included the cation exchange chromatography (CEX), size exclusion chromatography (SEC), and non-reducing capillary electrophoresis-sodium dodecyl sulfate (nrCE-SDS), as well as biological activity by complement-dependent cytotoxicity (CDC)-bioactivity as well as further methods, for example, related to identity and pharmacopoeia test methods.</p><p><strong>Results: </strong>No notable changes were observed across all batches with respect to identity (charge and primary structure), pharmaceutical tests (clarity, visible and subvisible particles analytics, container appearance, degree of coloration, pH, osmolality, extractable volume, and container closure integrity testing), protein content by UV and microbiological parameters (sterility and bacterial endotoxins) under both OOF conditions. Only minor changes were observed for parameters evaluated via SEC, CEX, and nrCE-SDS. For potency (CDC-bioactivity) only one of the batches showed a relevant change. Even for these stability-indicating test methods, all analyzed parameters complied with the shelf-life specifications.</p><p><strong>Conclusion: </strong>SDZ-RTX is safe for use even under worst-case conditions, for example, after subjecting it for up to 21 days at OOF conditions (25 ± 2 °C/60 ± 5% RH or 30 ± 2 °C/65 ± 5% RH) after the batches had reached an age that was already beyond the claimed shelf-life.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":"22 3","pages":"225-234"},"PeriodicalIF":3.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/af/60/40268_2022_Article_393.PMC9433506.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40686131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness and Safety of Upadacitinib in the Treatment of Moderate-Severe Atopic Dermatitis: A Multicentric, Prospective, Real-World, Cohort Study.","authors":"Andrea Chiricozzi,&nbsp;Niccolò Gori,&nbsp;Alessandra Narcisi,&nbsp;Anna Balato,&nbsp;Alessio Gambardella,&nbsp;Michela Ortoncelli,&nbsp;Angelo Valerio Marzano,&nbsp;Riccardo Balestri,&nbsp;Giovanni Palazzo,&nbsp;Michele Pellegrino,&nbsp;Marco Romanelli,&nbsp;Giovanni Tripepi,&nbsp;Ketty Peris,&nbsp;Antonio Costanzo","doi":"10.1007/s40268-022-00396-1","DOIUrl":"https://doi.org/10.1007/s40268-022-00396-1","url":null,"abstract":"<p><strong>Background: </strong>The efficacy and safety of upadacitinib in atopic dermatitis (AD) have been defined in clinical trials, but no real-world data are currently available. We aimed to assess the safety and effectiveness of upadacitinib in a real-world AD patient cohort that mostly included patients who failed the available systemic therapies, including dupilumab.</p><p><strong>Methods: </strong>Prospective cohort study collecting data on upadacitinib-treated AD adult patients completing at least 16 weeks of therapy.</p><p><strong>Results: </strong>Forty-three patients showed rapid and marked response to upadacitinib with significant reduction of all disease severity scores since the first follow-up visit. At week 16, Eczema Area and Severity Index (EASI) 75, EASI 90, and EASI 100 response was observed in 97.5%, 82.1%, and 69.2% of patients, respectively. EASI 90 response reflected the achievement of a clear or almost clear condition (POEM 0-2), self-evaluated by 79.5% of patients. Patients' quality of life improved as suggested by the achievement of DLQI 0/1 by 38.5% of patients at week 4, and by 76.9% at week 16.</p><p><strong>Conclusion: </strong>Elevated effectiveness and favorable safety of upadacitinib were confirmed in patients unresponsive to dupilumab, who were not included in upadacitinib trials.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":"22 3","pages":"245-252"},"PeriodicalIF":3.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a5/e9/40268_2022_Article_396.PMC9362214.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40598046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiplatelets Versus Anticoagulation in Cervical Artery Dissection: A Systematic Review and Meta-analysis of 2064 Patients.","authors":"Abdulrahman Ibrahim Hagrass, Bashar Khaled Almaghary, Mohamed Abdelhady Mostafa, Mohamed Elfil, Sarah Makram Elsayed, Amira A Aboali, Aboalmagd Hamdallah, Mohammed Tarek Hasan, Mohammed Al-Kafarna, Khaled Mohamed Ragab, Mohamed Fahmy Doheim","doi":"10.1007/s40268-022-00398-z","DOIUrl":"10.1007/s40268-022-00398-z","url":null,"abstract":"<p><strong>Background and objectives: </strong>In young people aged < 50 years, cervical artery dissection (CeAD) is among the most common causes of stroke. Currently, there is no consensus regarding the safest and most effective antithrombotic treatment for CeAD. We aimed to synthesize concrete evidence from studies that compared the efficacy and safety of antiplatelet (AP) versus anticoagulant (AC) therapies for CeAD.</p><p><strong>Methods: </strong>We searched major electronic databases/search engines from inception till September 2021. Cohort studies and randomized controlled trials (RCTs) comparing anticoagulants with antiplatelets for CeAD were included. A meta-analysis was conducted using articles that were obtained and found to be relevant. Mean difference (MD) with 95% confidence interval (CI) was used for continuous data and odds ratio (OR) with 95% CI for dichotomous data.</p><p><strong>Results: </strong>Our analysis included 15 studies involving 2064 patients, 909 (44%) of whom received antiplatelets and 1155 (56%) received anticoagulants. Our analysis showed a non-significant difference in terms of the 3-month mortality (OR 0.47, 95% CI 0.03-7.58), > 3-month mortality (OR 1.63, 95% CI 0.40-6.56), recurrent stroke (OR 0.97, 95% CI 0.46-2.02), recurrent transient ischaemic attack (TIA) (OR 0.93, 95% CI 0.44-1.98), symptomatic intracranial haemorrhage (sICH) (OR 0.38, 95% CI 0.12-1.19), and complete recanalization (OR 0.70, 95% CI 0.46-1.06). Regarding primary ischaemic stroke, the results favoured AC over AP among RCTs (OR 6.97, 95% CI 1.25-38.83).</p><p><strong>Conclusion: </strong>Our study did not show a considerable difference between the two groups, as all outcomes showed non-significant differences between them, except for primary ischaemic stroke (RCTs) and complete recanalization (observational studies), which showed a significant favour of AC over AP. Even though primary ischaemic stroke is an important outcome, several crucial points that could affect these results should be paid attention to. These include the incomplete adjustment for the confounding effect of AP-AC doses, frequencies, administration compliance, and others. We recommend more well-designed studies to assess if unnecessary anticoagulation can be avoided in CeAD.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":"22 3","pages":"187-203"},"PeriodicalIF":2.2,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e3/82/40268_2022_Article_398.PMC9433613.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40598047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}