Monitoring adverse events of low-dose glucocorticoid therapy: EULAR recommendations for clinical trials and daily practice

ObjectiveTo develop recommendations on monitoring for adverse events (AEs) of low-dose glucocorticoid (GC) therapy (≤7.5 mg prednisone or equivalent daily) in clinical trials and daily practice.MethodsLiterature was searched for articles containing information on incidence and monitoring of GC-related AEs using PubMed, EMBASE and Cochrane databases. Second, the authors searched for broad accepted guidelines on the monitoring of certain AEs (eg, WHO guidelines on screening for diabetes). Available data were summarised and discussed among experts (rheumatologists and patients) of the EULAR Task Force to decide which potential AEs should be monitored, how and at which interval.ResultsData on monitoring proved to be scarce; most articles were focused on therapeutic effects of GCs, not on occurrence and monitoring of AEs. Most recommendations had to be based on consensus. Those for clinical trials aimed at getting insights into incidence, prevalence and clinical relevance of AEs to create a comprehensive and valid AE-profile of GC therapy. The set of AEs to monitor is therefore more extensive, and often consists of assessments at baseline and at end of trials. Recommendations for daily practice are meant to protect patients from real dangers, which can be prevented or treated. Standard care monitoring needs NOT be extended for patients on low-dose GC therapy, except for osteoporosis (follow national guidelines), and baseline assessments of ankle edema, fasting blood glucose and risk factors for glaucoma.ConclusionGiven the incompleteness of literature data, consensus-based recommendations on monitoring for GC-related AEs were created, separately for daily practice and clinical trials.

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EULAR* has made recommendations for the monitoring of adverse events of low-dose glucocorticoid therapy in both clinical trials and daily practice.

Reactions Weekly ◽

10.2165/00128415-201013200-00008 ◽

2010 ◽

Vol &NA; (1320) ◽

pp. 3

Author(s):

&NA;

Keyword(s):

Clinical Trials ◽

Adverse Events ◽

Low Dose ◽

Daily Practice ◽

Glucocorticoid Therapy

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Recombinant Human Adenovirus-p53 Therapy for the Treatment of Oral Leukoplakia and Oral Squamous Cell Carcinoma: A Systematic Review

Medicina ◽

10.3390/medicina57050438 ◽

2021 ◽

Vol 57 (5) ◽

pp. 438

Author(s):

Jagadish Hosmani ◽

Shazia Mushtaq ◽

Shahabe Saquib Abullais ◽

Hussain Mohammed Almubarak ◽

Khalil Assiri ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Oral Cancer ◽

Adverse Events ◽

Randomized Clinical Trials ◽

Oral Leukoplakia ◽

Research Articles ◽

Original Research ◽

Therapeutic Effects ◽

The World

Background and Objectives: Oral cancer is the 6th most common cancer in the world and oral leukoplakia is an oral potentially malignant disorder that could develop into oral cancer. This systematic review focusses on randomized clinical trials for recombinant adenovirus p-53 (rAD-p53) therapy for the treatment of oral leukoplakia and cancer. Materials and Methods: We searched for research articles on various databases such as Pubmed/Medline, Embase, CNKI (China National Knowledge Infra-structure), Springerlink, cochrane and Web of sciences from 2003 to 2020. MeSH (Medical Subject Headings) terms were used for the search. Inclusion criteria included original research, randomized clinical trials and articles only in English language. Exclusion criteria were any articles that were not research articles, not randomized trials, non-human studies, etc. The articles were further graded on the Jadad scale. Results: 578 articles were assessed from various databases; only 3 articles were found to be appropriate for this review. Thus, meta-analysis was not performed because of heterogeneity and lack of data. In the three studies, whether rAD-p53 was used as a standalone therapy or with other therapies, there was a beneficial effect of the therapy. Furthermore, there were no serious adverse events and the only adverse events reported were fever, pain at the local injection site, flu-like symptoms and lowered WBC count. Conclusions: Thus, we can conclude that this therapy has a potential for beneficial therapeutic effects and further clinical trials with more patients need to be performed to get better understanding of the effect of rAD-p53 therapy, which probably will pave the way to its approval in other parts of the world.

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Clinical Adverse Events of High-Dose vs Low-Dose Sodium–Glucose Cotransporter 2 Inhibitors in Type 2 Diabetes: A Meta-Analysis of 51 Randomized Clinical Trials

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa586 ◽

2020 ◽

Vol 105 (11) ◽

Cited By ~ 1

Author(s):

Fang-Hong Shi ◽

Hao Li ◽

Jiang Yue ◽

Yi-Hong Jiang ◽

Zhi-Chun Gu ◽

...

Keyword(s):

Type 2 Diabetes ◽

Clinical Trials ◽

Adverse Events ◽

Low Dose ◽

Randomized Clinical Trials ◽

Sglt2 Inhibitors ◽

High Dose ◽

Sodium Glucose Cotransporter ◽

Subgroup Analyses

Abstract Aims The aims of this work are to assess the clinical adverse events (AEs) of high-dose vs low-dose sodium–glucose cotransporter 2 inhibitors (SGLT2 inhibitors) in patients with type 2 diabetes mellitus (T2DM). Methods We searched MEDLINE, EMBASE, and Cochrane Library from January 1, 2006 to March 10, 2020, for identifying eligible randomized clinical trials (RCTs) that reported AEs by high-dose and low-dose SGLT2 inhibitors in T2DM patients. Random-effects models was used to obtain summary relative risks (RRs) with associated 95% CIs. Prespecified subgroup analyses according to individual SGLT2 inhibitors and follow-up duration, and leave-one-out sensitivity analysis were conducted. Results A total of 51 RCTs involving 24 371 patients (12 208 received high-dose and 12 163 received low-dose SGLT2 inhibitors) were included. Overall, the heterogeneity among included studies was relatively low (I2 < 50% for each outcome). No significant differences between high-dose and low-dose SGLT2 inhibitors were observed for overall safety (including any AEs, serious AEs, AEs leading to discontinuation, and death) and specified safety (including infections and infestations, musculoskeletal disorders, gastrointestinal disorders, osmotic diuresis-related AEs, volume-related AEs, renal-related AEs, and metabolism and nutrition), except for a mild increase in risk for AEs related to study drugs (RR: 1.08; 95% CI, 1.01-1.16) that mainly derived from canagliflozin (RR: 1.17; 95% CI, 1.05-1.30). Subgroup analyses were consistent with the primary outcomes. Conclusions This study provided substantial evidence that AEs of SGLT2 inhibitors were not dose related.

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Effect of Treatment with Colchicine After Acute Coronary Syndrome on Major Cardiovascular Events: A Meta-Analysis of Clinical Trials

10.21203/rs.3.rs-908934/v1 ◽

2021 ◽

Author(s):

Erfan Razavi ◽

Akam Ramezani ◽

Asma Kazemi ◽

Armin Attar

Keyword(s):

Clinical Trials ◽

Acute Coronary Syndrome ◽

Adverse Events ◽

Large Scale ◽

Low Dose ◽

Meta Analysis ◽

Coronary Syndrome ◽

Hs Crp ◽

The Impact

Abstract Purpose Colchicine as an anti-inflammatory drug might be effective in the treatment of atherosclerosis, an inflammatory-based condition. The aim of this systematic review and meta-analysis was to evaluate the impact of colchicine on acute coronary syndrome (ACS). Methods We searched SCOPUS, PubMed, and Web of Science up to September 27, 2020. All clinical trials which evaluated the effect of colchicine on ACS patients and reported high-sensitivity C-reactive protein (hs-CRP) serum level or gastrointestinal (GI) adverse events with at least 5-day follow up or death, Myocardial infarction (MI), and stroke with at least 30-day follow up as outcomes were included. Results Finally, seven publications were analyzed. The results of our study revealed that colchicine has a marginally significant effect on hs-CRP attenuation. Furthermore, colchicine manifested promising results by declining the risk of stroke by 70%. However, MI and primary composite endpoint did not differ between the colchicine and non-colchicine group. Although colchicine did not significantly increase GI adverse events in the pooled analysis, the dose-dependent effect was detected. Low dose consumption can avoid GI side effects of colchicine. Conclusion Colchicine has shown some molecular and clinical promising results in ACS patients. The lack of effect of colchicine on MI and all-cause mortality can be partly attributed to the limitations of previous studies. Since colchicine is an inexpensive and easy-to-access drug that has shown to be safe in low-dose regimens in the clinical setting, it worth that future large-scale well-designed studies address this issue by resolving the limitations of previous research.

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Ongoing randomized clinical trials for the treatment of thrombosis in the antiphospholipid syndrome

Hämostaseologie ◽

10.1055/s-0037-1619507 ◽

2001 ◽

Vol 21 (02) ◽

pp. 77-81 ◽

Cited By ~ 2

Author(s):

G. Finazzi

Keyword(s):

Clinical Trials ◽

Large Scale ◽

Low Dose ◽

Randomized Clinical Trials ◽

Oral Anticoagulants ◽

Collaborative Study ◽

Clinical Problem ◽

Vascular Events ◽

Dose Oral ◽

Adverse Pregnancy

SummaryThrombotic events are a major clinical problem for patients with antiphospholipid antibodies (APA). However, current recommendations for their prevention and treatment are still based on retrospective studies. Data from large scale, prospective clinical trials are required to ultimately identify the optimal management of these patients. To date, at least four randomized studies are underway. The WAPS and PAPRE clinical trials are aimed to establish the correct duration and intensity of oral anticoagulation in APA patients with major arterial or venous thrombosis. The WARSS-APASS is a collaborative study to evaluate the efficacy and safety of aspirin or low-dose oral anticoagulants in preventing the recurrence of ischemic stroke. The recently announced UK Trial compares low-dose aspirin with or without low-intensity anticoagulation for the primary prevention of vascular events in APA-positive patients with SLE or adverse pregnancy history, but still thrombosis-free. It is hoped that the results of these trials will be available soon since clinicians urgently need more powerful data to treat their patients with the APA syndrome.

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POOLED ANALYSIS OF ADVERSE EVENTS AND TOLERABILITY DATA FROM TWO PIVOTAL PHASE 2/3 CLINICAL TRIALS OF THE NEW SCIG 20% FORMULATION IN PATIENTS WITH PID

10.26226/morressier.594a7d48d462b8028d8938f4 ◽

2017 ◽

Author(s):

Kim Haines

Keyword(s):

Clinical Trials ◽

Adverse Events ◽

Pooled Analysis ◽

Phase 2 ◽

Pivotal Phase ◽

Tolerability Data

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The Novel Antipsychotic Drug Cariprazine and Cognition Enhancing Drugs: Indications for Their Use as an Add-on Therapy in Schizophrenia

Current Pharmaceutical Design ◽

10.2174/1381612826666201210123229 ◽

2020 ◽

Vol 26 ◽

Author(s):

Felix-Martin Werner ◽

Rafael Coveñas

Keyword(s):

Clinical Trials ◽

Maintenance Therapy ◽

Antipsychotic Drug ◽

Cognitive Functions ◽

Antipsychotic Drugs ◽

Psychotic Disorders ◽

Therapeutic Effects ◽

Treatment Resistant ◽

Long Acting ◽

Novel Antipsychotic

Background: Schizophrenia and schizoaffective disorder are treated with antipsychotic drugs. Some patients show treatment-resistant forms of psychotic disorders and, in this case, they can be treated with clozapine. In these patients and based on previous reviews on novel antipsychotic drugs, it is important to know whether an add-on therapy with new drugs can ameliorate the positive and negative schizophrenic scale (PANSS) total score. Objective: The aim of this review is to suggest an appropriate treatment for patients with treatment-resistant forms of psychotic disorders. A combination of current available antipsychotic drugs with novel antipsychotic or modulating drugs might improve negative schizophrenic symptoms and cognitive function and thereby social functioning and quality of life. Results: The mechanisms of action, the therapeutic effects and the pharmacokinetic profiles of novel antipsychotic drugs such as cariprazine, brexipiprazole and lumateperone are up-dated. Published case reports of patients with treatmentresistant psychoses are also discussed. These patients were treated with clozapine but a high PANSS total score was observed. Only an add-on therapy with cariprazine improved the score and, above all, negative schizophrenic symptoms and cognitive functions. To ensure a constant antipsychotic drug concentration, long-acting injectable antipsychotic drugs may be a choice for a maintenance therapy in schizophrenia. New modulating drugs, such as receptor positive allosteric modulators (N-methyl-D-aspartate receptor; subtype 5 of the metabotropic glutamatergic receptor) and encenicline, an alpha7 nicotinic cholinergic receptor agonist, are being investigated in preclinical and clinical trials. Conclusion: In clinical trials, patients with treatment-resistant forms of psychosis should be examined to know whether a combination therapy with clozapine and a novel antipsychotic drug can ameliorate the PANSS total score. In schizophrenia, long-acting injectable antipsychotic drugs are a safe and tolerable maintenance therapy. In further clinical studies, it should be investigated whether patients with treatment-resistant forms of psychoses can improve negative schizophrenic symptoms and cognitive functions by an add-on therapy with cognition enhancing drugs.

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Crizotinib Versus Chemotherapy on ALK-positive NSCLC: A Systematic Review of Efficacy and Safety

Current Cancer Drug Targets ◽

10.2174/1568009617666170623115846 ◽

2018 ◽

Vol 19 (1) ◽

pp. 41-49 ◽

Cited By ~ 2

Author(s):

Mingxia Wang ◽

Guanqi Wang ◽

Haiyan Ma ◽

Baoen Shan

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Adverse Events ◽

Objective Response Rate ◽

Retrospective Studies ◽

Response Rate ◽

Objective Response ◽

Treated Group ◽

Efficacy And Safety ◽

Alk Positive

Introduction: Crizotinib was approved to treat anaplastic lymphoma kinase (ALK)- positive non-small cell lung cancer (NSCLC) by the Food and Drug Administration in 2011.We conducted a systematic review of clinical trials and retrospective studies to compare the efficacy and safety of crizotinib with chemotherapy. </P><P> Methods: We searched electronic databases from inception to Dec. 2016. Clinical trials and retrospective studies regarding crizotinib and crizotinib versus chemotherapy in treatment of NSCLC were eligible. The primary outcomes were the objective response rate (ORR) and disease control rate (DCR). Results: Nine studies (five clinical trials and four retrospective studies) including 729 patients met the inclusion criteria. Crizotinib treatment revealed 1-year OS of 77.1% and PFS of 9.17 months. And crizotinib had a better performance than chemotherapy in ORR (OR: 4.97, 95%CI: 3.16 to 7.83, P<0.00001, I2=35%). DCR revealed superiority with crizotinib than chemotherapy (OR: 3.42, 95% CI: 2.33 to 5.01, P<0.00001, I2=0%). PR (partial response) were significant superior to that of chemotherapy through direct systematic review. No statistically significant difference in CR (complete response) was found between crizotinib-treated group and chemotherapy-treated group. Regarding SD (stable disease), chemotherapy-treated group had a better performance than crizotinib-treated group. Common adverse events associated with crizotinib were visual disorder, gastrointestinal side effects, and elevated liver aminotransferase levels, whereas common adverse events with chemotherapy were fatigue, nausea, and hematologic toxicity. This systematic review revealed improved objective response rate and increased disease control rate in crizotinib group comparing with chemotherapy group. Crizotinib treatment would be a favorable treatment option for patients with ALK-positive NSCLC. ALK inhibitors may have future potential applications in other cancers driven by ALK or c-MET gene mutations.

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