scholarly journals Effectiveness and Safety of Abrocitinib in Patients with Moderate-to-Severe Atopic Dermatitis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Hammad Ali Fadlalmola ◽  
Muayad Saud Albadrani ◽  
Amal Mohamed Elhusein ◽  
Wahieba E. Mohamedsalih ◽  
Veerabhadra D. S. Swamy ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Janus Kinase ◽  
Severe Atopic Dermatitis ◽  
Upper Respiratory Tract ◽  
Serious Adverse Events ◽  
Inverse Variance ◽  
Iga Response

Background. Atopic dermatitis (AD) is a complex, chronic, inflammatory skin disease characterized by pruritic, intense itching, and eczematous lesions affecting about 25% of children and 2% to 3% of adults worldwide. Abrocitinib is a selective inhibitor of Janus kinase-1 (JAK1) enzyme inhibiting the inflammatory process. Therefore, we aimed to assess the efficacy and safety of abrocitinib for moderate-to-severe AD. Methods. We systematically searched PubMed, Cochrane, Web of Science, Scopus, and EczemATrials till Feb 1, 2021, for reliable trials. The analysis was conducted using an inverse-variance method. The results were pooled as mean difference/event rate and 95% confidence interval. Results. Abrocitinib 100 mg and 200 mg were associated with higher IGA response, EASI-50% responders, EASI-75% responders, EASI-90% responders, number of participants with at least 4-point improvements in NRS, and quality of life measured by DLQI and CDLQI than placebo. Also, 100 mg and 200 mg were associated with lower SCORAD index, %BSA, PSAAD index, and POEM index than placebo. Abrocitinib 100 mg and 200 mg were not associated with adverse events such as upper respiratory tract infection, nasopharyngitis, dermatitis, atopic, any serious adverse events, and death. Conclusion. Abrocitinib in dose 100 mg or 200 mg is an effective, well-tolerated, and promising drug in treating patients with moderate-to-severe atopic dermatitis. However, the analysis favored the efficacy of abrocitinib 200 mg over 100 mg, but side effects such as nausea and headache are likely to occur more with 200 mg.

scholarly journals Efficacy and Safety of Janus Kinase Inhibitors for the Treatment of Atopic Dermatitis: A Systematic Review and Meta-Analysis

Dermatology ◽  
2021 ◽  
pp. 1-11
Author(s):  
Chenyang Li ◽  
Xun Sun ◽  
Kun Zhao ◽  
Fanxiang Meng ◽  
Lin Li ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Randomized Clinical Trials ◽  
Kinase Inhibitors ◽  
Weighted Mean Difference ◽  
Meta Analysis ◽  
Janus Kinase ◽  
Primary Study ◽  
Efficacy And Safety ◽  
Jak Inhibitors ◽  
Iga Response

<b><i>Background:</i></b> Current therapeutic options for atopic dermatitis (AD) are limited. Janus kinase (JAK) inhibitors may be viable alternatives. <b><i>Objectives:</i></b> To assess the efficacy and safety of JAK inhibitors for AD treatment. <b><i>Methods:</i></b> We searched PubMed, Embase, the Cochrane Controlled Register of Trials, Web of Science, Global Resource of Eczema Trials database, and ClinicalTrials.gov from inception to September 1, 2020. Randomized clinical trials (RCTs) comparing JAK inhibitors with placebo/vehicle treatment for AD patients were included. The primary study outcomes included (1) the change (%) from the Eczema Area and Severity Index (EASI) baseline expressed as weighted mean difference (WMD) and 95% confidence interval (95% CI), and (2) the Investigator’s Global Assessment (IGA) response and safety outcomes expressed as relative risk (RR) and 95% CI. <b><i>Results:</i></b> We included 14 RCTs published in 13 studies (3,822 patients). Treatment with JAK inhibitors significantly improved IGA response (RR 2.83, 95% CI 2.25–3.56, <i>p</i> &#x3c; 0.001) and EASI score (WMD –28.82, 95% CI –34.48 to −23.16, <i>p</i> &#x3c; 0.001). JAK inhibitor treatment achieved the largest improvement in both IGA response (RR 3.59, 95% CI 2.66–4.84, <i>p</i> &#x3c; 0.001) and EASI score (WMD –42.00, 95% CI –48.64 to −35.36, <i>p</i> &#x3c; 0.001) by week 4 of treatment. Topical JAK inhibitors were significantly more efficacious than oral inhibitors. Upadacitinib treatment for 4 weeks was most effective in reducing EASI score (WMD –53.92, 95% CI –69.26 to −38.58, <i>p</i> &#x3c; 0.001), while abrocitinib for 4 weeks led to the most effective IGA response (RR 5.47, 95% CI 2.74–10.93, <i>p</i> &#x3c; 0.001). There was no difference in the frequency of adverse events (AEs) leading to discontinuation; however, JAK inhibitors use, especially abrocitinib, led to a higher incidence of treatment-emergent AEs (RR 1.25, 95% CI 1.10–1.42, <i>p</i> = 0.001). <b><i>Conclusion:</i></b> Our results imply that JAK inhibitors are an effective and safe AD treatment. Nevertheless, further trials with longer duration and head-to-head comparisons of different JAK inhibitors are needed.

scholarly journals Long-acting muscarinic antagonists vs. long-acting β 2 agonists in COPD exacerbations: a systematic review and meta-analysis

2017 ◽  
Vol 43 (4) ◽  
pp. 302-312 ◽  
Author(s):  
Israel Silva Maia ◽  
Mariângela Pimentel Pincelli ◽  
Victor Figueiredo Leite ◽  
João Amadera ◽  
Anna Maria Buehler
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Therapeutic Effects ◽  
Muscarinic Antagonists ◽  
Serious Adverse Events ◽  
Exacerbation Rate ◽  
Copd Exacerbations ◽  
Long Acting

ABSTRACT Objective: To determine whether long-acting muscarinic antagonists (LAMAs) provide superior therapeutic effects over long-acting β2 agonists (LABAs) for preventing COPD exacerbations. Methods: This was a systematic review and meta-analysis of randomized clinical trials involving patients with stable, moderate to severe COPD according to the Global Initiative for Chronic Obstructive Lung Disease criteria, treated with a LAMA (i.e., tiotropium bromide, aclidinium, or glycopyrronium), followed for at least 12 weeks and compared with controls using a LABA in isolation or in combination with a corticosteroid. Results: A total of 2,622 studies were analyzed for possible inclusion on the basis of their title and abstract; 9 studies (17,120 participants) were included in the analysis. In comparison with LABAs, LAMAs led to a greater decrease in the exacerbation rate ratio (relative risk [RR] = 0.88; 95% CI: 0.84-0.93]; a lower proportion of patients who experienced at least one exacerbation (RR = 0.90; 95% CI: 0.87-0.94; p < 0.00001); a lower risk of exacerbation-related hospitalizations (RR = 0.78; 95% CI: 0.69-0.87; p < 0.0001); and a lower number of serious adverse events (RR = 0.81; 95% CI: 0.67-0.96; p = 0.0002). The overall quality of evidence was moderate for all outcomes. Conclusions: The major findings of this systematic review and meta-analysis were that LAMAs significantly reduced the exacerbation rate (exacerbation episodes/year), as well as the number of exacerbation episodes, of hospitalizations, and of serious adverse events.

scholarly journals Systematic Review on the Efficacy and Safety of Oral Janus Kinase Inhibitors for the Treatment of Atopic Dermatitis

2021 ◽  
Vol 8 ◽  
Author(s):  
Michelle Le ◽  
Melissa Berman-Rosa ◽  
Feras M. Ghazawi ◽  
Marc Bourcier ◽  
Loretta Fiorillo ◽  
...  
Keyword(s):  
Systematic Review ◽  
Atopic Dermatitis ◽  
Safety Profile ◽  
Kinase Inhibitors ◽  
Meta Analysis ◽  
Symptom Control ◽  
Janus Kinase ◽  
Severe Atopic Dermatitis ◽  
Eligibility Criteria ◽  
Janus Kinase Inhibitors

Background: Atopic dermatitis is a chronic, relapsing and remitting disease that can be difficult to treat despite a recently approved biologic therapy targeting IL-4/IL-13 receptor. Oral janus kinase inhibitors (JAKi) represent a novel therapeutic class of targeted therapy to treat moderate-to-severe atopic dermatitis (AD).Objective: To review the efficacy, safety, and pharmacokinetic characteristics of oral JAKi in the treatment of AD.Methods: A PRISMA systematic review was conducted using MEDLINE, EMBASE (Ovid), and PubMed databases for studies assessing the efficacy, safety, and/or pharmacokinetic properties of oral forms of JAKi in the treatment of AD in pediatric or adult populations from inception to June 2021.Results: 496 papers were reviewed. Of 28 articles that underwent full text screening, 11 met our inclusion criteria for final qualitative review. Four studies examined abrocitinib; three studies examined baricitinib; three examined upadacitinib and one examined gusacitinib (ASN002). Significant clinical efficacy and a reassuring safety profile was reported for all JAKi agents reviewed. Rapid symptom control was reported for abrocitinib, baricitinib and upadacitinib.Limitations: Given the relatively limited evidence for each JAKi and the differences in patient eligibility criteria between studies, the data was not deemed suitable for a meta-analysis at this time.Conclusion: Given their ability to achieve rapid symptom control with a reassuring safety profile, we recommend considering the use of JAKi as a reliable systemic treatment option for adult patients with moderate-to-severe AD, who are unresponsive to topical or skin directed treatments.

Adverse events of Dupilumab in adults with moderate-to-severe atopic dermatitis: A meta-analysis

2018 ◽  
Vol 54 ◽  
pp. 303-310 ◽  
Author(s):  
Zuzhen Ou ◽  
Chao Chen ◽  
Aijun Chen ◽  
Yao Yang ◽  
Weikang Zhou
Keyword(s):  
Atopic Dermatitis ◽  
Adverse Events ◽  
Meta Analysis ◽  
Severe Atopic Dermatitis

scholarly journals Efficacy and Safety of Hydroxychloroquine for Hospitalized COVID-19 Patients: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 10 (11) ◽  
pp. 2503
Author(s):  
Adrian V. Hernandez ◽  
Mi T. Phan ◽  
Jonathon Rocco ◽  
Vinay Pasupuleti ◽  
Joshuan J. Barboza ◽  
...  
Keyword(s):  
Adverse Events ◽  
Meta Analysis ◽  
Efficacy And Safety ◽  
Serious Adverse Events ◽  
Non Invasive ◽  
Non Invasive Ventilation ◽  
Inverse Variance ◽  
Secondary Outcomes ◽  
Meta Analyses

We systematically reviewed the efficacy and safety of hydroxychloroquine as treatment for hospitalized COVID-19. Randomized controlled trials (RCTs) evaluating hydroxychloroquine as treatment for hospitalized COVID-19 patients were searched until 2nd of December 2020. Primary outcomes were all-cause mortality, need of mechanical ventilation, need of non-invasive ventilation, ICU admission and oxygen support at 14 and 30 days. Secondary outcomes were clinical recovery and worsening, discharge, radiological progression of pneumonia, virologic clearance, serious adverse events (SAE) and adverse events. Inverse variance random effects meta-analyses were performed. Thirteen RCTs (n=18,540) were included. Hydroxychloroquine total doses ranged between 2000 and 12,400 mg; treatment durations were from 5 to 16 days and follow up times between 5 and 30 days. Compared to controls, hydroxychloroquine non-significantly increased mortality at 14 days (RR 1.07, 95%CI 0.92–1.25) or 30 days (RR 1.08, 95%CI 1.00–1.16). Hydroxychloroquine did not affect other primary or secondary outcomes, except SAEs that were significantly higher than the control (RR 1.24, 95%CI 1.05–1.46). Eleven RCTs had high or some concerns of bias. Subgroup analyses were consistent with main analyses. Hydroxychloroquine was not efficacious for treating hospitalized COVID-19 patients and caused more severe adverse events. Hydroxychloroquine should not be recommended as treatment for hospitalized COVID-19 patients.

scholarly journals Erenumab safety and efficacy in migraine: a systematic review and meta-analysis of randomized clinical trials

2018 ◽  
Author(s):  
Changyu Zhu ◽  
Jianmei Guan ◽  
Hua Xiao ◽  
Weinan Luo ◽  
Rongsheng Tong
Keyword(s):  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Preventive Treatment ◽  
Pooled Analysis ◽  
Cochrane Library ◽  
Serious Adverse Events ◽  
Increased Risk ◽  
Specific Medication ◽  
Mean Differences

Abstract Background: Erenumab is a new medicine approved lately in the US for the preventive treatment of migraine in adults. We aimed to conduct a meta-analysis to evaluate the efficacy and safety of erenumab in patients with migraine. Methods: The electronic database composed of PubMed, Embase and Cochrane library was independently retrieved by two reviewers. Only randomized controlled trials (RCTs) that compared between placebo and erenumab were included in this analysis. mean differences (MDs) and Pooled risk ratios (RRs) as well as their corresponding 95% confidence intervals (CIs) were calculated for continuous and dichotomous data, respectively. Results: Total five RCTs representing 2928 patients were included. Pooled analysis showed significant reductions of the 50% reduction(RR 1.55; 95%CI,1.35 to 1.77; P < 0.00001; I²=49%). In addition, the mean monthly migraine days (MMMDs) from baseline in the erenumab group compared with placebo (MD -1.32, 95%CI, -1.73 to -0.91; P < 0.00001; I²=100%) and migraine-specific medication days (MSMDs) from baseline (MD -1.41; 95%CI, -1.80 to -1.02; P＜0.00001; I²=100%) were significantly increased for the erenumab group compared with placebo. Furthermore, there was significant reduction of MSMDs from baseline in 140mg erenumab group compared to 70mg (MD=0.55; 95%CI:0.54 to 0.66; Z =10.95; P<0.00001; I²=90% ). Finally, there were no significant differences between erenumab group and placebo of any adverse events and serious adverse events. Conclusion: Among patients with migraine, both 70mg and 140mg erenumab are associated with reduction of MMMDs, MSMDs from baseline and increased rate of 50% reduction without increased risk of any adverse events and serious adverse events.

scholarly journals The safety, tolerability and mortality reduction efficacy of remdesivir; based on randomized clinical trials, observational and case studies reported safety outcomes: an updated systematic review and meta-analysis

2021 ◽  
Vol 12 ◽  
pp. 204209862110425
Author(s):  
Chenchula Santenna ◽  
Kota Vidyasagar ◽  
Krishna Chaitanya Amarneni ◽  
Sai Nikhila Ghanta ◽  
Balakrishnan Sadasivam ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Antiviral Drug ◽  
Mortality Reduction ◽  
Serious Adverse Events ◽  
Significant Difference ◽  
Grade 3

Introduction: Remdesivir, an experimental antiviral drug has shown to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), both in vitro and in vivo. The present systematic review and meta-analysis were performed to quantify the safety and tolerability of remdesivir, based on safety outcome findings from randomized controlled trials, observational studies and case reports of remdesivir in coronavirus disease 2019 (COVID-19) patients. Methods: We have performed a systematic search in the PubMed, Google Scholar and Cochrane Library using specific keywords such as ‘COVID-19’ OR ‘SARS CoV-2’ AND ‘Remdesivir’. The study endpoints include total adverse events (AEs), serious adverse events (SAEs), grade 3 and grade 4 AEs, mortality and drug tolerability. Statistical analysis was carried out by using Revman 5.4 software. Results: Total 15 studies were included for systematic review, but only 5 randomized clinical trials (RCTs) ( n = 13,622) were included for meta-analysis. Visual inspection of the forest plots for remdesivir 10-day versus placebo and remdesivir 10-day versus 5-day groups revealed that there is a significant difference in SAEs [10-day remdesivir versus control (odds ratio [OR] = 0.55, 0.40–0.74) p = 0.0001; I2 = 0%; 10-day remdesivir versus 5-day remdesivir (OR = 0.56, 0.38–0.84) p = 0.005; I2 = 13%]. In grade 4 AEs, there is a significant difference in 10-day remdesivir versus control (OR = 0.32, 0.19–0.54) p = 0.0001; I2 = 0%, but not in comparison to 5-day remdesivir (OR = 0.95, 0.59–1.54) p = 0.85; I2 = 0%. But there is no significant difference in grade 3 AEs [remdesivir 10 day versus control (OR = 0.81, 0.59–1.11) p = 0.19; I2 = 0%; 10-day remdesivir versus 5-day remdesivir (OR = 1.24, 0.86–1.80) p = 0.25; I2 = 0%], in total AEs [remdesivir 10 day versus control (OR = 1.07, 0.66–1.75) p = 0.77; I2 = 79%; remdesivir 10 day versus 5 day (OR = 1.08, 0.70–1.68) p = 0.73; I2 = 54%)], in mortality [10-day remdesivir versus control (OR = 0.93, 0.80–1.08) p = 0.32; I2 = 0%; 10-day remdesivir versus 5-day remdesivir (OR = 1.39, 0.73–2.62) p = 0.32; I2 = 0%)] and tolerability [remdesivir 10 day versus control (OR = 1.05, 0.51–2.18) p = 0.89; I2 = 65%, 10-day remdesivir versus 5-day remdesivir (OR = 0.86, 0.18–4.01) p = 0.85; I2 = 78%]. Discussion & Conclusion: Ten-day remdesivir was a safe antiviral agent but not tolerable over control in the hospitalized COVID-19 patients with a need of administration cautiousness for grade 3 AEs. There was no added benefit of 10- or 5-day remdesivir in reducing mortality over placebo. To avoid SAEs, we suggest for prior monitoring of liver function tests (LFT), renal function tests (RFT), complete blood count (CBC) and serum electrolytes for those with preexisting hepatic and renal impairments and patients receiving concomitant hepatotoxic or nephrotoxic drugs. Furthermore, a number of RCTs of remdesivir in COVID-19 patients are suggested. Plain Language Summary Ten-day remdesivir is a safe antiviral drug with common adverse events in comparison to placebo. The rate of serious adverse events and grade 3 adverse events were significantly lower in 10-day remdesivir in comparison to placebo/5-day remdesivir. There was no significant difference in the rate of tolerability and mortality reduction in 10-day remdesivir over placebo/5-day remdesivir. There were no new safety signals reported in vulnerable populations, paediatric, pregnant and lactating women.

scholarly journals The safety of MSC therapy over the past 15 years: a meta-analysis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yang Wang ◽  
Hanxiao Yi ◽  
Yancheng Song
Keyword(s):  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Web Of Science ◽  
Meta Analysis ◽  
Pooled Analysis ◽  
High Quality ◽  
Serious Adverse Events ◽  
The Past ◽  
Clinical Investigations ◽  
Different Populations

Abstract Background Despite increasing clinical investigations emphasizing the safety of mesenchymal stem cell (MSC) therapy in different populations with different diseases, no article has recently reviewed the adverse events in all populations. Aim To evaluate the safety of MSC therapy in all populations receiving MSC therapy and explore the potential heterogeneities influencing the clinical application of MSCs. Methods The PubMed, Embase, Web of Science and Scopus databases were searched from onset until 1 March 2021. Results All adverse events are displayed as odds ratios (ORs) and 95% CIs (confidential intervals). In total, 62 randomized clinical trials were included that enrolled 3546 participants diagnosed with various diseases (approximately 20 types of diseases) treated with intravenous or local implantation versus placebo or no treatment. All studies were of high quality, and neither serious publication bias nor serious adverse events (such as death and infection) were discovered across the included studies. The pooled analysis demonstrated that MSC administration was closely associated with transient fever (OR, 3.65, 95% CI 2.05–6.49, p < 0.01), administration site adverse events (OR, 1.98, 95% CI 1.01–3.87, p = 0.05), constipation (OR, 2.45, 95% CI 1.01–5.97, p = 0.05), fatigue (OR, 2.99, 95% CI 1.06–8.44, p = 0.04) and sleeplessness (OR, 5.90, 95% CI 1.04–33.47, p = 0.05). Interestingly, MSC administration trended towards lowering rather than boosting the incidence rate of arrhythmia (OR, 0.62, 95% CI 0.36–1.07, p = 0.09). Conclusions Conclusively, MSC administration was safe in different populations compared with other placebo modalities.

scholarly journals Optimal treatment strategy of fremanezumab in migraine prevention: a systematic review with network meta-analysis of randomized clinical trials

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
I-Hsin Huang ◽  
Po-Chien Wu ◽  
Ya-Han Lee ◽  
Yi-No Kang
Keyword(s):  
Adverse Events ◽  
Treatment Strategy ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Reduction Rate ◽  
High Dose ◽  
Efficacy And Safety ◽  
Serious Adverse Events ◽  
Mean Differences

Abstract Identifying the optimal fremanezumab treatment strategy is crucial in treating patients with migraines. The optimal strategy was investigated by assessing the cumulative 50% reduction rate (50%CRR), cumulative 75% reduction rate (75%CRR), reduction in the number of migraine days, treatment-related adverse events, and serious adverse events in patients treated with fremanezumab 225 mg monthly (225 mg), 675 mg monthly (675 mg), 900 mg monthly (900 mg), a single high dose of 675 mg (S675mg), 675 mg at baseline with 225 mg monthly (675/225 mg), and placebo. Biomedical databases were searched for randomized controlled trials on this topic, and data were individually extracted. Risk ratios and mean differences were used to present the pooled results. The surface under the cumulative ranking curve (SUCRA) was used to determine the effects of the medication strategies of fremanezumab. Five trials (n = 3404) were used to form a six-node network meta-analysis. All fremanezumab medication strategies displayed significantly higher cumulative 50% reduction rates than the placebo. The SUCRA revealed that treatment with 675 mg yielded the highest 50%CRR value (mean rank = 2.5). S675 mg was the only treatment with significantly higher 75%CRR reduction rate than placebo, whereas the SUCRA for 225 mg displayed the highest mean rank (2.2). Moreover, 225 mg (mean rank = 2.2) and S675 mg (mean rank = 2.2) presented lower probabilities of serious adverse events. Collectively, S675mg and 225 mg exhibited the optimal balance between efficacy and safety within three months. Long-term efficacy and safety remain unclear, and future studies should further evaluate the long-term outcomes.

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