Network Meta-analysis of Treatments for Chronic Plaque Psoriasis in Canada

2014 ◽  
Vol 18 (6) ◽  
pp. 371-378 ◽  
Author(s):  
Aditya K. Gupta ◽  
Deanne Daigle ◽  
Danika C.A. Lyons
Keyword(s):  
Clinical Trials ◽  
Plaque Psoriasis ◽  
Meta Analysis ◽  
Severity Index ◽  
Phase Iii ◽  
Chronic Plaque Psoriasis ◽  
Phase Iii Clinical Trials ◽  
Statistical Framework ◽  
Consistency Model ◽  
Systemic Treatments

Background: Psoriasis affects approximately 500,000 Canadians. Eight treatments are currently licensed for chronic plaque psoriasis in Canada. Objective: To compare the efficacy of systemic treatments for chronic plaque psoriasis for the outcome > 75% reduction in the Psoriasis Area and Severity Index (PASI) using network meta-analysis. Methods: PubMed and clinicaltrials.gov databases were searched up until October 15, 2013, for phase III clinical trials. A consistency model based on a random-effects bayesian statistical framework was used to compare the rates of > 75% PASI reduction across trials. Results: Twenty-one studies were included in the network analysis. Infliximab had significantly greater odds of producing > 75% reduction in the PASI compared to all treatments. All treatments conferred greater odds of > 75% PASI reduction compared to placebo. Conclusion: Although infliximab had the highest efficacy relative to other systemic treatments for psoriasis, adverse effects, cost, and patient preferences should also be considered when deciding on treatment.

Risankizumab for the Treatment of Moderate to Severe Plaque Psoriasis

2019 ◽  
Vol 54 (4) ◽  
pp. 380-387 ◽  
Author(s):  
Wendy Li ◽  
Rima Ghamrawi ◽  
Wasim Haidari ◽  
Steven R. Feldman
Keyword(s):  
Clinical Trials ◽  
Phase Ii ◽  
Plaque Psoriasis ◽  
Data Extraction ◽  
Severity Index ◽  
Phase Iii ◽  
Cochrane Library ◽  
Severe Plaque Psoriasis ◽  
Phase Iii Clinical Trials ◽  
Interleukin 23

Objective: Risankizumab (Skyrizi), an interleukin-23 (IL-23) antagonist, was approved by the Food and Drug Administration (FDA) for the treatment of moderate to severe plaque psoriasis in April 2019. This article will review phase II and III clinical trials to assess the efficacy, safety, and clinical application of this drug. Data Sources: A systematic literature review was performed using the terms “psoriasis AND risankizumab” in the OVID MEDLINE, PubMed, Cochrane Library, EMBASE, and Web of Science databases. ClinicalTrials.gov was searched to identify ongoing or nonpublished studies. Study Selection and Data Extraction: Articles written in English between January 2000 and October 2019 discussing phase II and phase III clinical trials were evaluated. Data Synthesis: By the primary end point at week 16 in phase III trials, more patients achieved Psoriasis Area and Severity Index 90 receiving 150 mg risankizumab (72%-75%) compared with placebo (2.0%-4.9%, P < 0.001), 45 or 90 mg ustekinumab (42.0%-48%, P < 0.0001), and 40 mg adalimumab (47%, P < 0.0001). More patients achieved a static Physician’s Global Assessment score of 0 or 1 receiving 150 mg risankizumab (84%-88%) compared with placebo (5.1%-7.8%, P < 0.001), 45 or 90 mg ustekinumab (62%-63%, P < 0.0001), and 40 mg adalimumab (60%, P < 0.0001). Risankizumab was well tolerated across all studies. Conclusion: Risankizumab is a newly FDA-approved IL-23 inhibitor that shows particular promise in the treatment of plaque psoriasis. Based on this review, it is an effective and safe addition to the armamentarium of biologics that are currently available.

Reno-vascular toxicities associated with carfilzomib: Systematic review and meta-analysis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21622-e21622
Author(s):  
Chintan Shah ◽  
Harini Bejjanki ◽  
Rohit Bishnoi ◽  
Ankur Jain ◽  
Subhankar Samal ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Phase I ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Dose Effect ◽  
Phase Iii ◽  
Control Group ◽  
Phase Iii Clinical Trials

e21622 Background: Carfilzomib (Carf) is a novel proteasome inhibitor that is approved for patients with relapsed multiple myeloma (RMM) who have failed ≥ 1 prior lines of therapy. The incidence and seriousness of Carf associated reno-vascular toxicities (RVT) is not well known. We performed systematic review of Carf literature with meta-analysis to determine its incidence and overall risk. Methods: Initial search of literature led to a total of 175 Carf related articles. However, we used a total of 29 publications; phase I/II, phase II and phase III clinical trials (n = 3) which used Carf as monotherapy or in combination. We excluded phase I studies. Incidence rates and odds ratios (OR) were calculated with either fixed effect or random effect model based on the heterogeneity of included studies. Toxicity such as hypertension (HTN), renal failure (RF) and venous thromboembolism (VTE) were reported according to CTCAE v4.0. Results: A total of 4560 patients with various hematological and solid malignancies were included. Incidences of toxicities were: 15.9% and 4.7 % for HTN, 11.2% and 3.44% for RF, 6.47% and 2.22% for VTE, respectively for all grades and high grades in each category. When compared to control group taken from phase III clinical trials, the risk of HTN and RF due to Carf was significantly higher [OR = 2.91 and 3.32 in HTN (P < 0.001)], [OR = 1.71 and 1.79 (P < 0.05) for RF], respectively for all grade and high grade in each category. Moreover, incidence of HTN with higher than standard dose of carf (27 mg/m2 twice weekly) was significantly higher (P < 0.001). RF and VTE did not have the dose effect. Concomitant use of immunomodulator (IMiD) significantly increased, as expected, the incidence of VTE (P < 0.001). There was no variation in the incidence of RVT among newly diagnosed versus RMM (P = 0.4). Conclusions: Overall incidence and risk of hypertension and renal toxicities seems to be high when using Carf. Higher doses of Carf seem to lead to higher incidence of HTN, while the risk of VTE is higher with concomitant IMiD use. The pathophysiology for these complications is poorly understood, however it could be secondary to endothelial effect of carf. Physician should be vigilant about these effects as it can lead to poor overall outcomes.

The prognostic impact of KRAS mutation in colorectal cancer patients: A meta-analysis of phase III clinical trials.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. e14515-e14515 ◽  
Author(s):  
Clarinda Wei Ling Chua ◽  
Dawn QQ Chong ◽  
Ravindran Kanesvaran ◽  
Wai Meng David Tai ◽  
Chee Kian Tham ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trials ◽  
Cancer Patients ◽  
Kras Mutation ◽  
Meta Analysis ◽  
Phase Iii ◽  
Prognostic Impact ◽  
Phase Iii Clinical Trials ◽  
Colorectal Cancer Patients

Speed of Psoriasis Treatment Response for Biologic Agents: A Review of Phase III Clinical Trials

2021 ◽  
pp. 247553032199908
Author(s):  
Matthew C. Johnson ◽  
Courtney E. Heron ◽  
Rima I. Ghamrawi ◽  
Esther A. Balogh ◽  
Steven R. Feldman
Keyword(s):  
Clinical Trials ◽  
Treatment Response ◽  
Clinical Trial Data ◽  
Severity Index ◽  
Biologic Agents ◽  
Phase Iii ◽  
Interleukin 17 ◽  
Cost Of Treatment ◽  
Phase Iii Clinical Trials ◽  
Speed Of Response

Background: Clinical trials often focus on the efficacy of biologic agents in the treatment of psoriasis without emphasis on the speed of response. Objective: We evaluated clinical trial data to determine which biologic agents achieve the fastest treatment response. Methods: A review of phase III clinical trials of biologic agents in psoriasis was performed. Speed was determined by analyzing Psoriasis Area and Severity Index (PASI) 75/90 responder curves to estimate the point at which 50% of subjects achieved that outcome, PASI 75/9050. Time to achieve PASI 75/9050 was averaged across trials. Results: Time to achieve PASI 7550, in weeks: brodalumab 210 mg, 3.5; ixekizumab 80 mg Q2 W, 4; secukinumab 300 mg, 5; infliximab 5mg/kg, 5.5; risankizumab 150 mg, 6; guselkumab 100 mg, 6.25; adalimumab 40 mg, 7.25; ustekinumab 45/90 mg, 7.4; certolizumab 400 mg, 7.5; tildrakizumab 100 mg, 9; etanercept 50 mg, 12.5. PASI 9050 responder rate estimations revealed a similar trend. Conclusion: Interleukin-17 inhibitors have a more rapid treatment response compared with other classes. Although speed is important, efficacy, persistence, side effects, cost of treatment, and number of injections are all factors to consider.

Efficacy and toxicity of CDK 4/6 inhibitors in breast cancer: Systematic review and meta-analysis of the phase III clinical trials.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14591-e14591 ◽  
Author(s):  
Faheem Farooq ◽  
Jules A. Cohen
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Meta Analysis ◽  
Treatment Discontinuation ◽  
Phase Iii ◽  
Cochrane Library ◽  
Line Treatment ◽  
Treatment Trials ◽  
Phase Iii Clinical Trials ◽  
Grade 3

e14591 Background: Selective CDK4/6 inhibitors such as palbociclib, abemaciclib, and ribociclib have demonstrated efficacy in advanced HR+/HER2- breast cancer. Drug-related toxicity has been manageable, but variable amongst the drugs. This meta-analysis was conducted to guide CDK inhibitor choice based on efficacy and toxicity. Methods: A systematic literature review of Pubmed, Cochrane Library, and EMBASE was performed in December 2018. Efficacy was evaluated via reported progression free survival (PFS) and pooled hazard ratios (HR). Overall response rate (ORR), treatment discontinuation, and treatment-related adverse events (AEs) were measured via pooled odds ratios (OR). Meta-analyses were performed using random effects modeling and 95% confidence intervals (CI). Results: A pooled analysis of 7 phase III clinical trials (n = 4415) demonstrated a HR of 0.55 (CI: 0.51-0.60) for PFS and an OR of 1.93 (CI: 1.54-2.42) for ORR. First-line treatment trials (n = 3020) pairing CDK 4/6 inhibitors with NSAI/tamoxifen had a HR of 0.56 (CI: 0.51-0.60) for prolonged PFS and an OR of 1.64 (CI: 1.39-1.95) for ORR. Second-line treatment trials (n = 1916) pairing CDK 4/6 inhibitors with fulvestrant had an HR of 0.54 (CI: 0.48-0.61) for prolonged PFS and an OR of 2.48 (CI: 1.57-3.90) for ORR. Palbociclib and ribociclib had similar rates of grade 3/4 AEs, neutropenia, and treatment discontinuation. Abemaciclib had lower rates of grade 3/4 AEs overall, but significantly increased rates of diarrhea and treatment discontinuation due to AEs. Conclusions: Each drug demonstrated a significant improvement in PFS. However, there is no statistical difference in efficacy among the three CDK inhibitors. Treatment decisions can be guided by the tolerability of AEs amongst the medications. Further patient follow-up will illuminate whether there is an OS advantage in this novel drug class. [Table: see text]

scholarly journals Efficacy and Safety of COVID-19 Vaccines in Phase III Trials: A Meta-Analysis

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 582
Author(s):  
Haoyue Cheng ◽  
Zhicheng Peng ◽  
Wenliang Luo ◽  
Shuting Si ◽  
Minjia Mo ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Meta Analysis ◽  
Phase Iii ◽  
Cochrane Library ◽  
Efficacy And Safety ◽  
Common People ◽  
Random Effects Models ◽  
Phase Iii Clinical Trials ◽  
Phase Iii Trials

Nowadays, the vaccination with COVID-19 vaccines is being promoted worldwide, professionals and common people are very concerned about the efficacy and safety of COVID-19 vaccines. No published systematic review and meta-analysis has assessed the efficacy and safety of the COVID-19 vaccines based on data from phase III clinical trials. Therefore, this study has estimated the efficacy and safety of COVID-19 vaccines and the differences between vaccine types. PubMed, Embase, the Cochrane Library, CNKI, Wanfang, medRxiv databases and two websites were used to retrieve the studies. Random-effects models were used to estimate the pooled efficacy and safety with risk ratio (RR). A total of eight studies, seven COVID-19 vaccines and 158,204 subjects were included in the meta-analysis. All the vaccines had a good preventive effect on COVID-19 (RR = 0.17, 95% CI: 0.09–0.32), and the mRNA vaccine (RR = 0.05, 95% CI: 0.03–0.09) was the most effective against COVID-19, while the inactivated vaccine (RR = 0.32, 95% CI: 0.19–0.54) was the least. In terms of safety, the risk of overall adverse events showed an increase in the vaccine group after the first (RR = 1.46, 95% CI: 1.03–2.05) or second (RR = 1.52, 95% CI: 1.04–2.20) injection. However, compared with the first injection, the risk of local (RR = 2.64, 95% CI: 1.02–6.83 vs. RR = 2.25, 95% CI: 0.52–9.75) and systemic (RR = 1.33, 95% CI: 1.21–1.46 vs. RR = 1.59, 95% CI: 0.84–3.01) adverse events decreased after the second injection. As for the mRNA vaccine, the risk of overall adverse events increased significantly, compared with the placebo, no matter whether it was the first (RR = 1.83, 95% CI = 1.80–1.86) or the second (RR = 2.16, 95% CI = 2.11–2.20) injection. All the COVID-19 vaccines that have published the data of phase III clinical trials have excellent efficacy, and the risk of adverse events is acceptable. The mRNA vaccines were the most effective against COVID-19, meanwhile the risk and grade of adverse events was minimal, compared to that of severe symptoms induced by COVID-19.

Clinical Efficacy of Efalizumab in Patients with Chronic Plaque Psoriasis: Results from Three Randomized Placebo-Controlled Phase III Trials: Part I

2005 ◽  
Vol 9 (6) ◽  
pp. 303-312 ◽  
Author(s):  
David M. Pariser ◽  
Kenneth B. Gordon ◽  
Kim A. Papp ◽  
Craig L. Leonardi ◽  
Paul Kwon ◽  
...  
Keyword(s):  
Plaque Psoriasis ◽  
Statistical Significance ◽  
Symptom Control ◽  
Severity Index ◽  
Phase Iii ◽  
Chronic Plaque Psoriasis ◽  
Multicenter Studies ◽  
Double Blind ◽  
Phase Iii Trials ◽  
The Individual

Background: Effective psoriasis therapies are needed for long-term symptom control. ObjectiveAssess efalizumab (Raptiva®) efficacy in a large cohort of psoriasis patients. Methods: Data from three Phase III, randomized, double-blind, parallel-group, placebo-controlled, multicenter studies were pooled. Patients ( n = 1,651) with moderate to severe plaque psoriasis received 12 weeks of subcutaneous efalizumab 1 or 2 mg/kg/wk or placebo. Remits: All efficacy measures reached statistical significance within each of the individual studies ( p < 0.001) and overall. More efalizumab-treated patients achieved > 75% and ≥ 50% Psoriasis Area and Severity Index (PASI) improvement at week 12 than did placebo-treated patients (27.8% vs 3.8% [ p < 0.001] and 56.1% vs 14.6% [ p < 0.001], respectively). Significant PASI improvements occurred as early as week 2 (12.5% vs 7.9%, p =0.0001). Adverse events were generally mild to moderate. Conclusion: Efalizumab resulted in early and significant improvement for all efficacy endpoints and was well tolerated in patients with moderate to severe chronic plaque psoriasis.

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