scholarly journals P182 A systematic literature review and network meta-analysis of the efficacy and safety of ixekizumab versus currently licensed biologics for the treatment of radiographic axSpA

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Yves Schymura ◽  
Peita Loiuse Graham-Clarke ◽  
Soyi Liu-Leage
Keyword(s):  
Literature Review ◽  
Systematic Literature Review ◽  
Odds Ratio ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Base Case ◽  
Efficacy And Safety ◽  
Biologic Therapies ◽  
Mixed Treatment ◽  
A Minor

Abstract Background/Aims  Patients with radiographic axial spondyloarthritis (rad-axSpA) are often managed using biologic therapies such as TNF-α inhibitors and interleukin-17 inhibitors, including ixekizumab (IXE). Due to a lack of head-to-head trial data, limited evidence exists as to the relative performance of biologic therapies. Therefore, when making evidence-based reimbursement decisions, treatment funding agencies can use network meta-analysis (NMA) to estimate the relative efficacy and safety of each treatment within a network of comparator treatments. Objectives: Demonstrate, by means of NMA, the efficacy and safety of IXE 80 mg administered every four weeks (Q4W) against other approved biologic agents used in the treatment of r-axSpA in a biologic-naïve population. Methods  We conducted a systematic literature review in February 2019 to identify relevant studies for inclusion in the NMA. The NMA was based on Bayesian Mixed Treatment Comparisons in keeping with NICE DSU (Decision Support Unit) technical guidance. The base case for this analysis focused on studies with biologic-naïve populations and assessed endpoints including the Assessment of SpondyloArthritis International Society endpoints (ASAS20 and ASAS40), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at least 50% improvement (BASDAI50), adverse events (AEs), serious adverse events (SAEs) and treatment discontinuation due to AE (DISCAE). Sensitivity analyses explored the robustness of the base case by including studies where the patient’s prior exposure to biologic therapy was unclear, not stated or mixed (treatment naïve and treatment experienced) and examined the impact of IXE starting dose (80mg v 160mg) on outcomes. Results  In total, the systematic literature review included 78 full papers and 27 conference proceedings. Fixed-effect models were chosen, as they had lower deviance information criteria (DICs) and random effects models frequently did not converge. IXE 80 mg Q4W demonstrated superiority to placebo on the ASAS20 (Odds Ratio: 3.72, 95% CI:2.11,6.68), ASAS40 (Odds Ratio: 6.26, 95% CI:3.37,11.69), BASDAI (Mean difference: -1.72, 95% CI:-2.27,-1.17) and the BASDAI 50 (Odds Ratio: 5.40, 95% CI: 2.91, 10.06) as well as the other efficacy measures investigated. IXE and the comparator treatments demonstrated similar efficacy compared to each other. The rate of AEs, SAEs and DISCAE were in line with the existing literature both for IXE and the comparator treatments. Results from the sensitivity analyses were confirmatory for the robustness of the base case results. Conclusion  This NMA confirms the efficacy and acceptable safety profile of IXE 80 mg Q4W and other biologics in biologic-naïve patients with active rad-axSpA. The NMA can be used to inform evidence-based decision-making in clinical practice and in payer decisions by including all currently marketed agents and dosages. Disclosure  Y. Schymura: Corporate appointments; Yves Schymura is an employ of Eli Lilly and Company. P. Graham-Clarke: Corporate appointments; Peita Louise Graham-Clarke is an employee of Eli Lilly and Company. Shareholder/stock ownership; Peita Louise Graham-Clarke is a minor shareholder of Eli Lilly and Company. S. Liu-Leage: Corporate appointments; Soyi Liu-Leage is an employ of Eli Lilly and Company. Shareholder/stock ownership; Soyi Liu-Leage is a minor shareholder of Eli Lilly and Comapny.

scholarly journals Efficacy and Safety of Rivaroxaban Compared with Other Therapies Used in Patients with Peripheral Artery Disease Undergoing Peripheral Revascularization: A Systematic Literature Review and Network Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Rupert Bauersachs ◽  
Olivia Wu ◽  
Neil Hawkins ◽  
Kevin Bowrin ◽  
Piotr Wojciechowski ◽  
...  
Keyword(s):  
Literature Review ◽  
Peripheral Artery Disease ◽  
Systematic Literature Review ◽  
Meta Analysis ◽  
Case Analysis ◽  
Base Case ◽  
Efficacy And Safety ◽  
Base Case Analysis ◽  
Peripheral Artery ◽  
Artery Disease

Background. The guidelines on antithrombotic treatment in patients with symptomatic peripheral artery disease (PAD) undergoing peripheral revascularization of the lower extremities were developed based on heterogeneous trials, assessing various dose regimens and recruiting patients who were subjected to different revascularization procedures. Objective. To compare efficacy and safety of treatments used in patients with PAD undergoing peripheral revascularization accounting for between-trial heterogeneity and large dispersion of the quality of evidence. Methods. A systematic literature review of randomised controlled trials (RCTs) recruiting adult patients with PAD receiving antithrombotics was conducted until January 2020. Hazard ratios (HR) were pooled using Bayesian network meta-analysis. The estimated between-treatment effects were presented as HR together with 95% credible intervals. The base case analysis included studies recruiting patients following recent peripheral revascularization, who received treatment regimens administered within the recommended therapeutic window, while a sensitivity scenario included all identified trials. Results. Thirteen RCTs were identified (8 RCTs enrolled patients following peripheral revascularization and 5 RCTs regardless of the previous revascularization). Five trials, recruiting an overall of 8349 patients, were considered for the base case analysis. Of those, 6564 patients were recruited in the VOYAGER PAD trial comparing rivaroxaban plus aspirin (RIV plus ASA) versus ASA. RIV plus ASA was associated with a lower risk of repeated peripheral revascularization versus ASA monotherapy ( HR = 0.88 [0.79, 0.99]), however having a trend towards an increased rate of major bleeding ( HR = 1.43 [0.98, 2.11]). There was no evidence for differences between RIV plus ASA and dual antiplatelet therapy and vitamin K antagonists plus ASA. Similar results were observed in sensitivity analyses. Conclusions. RIV plus ASA is associated with reduced risk of revascularization compared with ASA monotherapy, but the evidence for other comparators, in particular antiplatelet regimens, was insufficient to guide treatment decisions and highlights the challenge in establishing the magnitude of comparative efficacy using existing RCTs.

Efficacy and Safety Of Treatments For Relapsed Or Refractory Mantle Cell Lymphoma (MCL): Results Of a Systematic Literature Review

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5099-5099
Author(s):  
Annete Njue ◽  
Peter C Trask ◽  
Ann Colosia ◽  
Robert Olivares ◽  
Shahnaz Khan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Literature Review ◽  
Systematic Literature Review ◽  
Comparative Studies ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Patient Characteristics ◽  
Refractory Disease ◽  
Efficacy And Safety ◽  
Free Survival

Abstract Background MCL accounts for approximately 3%-10% of non-Hodgkin’s lymphoma (NHL) cases. The aggressive course of MCL includes rapid disease progression, with temporary responses to chemotherapy, and a high recurrence rate. However, the clinical course is variable with overall survival ranging from 6 months to more than 10 years. Although the median survival with MCL is 3-4 years, for those with relapsed or refractory disease, survival is much shorter. This systematic literature review (SLR) was designed to exhaustively collect and review information on the clinical efficacy and safety of the different interventions used in the treatment of refractory/relapsed MCL, and if possible to perform a meta-analysis. Methods Electronic databases (PubMed, Cochrane Library, Embase) were systematically searched for studies assessing the efficacy of safety of treatments for relapsed or refractory MCL published from 1997 to August 2, 2012. In addition, conference abstracts, bibliographic reference lists of included articles and recent reviews, and the Clinicaltrials.gov database were searched for phase 2, 3, or 4 studies displaying results, potentially unpublished in peer-reviewed journals. Main efficacy outcomes included objective response rate (ORR), complete response, partial response, duration of response, progression-free survival (PFS), and overall survival (OS). Safety endpoints focused on grade 3/4 toxicities and treatment withdrawals due to toxicity. Studies had to report on relapsed or refractory MCL after at least one standard treatment and patients who were not eligible to receive high-dose chemotherapy or stem cell transplant (autologous or allogeneic). Mixed type NHL studies were required to report MCL outcomes separately for inclusion. Results A total of 3,308 publications were identified in the first pass of a broad SLR on NHL; of these, 67 provided relevant data for MCL representing 59 unique studies. Of the 59 studies, 6 were comparative (including 5 RCTs) and 53 were noncomparative single-arm studies; 35 evaluated single-agent regimens, and 24 evaluated combination therapies. A total of 40 different treatments were evaluated in the identified studies. Overall survival and PFS were infrequently reported. Criteria for relapsed or refractory were often not defined, with only 7 studies providing varied definitions. The ORR of active treatments in the few comparative studies ranged from 6%-83%, with most estimates between 45% and 60%. Progression-free survival was approximately 5-7 months with the exception of bortezomib + CHOP in which a 16-month PFS was noted; median OS for these studies ranged from 11-16 months, with 36 months for the aforementioned exception. In the single-arm studies, ORR ranged from 12%-100%, with most estimates from 30%-60%. Progression-free survival was approximately 5-12 months, except for bendamustine alone or in combination (∼21 months) and bortezomib in combination (∼18 months, but with large variability). Overall survival ranged from 12-24 months, with two notable exceptions: bortezomib combination (∼38 months) and temsirolimus in combination with rituximab (∼30 months). Some increase in PFS and OS was observed over the study period. The main safety concerns were related to thrombocytopenia (11-66%), neutropenia (15-100%), anemia (4-34%), and neuropathy (9-13%). Although patients’ MIPI category was collected, outcomes were not reported by this variable. Conclusions The results of this SLR confirm that survival is still low among treatments for relapsed or refractory MCL making this a continued area of unmet need. The small number of randomized trials makes it difficult to identify a standard of care. The lack of common treatments among the randomized controlled trials for MCL and the variability in the populations studied did not allow for a valid meta-analysis. Small sample size, infrequent reporting of OS/PFS, limited information on prior treatments/responses, and patient characteristics also make comparison of results difficult. Comparative studies demonstrating relative survival advantages of various therapies in relapsed or refractory MCL are needed, as is more information on the relation between MIPI scores and outcomes. In the absence of such evidence, management of relapsed or refractory disease should be based on individual patient characteristics and concerns regarding tolerability. Disclosures: Njue: RTI Health Solutions: Employment. Trask:Sanofi: Employment. Colosia:RTI Health Solutions: Employment. Olivares:Sanofi: Employment. Khan:RTI Health Solutions: Employment. Abbe:Sanofi: Employment. Police: RTI Health Solutions: Employment. Wang:RTI Health Solutions: Employment. Sherrill:RTI Health Solutions: Employment. Kaye:RTI Health Solutions: Employment. Awan:Lymphoma Research Foundation (Career Development Award): Research Funding.

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