Journal ArticleDOI
Association Between Biologic Therapies for Chronic Plaque Psoriasis and Cardiovascular Events: A Meta-analysis of Randomized Controlled Trials
Caitriona Ryan,Craig L. Leonardi,James G. Krueger,Alexa B. Kimball,Bruce Strober,Kenneth B. Gordon,Richard G. Langley,James A. de Lemos,Yahya Daoud,Derek M. Blankenship,Salahuddin Kazi,Daniel H. Kaplan,Vincent E. Friedewald,Alan Menter +13 more
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TLDR
There was no significant difference in the rate of MACEs observed in patients receiving anti-IL-12/IL-23 antibodies or anti-TNF-α treatments in adults, and this study may have been underpowered to identify a significant difference.Abstract:
Context Ustekinumab and briakinumab, monoclonal antibodies to the shared p40 subunit of interleukin (IL)-12 and IL-23, have shown efficacy in treating chronic plaque psoriasis (CPP). Preliminary reports of major adverse cardiovascular events (MACEs) in psoriasis patients receiving anti–IL-12/23 agents have prompted concern. Objective To evaluate a possible association between biologic therapies for CPP and MACEs via meta-analysis. Data Sources Randomized controlled trials (RCTs) of anti–IL-12/23 (ustekinumab and briakinumab) agents and anti–tumor necrosis factor α (TNF-α) agents (adalimumab, etanercept, and infliximab) used in treating CPP were reviewed using the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and Ovid MEDLINE from database inception to May 2011. The results of registered nonpublished completed studies were procured through abstract publications or poster presentations. Study Selection Randomized, placebo-controlled, double-blind, monotherapy studies (with safety outcome data for MACE) of IL-12/23 antibodies and anti–TNF-α agents in adults. Studies of psoriatic arthritis were excluded. Data Extraction Two investigators independently searched data while 6 investigators reviewed the abstracted data. Results A total of 22 RCTs comprising 10 183 patients met the predefined inclusion criteria. The primary outcome measure was MACE, a composite end point of myocardial infarction, cerebrovascular accident, or cardiovascular death during the placebo-controlled phase of treatment in patients receiving at least 1 dose of study agent or placebo. Absolute risk differences were used as an effect measure. There was no evidence of statistical heterogeneity across the studies using the I 2 statistic (I 2 = 0), allowing for combination of trial results using the Mantel-Haenszel fixed-effects method. During the placebo-controlled phases of the anti–IL-12/23 studies, 10 of 3179 patients receiving anti–IL-12/23 therapies experienced MACEs compared with zero events in 1474 patients receiving placebo (Mantel-Haenszel risk difference, 0.012 events/person-year; 95% confidence interval [CI], −0.001 to 0.026; P =.12). In the anti–TNF-α trials, only 1 of 3858 patients receiving anti–TNF-α agents experienced a MACE compared with 1 of 1812 patients receiving placebo (Mantel-Haenszel risk difference, −0.0005 events/person-year; 95% CI, −0.010 to 0.009; P = .94). Conclusions Compared with placebo, there was no significant difference in the rate of MACEs observed in patients receiving anti–IL-12/IL-23 antibodies or anti–TNF-α treatments. This study may have been underpowered to identify a significant difference.read more
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Long-term safety of ustekinumab in patients with moderate-to-severe psoriasis: final results from 5 years of follow-up.
Kim A. Papp,Christopher E.M. Griffiths,Kenneth B. Gordon,Mark Lebwohl,Philippe Szapary,Y. Wasfi,Daphne Chan,M-C Hsu,Ho,Pierre-Dominique Ghislain,Bruce Strober,Kristian Reich +11 more
TL;DR: Long‐term safety evaluations of biologics are needed to inform patient management decisions and should be considered in clinical practice, according to a report in JAMA Oncology.
Journal ArticleDOI
Psoriasis and Major Adverse Cardiovascular Events: A Systematic Review and Meta-Analysis of Observational Studies
TL;DR: Mild and severe psoriasis are associated with an increased risk of myocardial infarction and stroke, and future studies should include more complete covariate adjustment and characterization of Psoriasis severity.
Journal ArticleDOI
Anti-inflammatory therapies for atherosclerosis
Magnus Bäck,Göran K. Hansson +1 more
TL;DR: Data from observational or small interventional studies evaluating surrogate markers of disease activity are crucial to understand the role of inflammation in atherosclerosis, and to design randomized controlled studies to evaluate the effect of specific anti-inflammatory strategies on cardiovascular outcomes.
Journal ArticleDOI
The concept of psoriasis as a systemic inflammation: implications for disease management
TL;DR: A role for earlier and more appropriate treatment of psoriasis with drugs such as TNF‐α antagonists is indicated, which has the potential to significantly improve patient outcomes through the treatment of Psoriasis itself and possibly also in protection against co‐morbidities.
Journal ArticleDOI
The Inflammatory Response in Psoriasis: a Comprehensive Review
TL;DR: Significant challenges remain in developing safe and efficacious novel targeted therapies that depend on a better understanding of the immunological dysfunction in psoriasis, as well as developing increasingly efficient targeted treatment by blocking relevant inflammatory signaling pathways and molecules.
References
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