title: Impact of biologic therapies on risk of major adverse cardiovascular events in patients with psoriasis: systematic review and meta-analysis of randomized controlled trials.
abstract: Concerns have been raised regarding an increased risk of major adverse cardiovascular events (MACEs) (myocardial infarction, cerebrovascular accident or cardiovascular death) in patients treated with anti-interleukin (IL)-12/23 agents for moderate-to-severe psoriasis. We aimed to examine the risk of MACEs in adult patients with plaque psoriasis that are exposed to biologic therapies via a meta-analysis of randomized controlled trials (RCTs). Data were obtained from systematic searches in the Cochrane Library, MEDLINE and Embase, U.S. Food and Drug Administration, European Medicines Agency, individual pharmaceutical companies online search platforms and five trials registers (up to 31 March 2016). We selected RCTs reporting adverse events in adults with plaque psoriasis receiving at least one licensed dose of biologic therapy, conventional systematic therapy or placebo. We calculated Peto odds ratios (ORs) with 95% confidence intervals (CIs) and calculated I2statistics to assess heterogeneity. Overall, 38 RCTs involving 18 024 patients were included. No MACEs were observed in 29 studies, while nine RCTs reported 10 patients experiencing MACEs. There was no statistically significant difference in risk of MACEs associated with the use of biologic therapies overall (OR 1·45, 95% CI 0·34-6·24); tumour necrosis factor-α inhibitors (adalimumab, etanercept and infliximab) (OR 0·67, 95% CI 0·10-4·63); anti-IL-17A agents (secukinumab and ixekizumab) (OR 1·00, 95% CI 0·09-11·09) or ustekinumab (OR 4·48, 95% CI 0·24-84·77). No heterogeneity was observed in these comparisons. In conclusion, the limited existing evidence suggests that licensed biologic therapies are not associated with MACEs during the short randomized controlled periods in clinical trials.
authors: Centre for Pharmacoepidemiology and Drug Safety, Manchester Pharmacy School, University of Manchester, Manchester, M13 9PT, U.K.
authors: W
authors: W
authors: Rungapiromnan
authors: Centre for Pharmacoepidemiology and Drug Safety, Manchester Pharmacy School, University of Manchester, Manchester, M13 9PT, U.K.|Dermatology Centre, Salford Royal NHS Foundation Trust, University of Manchester, Manchester Academic Health Science Centre, Manchester, U.K.
authors: Z Z N
authors: ZZN
authors: Yiu
authors: Dermatology Centre, Salford Royal NHS Foundation Trust, University of Manchester, Manchester Academic Health Science Centre, Manchester, U.K.
authors: R B
authors: RB
authors: Warren
authors: Dermatology Centre, Salford Royal NHS Foundation Trust, University of Manchester, Manchester Academic Health Science Centre, Manchester, U.K.
authors: C E M
authors: CEM
authors: Griffiths
authors: Centre for Pharmacoepidemiology and Drug Safety, Manchester Pharmacy School, University of Manchester, Manchester, M13 9PT, U.K.
authors: D M
authors: DM
authors: Ashcroft
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects; D001685:Biological Factors / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D016757:Death, Sudden, Cardiac / Q000209:etiology; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000037:antagonists & inhibitors; D020381:Interleukin-17 / Q000037:antagonists & inhibitors; D053759:Interleukin-23 / Q000037:antagonists & inhibitors; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced; D011565:Psoriasis / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D020521:Stroke / Q000139:chemically induced; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D001685:Biological Factors; C508717:IL17A protein, human; D020381:Interleukin-17; D053759:Interleukin-23; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12