title: Risk of infections using anti-TNF agents in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: a systematic review and meta-analysis.
abstract: Five anti-tumor necrosis factor (anti-TNF) agents have received regulatory approval for use in rheumatology: adalimumab, golimumab, infliximab, certolizumab, and etanercept. Apart from their well-documented therapeutic value, it is still uncertain to what extent they are associated with an increased risk of infectious adverse events. Areas covered: We conducted a systematic review and meta-analysis of published randomized studies to determine the effect of anti-TNF drugs on the occurrence of infectious adverse events (serious infections; tuberculosis; opportunistic infections; any infection). We searched Medline, Embase, and the Cochrane Library up to May 2014 to identify eligible studies in adult patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis that evaluated anti-TNF drugs compared with placebo or no treatment. Expert opinion: Our study encompassed data from 71 randomized controlled trials involving 22,760 participants (range of follow-up: 1-36 months) and seven open label extension studies with 2,236 participants (range of follow-up: 6-48 months). Quantitative synthesis of the available data found statistically significant increases in the occurrence of any infections (20%), serious infections (40%), and tuberculosis (250%) associated with anti-TNF drug use, while the data for opportunistic infections were scarce. The quality of synthesized evidence was judged as moderate. Further evidence from registries and long-term epidemiological studies are needed to better define the relationship between anti-TNF agents and infection complications.
authors.affiliation: a Department of Epidemiology , Lazio Regional Health Service , Rome , Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Minozzi
authors.affiliation: b Humanitas Clinical and Research Center , Milan , Italy.
authors.forename: Stefanos
authors.initials: S
authors.lastname: Bonovas
authors.affiliation: c Department of Experimental and Health Sciences , Universitat Pompeu Fabra , Barcelona , Spain.|d Centre for Research in Environmental Epidemiology , Barcelona , Spain.|e Hellenic Centre for Disease Control and Prevention , Athens , Greece.
authors.forename: Theodore
authors.initials: T
authors.lastname: Lytras
authors.affiliation: f Clinical Epidemiology Unit , IRCCS Galeazzi Orthopedic Institute , Milan , Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Pecoraro
authors.affiliation: g Department of Biomedical Sciences for Health , University of Milan , Milan , Italy.
authors.forename: Marien
authors.initials: M
authors.lastname: González-Lorenzo
authors.affiliation: h Postgraduate School of Public Health , University of Milan , Milan , Italy.
authors.forename: Anan Judina
authors.initials: AJ
authors.lastname: Bastiampillai
authors.affiliation: h Postgraduate School of Public Health , University of Milan , Milan , Italy.
authors.forename: Eugenia Maria
authors.initials: EM
authors.lastname: Gabrielli
authors.affiliation: h Postgraduate School of Public Health , University of Milan , Milan , Italy.
authors.forename: Andrea Carlo
authors.initials: AC
authors.lastname: Lonati
authors.affiliation: f Clinical Epidemiology Unit , IRCCS Galeazzi Orthopedic Institute , Milan , Italy.|g Department of Biomedical Sciences for Health , University of Milan , Milan , Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moja
authors.affiliation: i Methodology of Systematic Reviews and Guidelines Development Unit, Department of Oncology , IRCCS Mario Negri Institute for Pharmacological Research , Milan , Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Cinquini
authors.affiliation: j Medical Department , Pfizer , Rome , Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Marino
authors.affiliation: k Immunoallergology Unit, Department of Biomedicine, Azienda Ospedaliero-Universitaria Careggi , Florence , Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Matucci
authors.affiliation: l Department of Pediatric Hematology , Oncology and Transplant Unit, IRCCS Ospedale Pediatrico Bambino Gesù , Rome , Italy.
authors.forename: Giuseppe Maria
authors.initials: GM
authors.lastname: Milano
authors.affiliation: m Hypertension Unit, Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology , University of Rome Sapienza , Sant'Andrea Hospital, Rome , Italy.|n IRCCS Neuromed , Pozzilli , Rome , Italy.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Tocci
authors.affiliation: o Rheumatology Research Unit, Department of Clinical Medicine and Surgery , University of Naples Federico II , Naples , Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Scarpa
authors.affiliation: p Translational Research Unit, Department of Epidemiology and Preclinical Research , National Institute for Infectious Diseases , Rome , Italy.
authors.forename: Delia
authors.initials: D
authors.lastname: Goletti
authors.affiliation: q Division of Rheumatology , Misericordia e Dolce Hospital , Prato , Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Cantini
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D015535:Arthritis, Psoriatic / Q000188:drug therapy; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D006801:Humans; D007239:Infections / Q000139:chemically induced* / Q000453:epidemiology; D016032:Randomized Controlled Trials as Topic; D013167:Spondylitis, Ankylosing / Q000188:drug therapy; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha
keywords: Ankylosing spondylitis; anti-TNF drugs; drug safety; infections; meta-analysis; opportunistic infections; psoriatic arthritis; rheumatoid arthritis; serious infections; systematic review; tuberculosis