title: Risk of malignancies using anti-TNF agents in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: a systematic review and meta-analysis.
abstract: Malignancies have been reported in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, treated with anti-tumour necrosis factor (anti-TNF) agents. Areas covered: We conducted a systematic review of randomized controlled trials (RCTs) to determine the effect of anti-TNF agents on the occurrence of cancer (any type). Literature databases were searched up to May 2014 to identify relevant studies that evaluated adalimumab, certolizumab, etanercept, golimumab, or infliximab, compared with placebo or no treatment. Data on cancer occurrence were extracted at the maximum follow-up time reported. Expert opinion: Fifty-five RCTs with 20,631 patients met the eligibility criteria. Of these, 32 trials with 15,539 patients reported at least one case of cancer, for a total of 112 malignancies. The degree of variability between studies was consistent with what would be expected to occur by chance alone. There was no evidence of an association between anti-TNF agents and cancer risk (fixed-effects model (OR: 1.31, 95% CI: 0.89, 1.95); a random-effects model (OR: 1.16, 95% CI: 0.75, 1.81)). We found evidence of selective outcome reporting or publication bias suggesting that the pooled effect estimate for cancer may have been overestimated. The evidence is imprecise, and the risk of bias was high or unclear across primary studies.
authors.affiliation: a Humanitas Clinical and Research Center , Milan , Italy.
authors.forename: Stefanos
authors.initials: S
authors.lastname: Bonovas
authors.affiliation: b Department of Epidemiology , Lazio Regional Health Service , Rome , Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Minozzi
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 Department of Biomedical Sciences for Health , University of Milan , Milan , Italy.
authors.forename: Marien
authors.initials: M
authors.lastname: González-Lorenzo
authors.affiliation: g Clinical Epidemiology Unit, IRCCS Galeazzi Orthopedic Institute , Milan , Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Pecoraro
authors.affiliation: h Postgraduate School of Public Health , University of Milan , Milan , Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Colombo
authors.affiliation: h Postgraduate School of Public Health , University of Milan , Milan , Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Polloni
authors.affiliation: f Department of Biomedical Sciences for Health , University of Milan , Milan , Italy.|g Clinical Epidemiology Unit, IRCCS Galeazzi Orthopedic Institute , 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 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: l Immunoallergology Unit, Department of Biomedicine, Azienda Ospedaliero-Universitaria Careggi , Florence , Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Matucci
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 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: p 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: q Division of Rheumatology , Misericordia e Dolce Hospital , Prato , Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Cantini
mesh_terms: 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; D009369:Neoplasms / Q000453:epidemiology / Q000209:etiology*; D017594:Publication Bias; 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: Adverse events; ankylosing spondylitis; anti-TNF drugs; cancer; drug safety; malignancy; meta-analysis; psoriatic arthritis; rheumatoid arthritis; systematic review