title: Safety of biologic DMARDs in RA patients in real life: A systematic literature review and meta-analyses of biologic registers.
abstract: OBJECTIVE
  In daily practice, safety in rheumatoid arthritis (RA) patients receiving biological treatment is an important issue. Unlike randomized controlled trials, biologic registers provide long-term real life safety data. To identify all biologic registers worldwide, to extract and analyze data regarding safety in RA patients under biologics.
  
  
  METHODS
  Systematic review was performed independently by 2 rheumatologists using PUBMED, COCHRANE Library and EMBASE databases, up to December 2014. Worldwide biologic registers and related publications were identified. Data on safety issues in RA patients were extracted for meta-analyses. Random-effect meta-analyses were performed to estimate risk ratios (RRs) of mortality, cardiovascular events, cancer, including lymphoma and melanoma and serious infections between (1) biological and non-biological DMARD (cDMARD), (2) between biologics when data were available.
  
  
  RESULTS
  Forty-three biological registers were identified worldwide and 27 publications were included for safety meta-analyses on anti-TNFs. Compared to cDMARD, mortality and cardiovascular events were significantly decreased in patients treated with anti-TNFs: RR=0.60 [95% CI 0.38-0.94] and RR=0.62 [0.44-0.88], respectively. Anti-TNFs did not increase the risk of solid cancer in patients without or with prior malignancy (RR=0.84 [0.60-1.18] and RR=0.77 [0.29-2.03], respectively), lymphoma (RR=0.90 [0.62-1.31]) and melanoma (RR=1.17 [0.86-1.59]). As expected, serious infections were significantly increased during anti-TNF treatment (RR=1.48 [1.18-1.85]) compared to cDMARD. No significant difference was found between soluble receptor to TNF and monoclonal antibodies (RR=0.55 [0.22-1.35]).
  
  
  CONCLUSIONS
  By reducing dramatically chronic inflammation in RA patients, anti-TNFs decrease mortality, cardiovascular events without increase significantly the risk of cancer, compared to cDMARDs.
authors.affiliation: Rheumatology Department and IPROS, Orleans Hospital, 14, avenue de l'Hôpital, CS 86706, 45067 Orleans cedex 2, France; EA4708 Orleans University, 45067 Orleans cedex 2, France.
authors.forename: Maïté
authors.initials: M
authors.lastname: de La Forest Divonne
authors.affiliation: Rheumatology Department, National Center for Rare Systemic Autoimmune Diseases, hôpital de Hautepierre, hôpitaux universitaires de Strasbourg, avenue Molière, BP 49, 67098 Strasbourg cedex, France; CNRS, Institut de biologie moléculaire et cellulaire, immunopathologie et chimie thérapeutique/Laboratory of Excellence Medalis, université de Strasbourg, 67098 Strasbourg, France.
authors.forename: Jacques Eric
authors.initials: JE
authors.lastname: Gottenberg
authors.affiliation: Rheumatology Department and IPROS, Orleans Hospital, 14, avenue de l'Hôpital, CS 86706, 45067 Orleans cedex 2, France; EA4708 Orleans University, 45067 Orleans cedex 2, France. Electronic address: carine.salliot@chr-orleans.fr.
authors.forename: Carine
authors.initials: C
authors.lastname: Salliot
mesh_terms: D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000628:therapy*; D001688:Biological Products / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D061214:Patient Safety; D012042:Registries
chemical_list: D018501:Antirheumatic Agents; D001688:Biological Products
keywords: Biotherapies; Meta-analyses; Registers; Rheumatoid arthritis; Safety