title: Safety of disease-modifying antirheumatic drugs and biologic agents for rheumatoid arthritis patients in real-life conditions.
abstract: OBJECTIVE
  The aim of this study was to describe the incidence rate (IR) of adverse drug reactions (ADRs) in daily clinical practice, related to disease-modifying antirheumatic drugs (DMARDs) and biologic agents (BA) in rheumatoid arthritis (RA) patients, and to analyze factors causing discontinuation due to ADRs.
  
  
  METHODS
  This was a prospective observational study (October 2010 to October 2011). RA patients who were attended in our hospital taking DMARDs or BA during the study period were included. ADRs were injuries related to these drugs and registered with a software system in routine visits. ADRs could be mild (lowering dosage), moderate (drug discontinuation), or severe (hospital admission). The IR of ADR per 100 patient-years was estimated using survival techniques. Cox regression models (HR; 95% confidence interval) were used to explore factors associated with discontinuation due to ADRs.
  
  
  RESULTS
  In total, 1202 patients were analyzed, with 158 ADRs (IR = 15.2). Of all ADRs, 80.4% required drug discontinuation (IR = 12.2). Age, less disease and therapy duration, taking corticoids, and combined therapy versus monotherapy (HR = 3; 95% CI: 2.0-4.4) were the factors independently associated to discontinuation due to ADRs. We did not find statistical differences between the different monotherapy regimens. Regarding combinations, Methotrexate + BA had the lowest risk of discontinuation compared to the rest (HR = 0.24; 95% CI: 0.09-0.6).
  
  
  CONCLUSIONS
  We have estimated the incidence of ADRs related to DMARDs/BA in real-life conditions. We confirm the role of combined therapy in the development of discontinuations due to ADRs, except for BA + MTX, which did not show an increase of toxicity compared to monotherapy. This combination seems to be safer than others.
authors.affiliation: Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IDISSC), Hospital Clínico San Carlos, Calle Martín Lagos, s/n, 28034 Madrid, Spain.
authors.forename: Lydia
authors.initials: L
authors.lastname: Abasolo
authors.affiliation: Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IDISSC), Hospital Clínico San Carlos, Calle Martín Lagos, s/n, 28034 Madrid, Spain; Universidad Camilo José Cela, Madrid, Spain. Electronic address: lleon.hcsc@salud.madrid.org.
authors.forename: Leticia
authors.initials: L
authors.lastname: Leon
authors.affiliation: Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IDISSC), Hospital Clínico San Carlos, Calle Martín Lagos, s/n, 28034 Madrid, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Rodriguez-Rodriguez
authors.affiliation: Consejo Superior de Investigaciones Científicas, Barcelona, Spain.
authors.forename: Aurelio
authors.initials: A
authors.lastname: Tobias
authors.affiliation: Rheumatology Unit, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Zulema
authors.initials: Z
authors.lastname: Rosales
authors.affiliation: Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IDISSC), Hospital Clínico San Carlos, Calle Martín Lagos, s/n, 28034 Madrid, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Maria Leal
authors.affiliation: Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IDISSC), Hospital Clínico San Carlos, Calle Martín Lagos, s/n, 28034 Madrid, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Castaño
authors.affiliation: Rheumatology Unit, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Vadillo
authors.affiliation: Rheumatology Unit, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Macarron
authors.affiliation: Rheumatology Unit, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Fontsere
authors.affiliation: Rheumatology Unit, Hospital Clínico San Carlos, Madrid, Spain; Medicine Department, Universidad Complutense, Madrid, Spain.
authors.forename: Juan Angel
authors.initials: JA
authors.lastname: Jover
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001688:Biological Products / Q000009:adverse effects* / Q000627:therapeutic use; D016208:Databases, Factual; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D001688:Biological Products; D008727:Methotrexate
keywords: Adverse drug reactions; Biological agents; Disease-modifying antirheumatic drugs; Incidence rates; Rheumatoid arthritis