title: Dose down-titration of biological DMARDs in patients with rheumatoid arthritis over time and in daily clinical practice.
abstract: OBJECTIVE
  To describe and compare dosing optimisation in biological DMARDs (bDMARDs) and relapses after that, in a cohort of rheumatoid arthritis (RA) during clinical practice.
  
  
  METHODS
  Observational retrospective longitudinal study of RA patients taking bDMARDs from December 1999 to November 2013. Optimisation was defined as a 15% decrease in dose either reducing single dose or separating dose interval administration, for at least 4 times the recommended period between dosages. Relapse was defined as suspension or starting again with the recommended dose after optimisation. Incidence rates (IR) per 100 patient-years were estimated using survival techniques. Cox multivariate models were conducted to compare bDMARDs expressed in hazard ratios (HR) and confidence intervals [95%CI].
  
  
  RESULTS
  443 patients and 752 different courses of bDMARDs treatments were included. We observed 146 optimisations with an IR of 8.1. The HR of optimisation in: a) adalimumab, etanercept and rituximab compared to infliximab was 1.56 [1.01-2.4], 1.5 [0.9-2.4] and 0.6 [0.3-1.4], respectively; b) adalimumab, etanercept compared to rituximab were 2.3 [1.2-4.5] and 2.2 [1.2-4.3]. There were no statistically significant differences between adalimumab and etanercept. Following optimisation, 36% relapsed (78% due to disease activity). The IR related to disease activity was 6.3, and was lower for adalimumab and etanercept compared to infliximab (HR: 0.42; [0.19-0.94]; HR: 0.34; [0.13-0.89], respectively). There were no statistically significant differences between etanercept and adalimumab. No patients on rituximab relapsed.
  
  
  CONCLUSIONS
  Optimisation was similar between adalimumab and etanercept, and was lower for infliximab and rituximab. After optimisation, rituximab did not relapse, but infliximab did with the highest hazard.
authors.affiliation: Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IDISSC), Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Rodriguez-Rodriguez
authors.affiliation: Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IDISSC), Hospital Clínico San Carlos, Madrid; and Universidad Camilo José Cela, Madrid, Spain. 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, Madrid, Spain.
authors.forename: Jose Ramón
authors.initials: JR
authors.lastname: Lamas
authors.affiliation: Rheumatology Unit, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Gomez
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: Margarita
authors.initials: M
authors.lastname: Blanco
authors.affiliation: Rheumatology Unit, Hospital Clínico San Carlos, Madrid; and Medicine Department, Universidad Complutense, Madrid, Spain.
authors.forename: Juan Angel
authors.initials: JA
authors.lastname: Jover
authors.affiliation: Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IDISSC), Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Lydia
authors.initials: L
authors.lastname: Abasolo
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy*; D001688:Biological Products / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D012008:Recurrence; D012074:Remission Induction; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D001688:Biological Products