title: Efficacy and safety of leflunomide in DMARD-naive patients with early rheumatoid arthritis: comparison of a loading and a fixed-dose regimen.
abstract: OBJECTIVE
  To assess the efficacy of LEF administered with or without a loading dose in DMARD-naïve patients with early RA.
  
  
  METHODS
  This multicentre, double-blind, randomized clinical trial included adults with RA diagnosed within 6 months (ACR criteria). Patients were randomly selected to receive either a 100 mg loading dose or a 20 mg fixed dose of LEF for 3 days, followed by a 3-month open-label maintenance period of 20 mg LEF qd. The primary outcome criterion was ACR20 response rate at study end in the intent-to-treat population. Secondary criteria were ACR20, ACR50, ACR70 and DAS28 response rates at 1 and 3 months and safety.
  
  
  RESULTS
  The intent-to-treat population included 120 patients (median time since diagnosis 0.95 months). The ACR20 response rate at study end was 69.0% (95%CI 60.5%, 77.4%). Response rates were significantly lower (P = 0.025) in the loading-dose group [58.5% (45.2%, 71.8%)] than in the fixed-dose group [77.8% (67.5%, 88.0%)]. Three-month ACR50, ACR70 and DAS28 response rates were 41.4%, 17.7% and 81.7%, respectively, with no significant differences between groups. Adverse events occurred in 53.7% (loading-dose group) and 49.3% (fixed-dose group) of patients, most frequently diarrhoea and elevated hepatic enzymes; these occurred more frequently and earlier in treatment when the loading dose was used.
  
  
  CONCLUSIONS
  LEF was effective in DMARD-naïve patients with early disease. No incremental benefit was observed with the use of a loading dose, which may be associated with an increased initial rate of adverse events. The advantage of LEF initiation with a loading dose is not confirmed in this population.
  
  
  BACKGROUND
  ClinicalTrials.gov, http://clinicaltrials.gov/, NCT00596206.
authors: Research Laboratory and Academic Unit of Clinical Rheumatology, Department of Internal Medicine, University of Genova, Italy. mcutolo@unige.it
authors: Maurizio
authors: M
authors: Cutolo
authors: Horatiu
authors: H
authors: Bolosiu
authors: Gilles
authors: G
authors: Perdriset
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077339:Leflunomide; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D007555:Isoxazoles; D000077339:Leflunomide
keywords: early rheumatoid arthritis; efficacy; leflunomide; loading dose; safety