Efficacy and safety of leflunomide in DMARD-naive patients with early rheumatoid arthritis: comparison of a loading and a fixed-dose regimen

作者：Cutolo Maurizio^*; Bolosiu Horatiu; Perdriset Gilles

来源：Rheumatology, 2013, 52(6): 1132-1140.

DOI：10.1093/rheumatology/kes321

• early rheumatoid arthritis
• leflunomide
• loading dose
• efficacy
• safety

Objective. To assess the efficacy of LEF administered with or without a loading dose in DMARD-naive patients with early RA. %26lt;br%26gt;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. %26lt;br%26gt;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. %26lt;br%26gt;Conclusion. LEF was effective in DMARD-naive 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. %26lt;br%26gt;Trial Registration. ClinicalTrials.gov, ext-link-type=%26quot;uri%26quot; xlink:href=%26quot;http://clinicaltrials.gov/%26quot; xmlns:xlink=%26quot;http://www.w3.org/1999/xlink%26quot;%26gt;http://clinicaltrials.gov/, NCT00596206.

• 出版日期2013-6