Leflunomide monotherapy in patients with early rheumatoid arthritis: Results of the Russian national Arava mono study

Abstract

The treatment of early rheumatoid arthritis (RA) is usually started using one of the synthetic disease-modifying antirheumatic drugs. The choice of these drugs is very limited and leflunomide (LEF) is one of the most promising agents. The present study assessed the results of using the standard LEF regimen for patients with early RA in the everyday clinical practice of Russian health care facilities. Subjects and methods. The study enrolled the patients followed up in 20 medical centers of the Russian Federation in May 2008 to January 2010. The RA patients who met the 1987 American College of Rheumatology (ACR) classification criteria, had a less than 2-year history of the disease, and had not received LEF before were included. All the patients were above 18 years of age and they signed an informed consent form. The physicians were recommended to give the drug in a dose of 100 mg/day for the first 3 days, then 20 mg/day continuously. If adverse reactions occurred, the dose might be reduced to 10 mg/day. The patients were examined before and 12, 24, 36, and 48 weeks after LEF therapy. The efficiency of the treatment was evaluated by the European League Against Rheumatism (EULAR) classification criteria using DAS 28 scores, by the ACR criteria, and functional changes using HAQ scores and quality of life using the EQ-5D questionnaire. Results. The study included 484 patients with RA. Its diagnosis corresponded to the 1987 ACR criteria. There were 80 men and 404 women in this group. The patients’ mean age was 48.1±13.4 years; the mean duration of the disease at its onset was 14.1±12.8 months. A significant decrease in the number of patients with high DAS 28 scores was recorded every 12 weeks during the treatment. It reduced from 355 (73.3%) to 41 (8.5%) by the end of the observation. At the same time, there was a significant increase in the number of patients with low activity and remission every 12 weeks (p < 0.01). During the last visit, a remission was recorded in 57 (11.8%) patients and low disease activity in 59 (12.2%) patients. Twelve weeks after initiation of treatment, 210 (43.4%) patients achieved a significant improvement according to the EULAR criteria. During a subsequent follow-up, the number of patients with a considerable improvement increased statistically significantly every 12 weeks and there were 373 (77%) patients by the end of the follow-up. Efficiency evaluation showed a 20% response according to the ACR criteria in 154 (31.8%) patients after the first 12 weeks. There was a significant rise in the number of patients with a 20% ACR improvement within the first 36 weeks of the follow-up and there were 323 (66.7%) patients following 48 weeks. The number of patients with 50% and 70% ACR responses considerably increased throughout the observation (p < 0.01). After 48-week treatment, 141 (29%) and 38 (8%) patients showed 50% and 70% ACR responses, respectively. The therapy significantly improved quality of life, as estimated by EQ-5D questionnaire, and resulted in a considerable functional improvement according to HAQ scores. ARs were seen in 51 (10.5%) patients during the study. At the follow-up, LEF was discontinued in 58 patients, including 23 (4.8%) because of its inefficiency, in 9 (1.9%) due to ARs, and in 26 (5.4%) for other reasons. The efficiency of the therapy and the rate and causes of its withdrawal were comparable in the patients receiving LEF in accordance with the standard regimen using its saturating dose in the first 3 days and in those who did not take the saturating dose. Conclusion. The standard treatment regimen of LEF using its high doses in the first 3 treatment days in patients with early RA enables the inflammatory activity to be effectively inhibited and does not cause any substantial increase in the frequency of ARs.