The effects of leflunomide on clinical parameters and serum levels of IL-6, IL-10, MMP-1 and MMP-3 in patients with resistant rheumatoid arthritis.
OBJECTIVE
The purpose of this open pilot study was to assess possible mechanisms of the effects of leflunomide by studying the influence of the drug on the serum levels of MMP-1, MMP-3, IL-10, IL-6 and their possible correlation with clinical disease parameters.


METHODS
Thirty patients with long standing active rheumatoid arthritis were enrolled in this study. All patients failed at least 5 DMARDs in the past and were on stable treatment for at least 3 months before starting the protocol. The patients received a loading dose of 100 mg for 3 days followed by 20 mg/day thereafter and followed up monthly for 6 months. Disease activity was assessed at baseline, 2 weeks, and every month of therapy thereafter using the following variables: tender joint count, swollen joint count, morning stiffness duration, pain, tiredness, physician's and patient's global assessment, using VAS, ESR and CRP. Clinical effects of the treatment regimen were calculated using the American College of Rheumatology (ACR) criteria for clinical response. Adverse events were recorded. Serum levels of MMP-1, MMP-3, IL-10 and IL-6 were measured before and 3 months after starting the protocol.


RESULTS
Except for tiredness, a statistically significant improvement in all clinical and laboratory parameters of disease activity was reached after 3 months. At this time point the ACR-20 response rate was 46.2%. The levels of MMP-1, MMP-3, IL-6 and IL-10 decreased significantly after 3 months. A statistically significant correlation between serum levels of MMP-1, IL-10 and IL-6 and clinical and laboratory parameters was also shown. After 6 months, 16 out of 30 patients withdrew from the study [adverse events (35.4%), lack of efficacy (9.7%), and low compliance (6.4%)].


CONCLUSIONS
Leflunomide was clinically efficacious in this group of long standing resistant RA in an open study "real life" design. These results comply with those reported in previous clinical trials. Serum MMP-1, MMP-3, IL-10 and IL-6 levels decreased significantly. Despite high withdrawal rate, no serious adverse effects were recorded.
Department of Rheumatology, Sourasky Medical Center, and Sackler, Faculty of Medicine, University of Tel Aviv, 6 Weizman Street, Tel Aviv 64239, Israel. litinskyira@yahoo.com
Irena
I
Litinsky
Daphna
D
Paran
David
D
Levartovsky
Irena
I
Wigler
Ilana
I
Kaufman
Ilana
I
Yaron
Michael
M
Yaron
Dan
D
Caspi
Ori
O
Elkayam
D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000097:blood*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D007555:Isoxazoles / Q000494:pharmacology*; D000077339:Leflunomide; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood*; D019278:Matrix Metalloproteinase 3 / Q000097:blood*; D008875:Middle Aged
D018501:Antirheumatic Agents; D015850:Interleukin-6; D007555:Isoxazoles; D016753:Interleukin-10; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1; D000077339:Leflunomide