Effect Of Combination Methotrexate Or Leflunomide With Cyclophosphamide On IL-6and RANKL In Patients With Rheumatoid Arthritis

BackgroundRheumatoid arthritis is a kind of systematic autoimmune disease that characterized by destructive arthritis. Some studies show that IL-6regarded as an inflammatory cytokine has closest ligament with the pathogenesis and disease reactiveness of rheumatoid arthritis. Meanwhile, it directly raises RANKL which can destroy the joints through inducing the generation of osteoclast. Based on the theory of cell cycle power mechanics, we intermittently use small dose of methotrexate or leflunomide combined with cyclophosphamide to treat RA patients and have acquired satisfactory curative effects. In order to prove the principle, we design this subject to get a clear idea about the relationship between IL-6、RANKL and rheumatoid arthritis. At the same time to clarify the concrete mechanism of setting back joint destruction by using combining treatment.ObjectiveWe observe the disease reactiveness of rheumatoid arthritis, grade of X-ray,and the level of IL-6and RANKL, in order to prove the relationship between IL-6、 RANKL and disease reactiveness of rheumatoid arthritis and joint destruction. Meanwhile, to compare the results of each groups and clarify the mechanism of combining treatment.Method1. Chose37patients with rheumatoid arthritis whose disease is reactive as experimental groups. At the same time,9healthy persons as health control group. 2. The experimental groups are divided into two groups:MTX group and LEF group. All the patients take medicine for12weeks. The patients whose DAS28scores are less than2.6continue to take the same medicine. While the patients whose DAS28scores are more than2.6begin to take MTX/LEF combined CTX or MTX combined LEF for anther12weeks.3.Collect clinical data of all the patients at0、12and24weeks, including the swollen joint count, the tender joint count, the time of morning stiffness, blood sedimentation, C-reactive protein, DAS28, and the Sharp score. Gather peripheral blood, detect IL-6and RANKL using ELISA.Result1. Compared with health control group, the IL-6and RANKL levels of patients with rheumatoid arthritis are significantly higher than normal.2. The comparison of the four experimental groups:1) At24weeks, DAS28scores are lower than the baseline value for each of the experimental group (P<0.05);2) At24weeks, the Sharp scores of all the four groups are not increased significantly (P>0.05).3) At24weeks, the levels of IL-6is lower than the baseline value (P<0.05). MTX/LEF combined CTX group is lower than the MTX combined LEF group, but there is no significant statistical difference (P>0.05).4) At24weeks, the levels of RANKL is lower than the baseline value (P<0.05). MTX/LEF combined CTX group is lower than the MTX combined LEF group, but there is no significant statistical difference (P>0.05).3.Relevance analysis of the IL-6,RANKL level with ESR、DAS28and Sharp score: 1) IL-6is positive-correlated with ESR and DAS28.(P<0.01)2) RANKL is not distinctly positive-correlated with Sharp score.(P>0.05)3) IL-6is positive-correlated with RANKL.(P<0.01)Conclusion1.IL-6can predict the disease reactiveness of rheumatoid arthritis.2..Combination therapy can treat the intractable rheumatoid arthritis.