Objective To investigate the clinical effect of methotrexate combined with leflunomide in the treatment of patients with rheumatoid arthritis.Methods 660 patients with rheumatoid arthritis were selected,they were divided into research group and the control group according to the random number method,with 330 cases in each group.The control group was treated with methotrexate alone,while the research group was treated with leflunomide and methotrexate.The clinical effect and adverse reaction of the two groups were compared after 6 months.Results Compared with before treatment,the pain index[(1 .43 ±0.32)vs.(1 .83 ±0.52)],time of morning stiffness [(0.77 ±0.5)h vs.(1 .1 8 ±0.44)h],grip strength[(1 58.65 ±53.45)mmHg vs.(1 33.29 ±44.1 2)mmHg], swelling[(6.81 ±2.32)vs.(9.32 ±2.43)]and the swelling index[(1 .54 ±0.26)vs.(1 .70 ±0.33)]in the two groups after treatment were improved significantly,and the differences were statistically significant(t =3.84,5.24, 3.54,4.05,6.95,4.33,5.22,3.69,2.98,5.64,all P <0.05).And the indices of the research group were significantly better than the control group after treatment,the differences were statistically significant(t =2.36,2.68,3.02,3.22, 2.87,all P <0.05).ESR[(38.56 ±23.67)mm/h vs.(56.78 ±23.45)mm/h],C -reactive protein[(1 2.98 ± 11.89)mg/L vs.(21 .68 ±9.57)mg/L]and rheumatoid factor[(85.67 ±31 .98)IU /mL vs.(1 32.68 ±96.36)IU /mL] of the two groups after treatment were significantly lower than before treatment,in which the indices of the research group were significantly lower than the control group,and the differences were statistically significant(t =3.65,3.02, 4.22,all P <0.05).The disease activities of the research group(32.73%,58.1 8%,83.03%)were significantly better than those of the control group(7.27%,23.64%,34.85%)at 1 ,6,1 2 weeks after treatment,the differences were statistically significant(χ2 =6.35,4.85,5.02,all P <0.05).In addition,the degree of reduction of joint swelling in the research group at three time points was better than the control group,and the differences were statistically significant(all P <0.05 ).The total effective rate of the research group(98.1 8%)was significantly higher than 81 .82% of the control group,the difference was statistically significant(χ2 =8.1 8,P <0.01 ).The adverse reactions such as itching,rash and gastrointestinal discomfort occurred in the two groups,which did no affect the treatment,and no other serious adverse reactions.There was no significant difference in the incidence of adverse reactions between the two groups(χ2 =1 .29,P >0.05).Conclusion Methotrexate combined with leflunomide has good effect in the treatment of patients with rheumatoid arthritis,which can significantly improve clinical symptoms,as well as effectively reduce the related indicators of rheumatoid arthritis in active phase,with good safety,it is worth promoting.