Objective: Explore the efficacy and safety of Guizhi Shaoyao Zhimutang combine methotrexate (MTX) and sulfasalazine (SSZ) on refractory rheumatoid arthritis (RA). Method: Select 81 patients met the inclusion criteria were randomly divided into two groups. Patients in treatment group ( n =40) were treated with Guizhi Shaoyao Zhimutang combine methotrexate (MTX) and sulfasalazine (SSZ). Patients in control group ( n =41) were treated with methotrexate (MTX) and sulfasalazine (SSZ). The therapeutic course was 12 weeks in both groups. Based on American college of rheumatology (ACR) recommended evaluation of RA disease activity core set of indicators to assess the two groups before and after treatment. Result: After treatment

both groups score major indicators of disease activity were significantly decreased

before and after treatment the differences were highly statistically significant (P<0.01)

the treatment group score lower than the control group

the difference was significant (P<0.05 ). The treatment group achieved ACR20

ACR50

ACR90 efficacy criteria were: 37.5%

32.5%

20%

with a total effective rate 90%; the control group achieved ACR20

ACR50

ACR90 efficacy criteria were: 46.34%

19.51%

4.88 %

the total efficiency of 70.73%. Conclusion: Guizhi Shaoyao Zhimutang combine methotrexate (MTX) and sulfasalazine (SSZ) the efficacy of the treatment of refractory rheumatoid arthritis is superior to the efficacy of methotrexate (MTX) and sulfasalazine (SSZ)

and has good security.