Leflunomide (LEF) is a new disease-modifying drug for the treatment of rheumatoid arthritis (RA), which has been reported in the literature [1] to have good therapeutic effects in rheumatoid arthritis, and methotrexate (MTX) is recognized as the “gold standard” drug for the treatment of RA. methotrexate (MTX) is recognized as the “gold standard” drug for the treatment of RA. The purpose of this study was to observe the efficacy and adverse effects of the combination of the two drugs and leflunomide alone, and the results are summarized below. Data and methods Experimental design The trial was a controlled trial, with the test group being the LEF+MTX group and the control group being the LEF group alone. the test and control groups were randomly divided 1:1 into the LEF+MTX group and the LEF group for 24 wk. each group was followed up before treatment and 2, 4, 8, 12, 16, 20, and 24 wk after taking the drug. Patient selection All 60 patients were diagnosed with active rheumatoid arthritis according to the 1987 American College of Rheumatology (ACR) diagnostic criteria, aged 18 to 65a. Patients with (1) heart, liver, kidney, or gastrointestinal diseases, (2) pregnant or lactating women or patients who intend to have children in the near future, (3) allergic or hypersensitive to the test drug, (4) patients with pre-test drug allergies, and (5) patients with a history of hypersensitivity. (3) patients with allergy or hypersensitivity to the test drug, (4) patients taking immunosuppressive therapy within 1mo before the test. General conditions A total of 60 patients entered the trial, 30 in the test group and 30 in the control group. The indexes of patients in the two groups at the time of trial entry were basically the same, see Table 1. Examination items and methods Liver and renal function, routine blood, urine, fecal occult blood, sedimentation (ESR), C-reactive protein (CRP) and rheumatoid factor (RF) tests were performed before the trial and 12 and 24 wk after taking the drug, and chest X-ray and electrocardiogram were performed before and after the treatment course. Chest X-ray and electrocardiogram. The abnormal laboratory indicators were also judged in relation to the drugs. Rest pain, morning stiffness, number of swollen joints (SJC), number of tender joints (TJC), grip strength, joint function, ability to perform daily living, physician evaluation, and patient evaluation were recorded. The ability of daily living had 24 indicators to assess such as dressing, standing, eating, drinking, and walking. Rating 4 levels: 0=no difficulty; 1=some difficulty; 2=very difficult; 3=unable to perform. Rest pain, patient and physician evaluations were calculated on a visual analog scale method 10-point scale. Dosing The test group received LEF 10 mg orally once daily and MTX 7.5 mg once a week; the control group received LEF 20 mg once daily. The patients in both groups were given a loading dose of LEF 50mg qd-1 in the first 3 d. All groups were allowed to take NSAIDs at the same time. Efficacy evaluation The following indexes were evaluated before and 12 and 24 wk after treatment: rest pain, morning stiffness, SJC, TJC, grip strength, joint function, ability to perform daily activities, physician evaluation, patient evaluation, ESR, CRP and RF, and the effective rate of each index was calculated [(pre-treatment value – post-treatment value)/pre-treatment value × 100%], and the mean of the improvement rate of the above indexes The average of the improvement rate of the above indicators was the overall effective rate. Efficacy evaluation criteria: ineffective – improvement of clinical symptoms, signs and laboratory tests <30%; improved - improvement of clinical symptoms, signs and laboratory tests between 30% and 49% (including 30%); progress - improvement of clinical symptoms, signs and laboratory tests between 30% and 49% (including 30%); improvement of clinical symptoms, signs and laboratory tests between 30% and 49% (including 30%) -Improvement - improvement in clinical symptoms, signs and laboratory tests between 50% and 75% (including 75%); Significant progress - improvement in clinical symptoms, signs and laboratory tests >75%. Total effective rate = (improvement + progress + significant progress) number of cases / total number of cases × 100%. Adverse reactions The patient’s possible discomfort should be observed and recorded at each visit or follow-up after drug administration, and its degree should be judged according to mild, moderate, severe and life-threatening, and the relationship between adverse reactions and the tested drugs should be analyzed. After the occurrence of adverse reactions, the regression of adverse reactions should be observed at regular follow-up visits. Statistical treatment indicates mean ± standard deviation. Ridit analysis was used for comparison of efficacy. c2 test was used for comparison of incidence of adverse reactions and counting data, and t test was used for comparison of measurement data. p < 0.05 was considered a significant difference. Results Changes in clinical and laboratory indexes of the groups before and after treatment After 12 and 24 wk of treatment in the 2 groups, there were significant improvements in TJC, SJC, rest pain, ability to perform daily living, physician evaluation, patient evaluation, ESR, CRP and RF, P < 0.01. The test group was slightly better than the control group, but not statistically significant, P > 0.05, see Table 2. Comparison of group efficacy After 2 wk of treatment, the test The total effective rate was 89% (24/27) in the test group and 61% (17/28) in the control group, and the difference between the two groups was significant, P < 0.05; the difference between the total effective rate of the two groups was not significant after 12 wk and 24 wk of treatment, P > 0.05, see Table 3. Adverse reactions Eight patients in the test group had adverse reactions, the incidence rate was 27%, including three cases due to nausea, leukopenia However, the rate of gastrointestinal reactions and ALT elevation in the test group was slightly higher than that in the control group. All adverse reactions were recovered during drug discontinuation or continuation of treatment. LEF is a disease-modifying drug for RA [2]. LEF blocks the synthesis of pyrimidines mainly by inhibiting the activity of dihydroorotic acid dehydrogenase (DHODH) [3,4], so that proliferating active cells (such as T lymphocytes and B lymphocytes) are inhibited. MTX inhibits purine synthesis and exerts immunosuppressive effects. Foreign literature reports [5,6] that the 2 drugs have synergistic effects in terms of mechanism of action. In this study, we found that the onset of action of the combination was significantly faster than that of LEF alone, and the efficacy at 12 wk was similar to that of LEF alone, but the adverse effects were slightly higher than those of LEF treatment alone, especially gastrointestinal reactions and elevated liver enzymes. Therefore, the observation of adverse reactions should be paid attention to when the combination is administered. Because of the short duration and small number of cases in this study, a long and large sample trial is needed to further observe the efficacy and adverse effects of the combination of drugs. In addition, because LEF has not been used in our hospital for a long time, we were not able to observe the efficacy of small-dose LEF combined with small-dose MTX in the treatment of RA, which is also a shortcoming of this trial. These are the directions for our next study.