Clinical trials in Li En

The data provided in this section are from four randomized controlled clinical trials for adult patients with rheumatoid arthritis and four clinical trials for adult patients with ankylosing spondylitis. [u] Adult rheumatoid arthritis [/u] A randomized, double-blind, placebo-controlled study evaluated the efficacy of etanercept. This study evaluated 234 patients with active rheumatoid arthritis who were unresponsive to at least one but not more than four anti-rheumatic drugs (DMARD) and received 10mg or 25mg etanercept or placebo twice a week for six months. According to the response standard of American Rheumatology Association (ACR), the results of this controlled trial are expressed as the percentage of improvement of rheumatoid arthritis. At the 3rd and 6th month of treatment, the ACR20 and ACR50 responses of patients treated with etanercept were higher than those of placebo control group (ACR20 of etanercept at 3rd and 6th month were 62% and 59% respectively, ACR20 of placebo was 23% and 1 1% respectively, and ACR50 of etanercept was 0. ACR20 and ACR50 responses of etanercept and placebo were compared at all time points (p[0.0 1]. About 15% of patients treated with etanercept reached ACR70 at 3 months and 6 months, while less than 5% of patients treated with placebo. In the patients treated with etanercept, the clinical efficacy usually appears within 1-2 weeks after the start of treatment, and basically always appears within 3 months. The trial showed a dose-effect relationship, and the efficacy of 10mg was between placebo and 25mg. All the indexes of etanercept in ACR standard and other RA indexes not related to ACR, such as morning stiffness, are obviously better than placebo. In the experiment, the Health Assessment Questionnaire (HAQ) was conducted every three months to evaluate the sub-items including disability, vitality, mental health, general health and arthritis. Compared with the placebo group, patients treated with etanercept improved all the sub-items of HAQ at the third and sixth months. After stopping etanercept, arthritis symptoms usually reappear within one month. After 24 months of drug withdrawal, etanercept was used again. According to the results of open research, these patients can achieve the same clinical effect as those who have not stopped taking drugs. In the patients who received the open extended treatment of etanercept continuous treatment, the continuous curative effect of 10 year has been observed. The efficacy of etanercept and methotrexate was compared in a randomized, active drug-controlled study, which was conducted in 632 adult patients with active rheumatoid arthritis who had never received methotrexate treatment (course of disease [3 years]), with blind imaging evaluation as the main end point. 10mg or 25mg etanercept was injected subcutaneously twice a week for 24 months, and the dose of methotrexate was gradually increased from 7.5mg per week to 20mg per week for 24 months in the first 8 weeks of the trial. The clinical improvement effect of 25mg etanercept group, including active seizure, was the same as that of the previous trial within 2 weeks of treatment and lasted for 24 months. Before medication, the patient was moderately disabled, and the average HAQ value was 1.4 to 1.5. After 25mg etanercept treatment 12 months, the HAQ of about 44% patients reached the normal value (less than 0.5). This effect can be maintained until the second year of the study. In this study, the damage of joint structure was evaluated by imaging, which was expressed by the changes of Sharp Total Score (TSS) and its components, namely erosion score and joint space stenosis (JSN) score. Radiographic images of hands/wrists and feet at baseline, 6th month,12nd month and 24th month were obtained. The effect of 10mg etanercept on joint structure injury is always lower than that of 25mg etanercept. The erosion score of 25mg etanercept in 12 months and 24 months was significantly better than that of methotrexate. There was no significant difference in TSS and JSN scores between methotrexate and 25mg etanercept. The results are as follows. Radiological changes: comparison of etanercept and methotrexate in RA patients (course of disease [3 years]) In another randomized double-blind active control trial, etanercept alone (25mg twice a week) and methotrexate alone (7.5-20 times) were compared in 682 adult patients with rheumatoid arthritis (course of disease ranged from 6 months to 20 years, with an average of 5 years, except MTX). Compared with etanercept alone or methotrexate alone, the proportion of patients who reached ACR20, ACR50 and ACR70 at the 24th and 52nd weeks in etanercept/methotrexate combined treatment group, as well as DAS and HAQ scores, were significantly improved (see the table below for details). After 24 months of treatment, compared with etanercept alone or methotrexate alone, the advantages of etanercept/methotrexate combination are also significant. Results: Compared with the RA patients treated with etanercept, methotrexate and etanercept combined with methotrexate 12 months, and the course of disease ranged from 6 months to 20 years, the radiotherapy progress of etanercept monotherapy was less than that of MTX monotherapy. Compared with etanercept group or MTX alone, the radiation phase progress of etanercept /MTX combination has been significantly improved (see the figure below). Radiological progress: Compared with etanercept, methotrexate and etanercept/methotrexate in the treatment of RA patients with a course of 6 months to 20 years (Results 12 months), after 24 months of treatment, compared with etanercept group or MTX alone, the radiation progress after the combined treatment of etanercept /MTX also improved significantly. Similarly, etanercept monotherapy is superior to MTX monotherapy. In one analysis, patients who fell for any reason during the trial were considered to be in progress. Compared with etanercept or methotrexate alone for 24 months, the proportion of patients with no progress (TSS change ≤0.5) after etanercept combined with methotrexate is higher (62%, 50% and 36% respectively; There was significant difference between etanercept and methotrexate alone (p[0.05]). Among the patients who completed all 24 months of treatment in the trial, the progression-free rates were 78%, 70% and 6 1%, respectively. A double-blind, placebo-controlled clinical study of 420 patients with active RA evaluated the safety and efficacy of 50mg etanercept (25mg×2, subcutaneous injection) once a week. In this study, 53 subjects took placebo, 2 14 subjects took 50mg etanercept 1 time, and 153 subjects took 25mg etanercept twice a week. In the eighth week, the two etanercept treatment schemes were equally safe and effective in improving the indications and symptoms of RA. The data of 16 weeks does not show that the two treatment schemes are comparable (not inferior). [u] Adult ankylosing spondylitis [/u] In three randomized double-blind studies, the efficacy of etanercept in the treatment of ankylosing spondylitis was evaluated. The regimen is to give etanercept 25mg or placebo twice a week. A total of 4,065,438+0 patients participated in the trial, of which 203 patients were treated with etanercept. In the largest of the three trials, the patient is between 65438 08 and 70 years old (n=277) and has active ankylosing spondylitis, which is defined as: the visual analogue scale (VAS) of the average duration and severity of morning stiffness should be ≥30, and the VAS scores of two of the following three other indicators should be ≥30: overall evaluation of the patient and night pain. During the study, patients receiving DMARDs, NSAIDs or corticosteroids can continue to use a stable dose of these drugs. Patients with complete spinal stiffness were excluded from the experiment. 138 patients received subcutaneous injection of 25 mg etanercept or placebo twice a week for 6 months (the dose setting was determined according to the dose groping test of RA patients). The main treatment index is that at least three of the four indexes (including overall evaluation of patients, back pain, basic symptoms and inflammation) have improved by ≥20%(ASAS 20), and the rest indexes have not deteriorated. ASAS 50 and 70 respondents applied the same standard, that is, 50% improvement or 70% improvement respectively. Compared with placebo, the ASAS20, ASAS50 and ASAS 70 of patients treated with etanercept improved significantly two weeks after the start of treatment. The response of patients with ankylosing spondylitis in placebo-controlled trials showed clinical response at the first visit (the second week) and remained unchanged during the 6-month treatment period. The clinical efficacy of patients receiving drug combination therapy at baseline is similar to that of patients not receiving drug combination therapy. Similar results were obtained in two smaller ankylosing spondylitis trials. In the fourth double-blind, placebo-controlled trial, 356 patients with active ankylosing spondylitis were included, and the safety and efficacy of subcutaneous injection of 50mg(25×2) per week and 25mg twice a week were evaluated. The safety and efficacy of 50mg 1 once a week and 25mg twice a week are similar. 【 Domestic Clinical Trials 】 Two registered clinical trials were conducted in China, aiming at active rheumatoid arthritis (RA) and ankylosing spondylitis (AS). The first clinical trial was a 24-week randomized, multicenter, placebo-controlled study to evaluate the efficacy and safety of etanercept in patients with active rheumatoid arthritis (RA) who failed to respond to methotrexate in China (0881a1-319-cn). This study compared the efficacy and safety of once-weekly subcutaneous injection of 50mg etanercept with placebo in RA patients treated with methotrexate (MTX), including 12 weeks double-blind treatment and 12 weeks safety open study. In the double-blind period, 156 patients were enrolled, including 77 patients in etanercept +MTX group and 79 patients in placebo +MTX group. *** 149 subjects completed double-blind treatment and 146 patients completed open treatment. After treatment 12 weeks, 62.3%(48/77 cases) of subjects in etanercept +MTX group reached ACR20 (the main end point), and its confidence interval was [5 1.5~73.2%], which was higher than that in placebo +MTX group (22.8%). At the 4th week after administration, the ratio difference between the two groups was 23%, and its 95% confidence interval was [9~36%]. This result is significant, indicating that etanercept +MTX takes effect quickly and significantly improves RA compared with placebo +MTX. After more than 24 weeks of administration, the safety and drug resistance of etanercept +MTX were consistent with previous global clinical studies. The other is a randomized, double-blind, multicenter, placebo-controlled clinical study of ankylosing spondylitis (AS) in China, 12 weeks, including 6 weeks of double-blind treatment and 6 weeks of open treatment (088 1A 1-322-CN). During the double-blind treatment, subjects were randomly given 50 mg etanercept or placebo once a week. * * * 152 subjects, including 74 cases in etanercept group and 78 cases in placebo group; 147 subjects completed the open treatment. After 6 weeks of treatment, 86.5%(64/74 cases) of the subjects in etanercept group reached ASAS20[ main end point], with 95% confidence interval [78.7~94.3%], which was 57% higher than that in placebo group, and the 95% confidence interval of the proportion difference was [44.2~69.8%]. In the second week after administration, the difference in the proportion of patients who received response between the two groups was 45.3%, and the confidence interval was 95%. It is significant, indicating that etanercept takes effect quickly and obviously improves ankylosing spondylitis compared with placebo. Etanercept +MTX was administered 12 weeks, which proved that the safety and drug resistance of etanercept +MTX were consistent with the results of global clinical research.