Leflunomide combined with methotrexate in treatment of rheumatoid arthritis / 中国新药与临床杂志

AIM: To investigate the efficacy and safety of low-dose leflunomide (Lef) combined with methotrexate (MTX) in the treatment of rheumatoid arthritis (RA). METHODS: Sixty-four RA patients were randomly divided into two groups, with 32 patients in each group. All the patients were required to stop the treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) for 1 wk before entering the trial. Patients in the Lef+MTX group received Lef 20 mg, po, qd in the first 4 wk, followed by 10 mg,po, qd for next 20 wk. Patients also received MTX 7.5 mg,po, qw during the trial. Patients in the MTX group received MTX 15 mg,po, qw for 24 wk. Physical and laboratory examinations were performed at the beginning of the trial, after 12 wk treatment and 24 wk treatment. Entopic X-ray examination of both hands was performed before and after the treatment. RESULTS: The rate of remarkable improvement was 88% (28/32) in Lef+MTX group and 38% in MTX group (12/32). Adverse reactions were reported in 12% (4/32) patients in Lef+MTX group and 43% (14/32) patients in MTX group. The reported adverse reactions were rash and nausea in Lef+MTX group and nausea, vomiting, oral ulcer, alopecia, ALT elevation, palpitation and menoxenia in MTX group. CONCLUSION: Combination of Lef with MTX is safe and effective in treatment of RA with less adverse reactions.

Leflunomide, a new disease-modifying drug for treating active rheumatoid arthritis in methotrexate-controlled phase II clinical trial / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of leflunomide in comparison with methotrexate (MTX) on patients with rheumatoid arthritis (RA) in China.</p><p><b>METHODS</b>Five hundred and sixty-six patients with active rheumatoid arthritis were randomly assigned to receive leflunomide at 20 mg once daily or MTX at 15 mg once weekly in a controlled trial. Five hundred and four patients completed the 12-week treatment and some patients continued the treatment for 24 weeks.</p><p><b>RESULTS</b>Both leflunomide and MTX could improve the symptoms, signs, and joint function, but there were no changes in X-ray observations of patients with rheumatoid arthritis. In the leflunomide group, the overall rates of effectiveness at 12 weeks and 24 weeks were 86.94% and 92.31% respectively; the rates of remarkable improvement were 64.95% and 79.81% respectively. In the MTX group, the overall rates of effectiveness at 12 weeks and 24 weeks were 84.04% and 83.15% respectively; the rates of remarkable improvement were 56.81% and 75.28% respectively. According to intent-to-treat analysis, the ACR 20% response rates at 12 weeks and 24 weeks in the leflunomide group were 62.54% and 67.18% respectively, compared with 60.08% and 61.32% respectively in MTX group. No statistical differences were shown in the efficacy between the two groups (P > 0.05). The adverse events in the leflunomide group were gastrointestinal symptoms, skin rash, alopecia, nervous system symptoms, decreased leukocyte count, and elevation of alanine aminotransferase (ALT). Most of these side effects were mild and transient. The incidence of adverse events in the leflunomide group was 16.84%, significantly lower than that in MTX group (28.17%, P = 0.002).</p><p><b>CONCLUSIONS</b>Leflunomide is effective in the treatment of RA with less adverse events than MTX. Its efficacy is similar to MTX, but the incidence of adverse events and the rate of withdrawal due to adverse events were lower in the leflunomide group than in MTX group.</p>

Leflunomide in treatment of rheumatoid arthritis——a long-term follow up / 中国新药与临床杂志

AIM: To investigate the efficacy and safety of leflunomide (Lef) in long-term treatm ent of rheumatoid arthritis (RA).　METHODS: Twenty-one patients ［M 2,F 19; age (45±s 9)a］ with RA were s elected. Disease duration was (59±48) mo. All patients enrolled in double-blin d or single-blind trials with Lef 20 mg, po, qd for 6 mo at first. Doses of leflunomide in nine patients were reduced down to 10 mg, qd and all the others c ontinued the treatment with Lef at 20 mg, qd. 　RESULTS: All twenty-one patient s we re followed up for 1.5 a. The results showed that twenty patients had remarkable improvement and one patient had clinical remission. Ni neteen patients had been followed up for more than 2 a and twelve patients had r emarkable improvement while seven patients had clinical remission. Twelve pati ents had been followed up for 3 a and three of them had remarkable improvement while nine patients had clinical remission. Total rate of adverse reactions was 19 %( 4/21). 　CONCLUSION: This study shows that long-term treatment of RA with Lef is effec tive and safe.

Leflunomide in treating rheumatoid arthritis: a double-blind study / 中国新药与临床杂志

treating rheumatoid arthritis.　METHODS: Eighty patients with rheumatoid arthritis were randomly divided into two groups with each group having 40 patients. Group one (M 8, F 32; age 46 a± s 11 a; disease history 63 mo±48 mo) was treated with anti-inflammation sub-group No.1 and No.3. Group two (M 6, F 34; 44 a±9 a; disease history 45 mo±45 mo) was treated with sub-group No.2 and No.4. One week before the initiate of the study, the originally used non-steroid anti-inflammation drugs were stopped for all two-groups patients and each patient took 2 tablets of oxaprozin po qn. At the beginning of the study the patients received 2 tablets of anti-inflammation drugs No.1 daily and 6 tables of No.3 weekly in 1st group, and 2 tablets of anti-inflammation drugs No.2 daily and 6 tablets of No.4 weekly in 2nd group respectively.　RESULTS: In the leflunomide group, the total effect rate was 93 % and the remarkable improvement rate was 85 %. In the methotrexate group, the total effect rate was also 93 % and the remarkable effect rate was 83 %, P>0.05. Nine patients (23 %) in leflunomide group had adverse reaction as mainly skin itch, nettle-like rash, decrease of leukocytes, liver malfunction and others. Seventeen parients (43 %) in methotrexate group had adverse reaction as mainly responses of digestive tract, liver enzyme elevation, decrease of leukocytes, trichomadesis, manoxenia, and others.　CONCLUSION: Leflunomide has similar therapeutic efficacy to methotrexate. However, it has relatively less toxicity.