| ORIGINAL ARTICLE Therapeutic effects of the combination of methotrexate and bucillamine in early rheumatoid arthritis: a multicenter, double-blind, randomized controlled study
Yoichi Ichikawa1, 16 , Terunobu Saito2, Hisashi Yamanaka2, Masashi Akizuki3, Hirobumi Kondo4, Shigeto Kobayashi5, Hisaji Oshima6, Shinichi Kawai7, Nobuaki Hama1, Hidehiro Yamada1, Tsuneyo Mimori8, Koichi Amano9, Yasushi Tanaka10, Yasuo Matsuoka11, Sumiki Yamamoto12, Tsukasa Matsubara13, Norikazu Murata14, Tomiaki Asai15, Yasuo Suzuki1 and MTX BUC Combination Study Group,, Japanese Ministry of Health, Labour and Welfare's, “Research for Establishment of Therapeutic Guidelines in, Early Rheumatoid Arthritis”1
| (1) |
Department of Rheumatic, Collagen and Allergic Diseases, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki 216-8511, Japan |
| (2) |
Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan |
| (3) |
Department of Internal Medicine, Yokohama Municipal Citizens' Hospital, Yokohama, Japan |
| (4) |
Department of Internal Medicine, Kitazato University School of Medicine, Kitazato, Japan |
| (5) |
Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, Japan |
| (6) |
Department of Internal Medicine, Fujita Health University, Nagoya, Japan |
| (7) |
Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Japan |
| (8) |
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan |
| (9) |
Second Department of Internal Medicine, Saitama Medical Center, Kawagoe, Japan |
| (10) |
Department of Internal Medicine, Konan Kakogawa Hospital, Kakogawa, Japan |
| (11) |
Department of Internal Medicine, Kawasaki Municipal Hospital, Kawasaki, Japan |
| (12) |
The Centre for Rheumatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan |
| (13) |
Department of Orthopedics, Matsubara Mayflower Hospital, Hyogo, Japan |
| (14) |
Department of Rheumatology, National Hospital Organization, Osaka Minami Medical Center, Osaka, Japan |
| (15) |
Department of Orthopedics, National Hospital Organization, Nagoya Medical Center, Nagoya, Japan |
| (16) |
Present address: St. Joseph's Hospital, 28 Midorigaoka, Yokosuka 238-8502, Japan |
Received: 26 May 2005 Accepted: 27 June 2005
Full Text
> Click Here （member's only）
Abstract Disease-modifying antirheumatic drug (DMARD) combination therapies are used widely, but there have been few reports clearly demonstrating that combination therapy is more effective than DMARD monotherapy. We conducted a multicenter, double-blind controlled trial in order to clarify that the combination of methotrexate and bucillamine is more effective than either alone. The subjects of this study were 71 patients with active rheumatoid arthritis within 2 years of onset. Dosages were 8 mg methotrexate with 5 mg folic acid per week (MTX group), 200 mg bucillamine per day (BUC group), or both MTX and BUC (combination group). Clinical effects and adverse reactions were observed for 96 weeks. The ACR 20 response rate was 79.2% in the combination group, significantly higher than the rates of 43.5% for the MTX group (P = 0.008) and 45.8% for the BUC group (P = 0.0178). The cumulative survival curve of maintaining the ACR 20 response was significantly higher in the combination group than in the MTX and BUC groups (P = 0.0123 and P = 0.0088, respectively). The mean increase in the total Sharp score over 96 weeks was 12.6 ± 9.0 in the combination group, significantly lower (P = 0.0468) than the value of 28.0 ± 28.3 for the single DMARD (combined MTX and BUC) group. The incidence of adverse reactions did not differ significantly between the three groups. It was concluded that the combination therapy with MTX and BUC showed significantly higher clinical efficacy than either of the single DMARD therapies.
Key words Bucillamine - Combination therapy - Methotrexate - Rheumatoid arthritis
|
