Takao Koike1, Masayoshi Harigai2, Naoki Ishiguro3, Shigeko Inokuma4, Syuji Takei5, Tsutomu Takeuchi6, Hisashi Yamanaka7, Yoshinari Takasaki8, Tsuneyo Mimori9, Katsutoshi Hiramatsu10, Shuichi Komatsu10, Yoshiya Tanaka11. 1. NTT Sapporo Medical Center, Sapporo, Japan. tkoike@med.hokudai.ac.jp. 2. Department of Epidemiology and Pharmacoepidemiology of Rheumatic Diseases, Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan. 3. Department of Orthopedic Surgery, Nagoya University School of Medicine, Nagoya, Japan. 4. Department of Allergy and Rheumatic Diseases, Japanese Red Cross Medical Center, Tokyo, Japan. 5. Department of Maternal and Child Health Nursing, School of Health Science, Faculty of Medicine, Kagoshima University, Kagoshima, Japan. 6. Department of Internal Medicine, Division of Rheumatology, School of Medicine, Keio University, Tokyo, Japan. 7. Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan. 8. Department of Internal Medicine and Rheumatology, Faculty of Medicine, Juntendo University, Tokyo, Japan. 9. Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. 10. AbbVie GK, Tokyo, Japan. 11. Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Abstract
INTRODUCTION: There is insufficient evidence regarding the appropriate dose of methotrexate (MTX) required to achieve specific treatment goals in patients with rheumatoid arthritis (RA) receiving biologic drugs in Japan. The present study aimed to assess the dose-response effect of MTX in combination with adalimumab (ADA) to achieve low disease activity (LDA) and/or remission at 24 weeks in RA patients. METHODS: This analysis used data of the ADA all-case survey in Japan (n = 7740), and 5494 patients who received ADA and MTX were classified into five groups by weighted average MTX dose (>0-<4, 4-<6, 6-<8, 8-< 10, and ≥10 mg/week). Of the 5494 patients, 3097 with baseline 28-joint disease activity score based on erythrocyte sedimentation rate >3.2 were analyzed for effectiveness by MTX dose. RESULTS: In biologic-naïve patients (n = 1996/3097), LDA/remission rates increased with MTX up to 6-<8 mg/week and then plateaued at higher doses (LDA, p = 0.0440; remission, p = 0.0422). In biologic-exposed patients (n = 1101/3097), LDA/remission rates increased with MTX dose (LDA, p = 0.0009; remission p = 0.0143). The incidences of serious adverse drug reactions (ADRs) and serious infections did not differ by MTX dose, but total ADRs and infections were significantly higher (p < 0.05) with increased MTX doses. CONCLUSION: The appropriate MTX doses in combination with ADA to achieve LDA and/or remission at week 24 were different between biologic-naïve and biologic-exposed patients with RA, suggesting that 8 mg/week of MTX would be enough for biologic-naïve patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01076959. FUNDING: AbbVie and Eisai Co., Ltd.
INTRODUCTION: There is insufficient evidence regarding the appropriate dose of methotrexate (MTX) required to achieve specific treatment goals in patients with rheumatoid arthritis (RA) receiving biologic drugs in Japan. The present study aimed to assess the dose-response effect of MTX in combination with adalimumab (ADA) to achieve low disease activity (LDA) and/or remission at 24 weeks in RApatients. METHODS: This analysis used data of the ADA all-case survey in Japan (n = 7740), and 5494 patients who received ADA and MTX were classified into five groups by weighted average MTX dose (>0-<4, 4-<6, 6-<8, 8-< 10, and ≥10 mg/week). Of the 5494 patients, 3097 with baseline 28-joint disease activity score based on erythrocyte sedimentation rate >3.2 were analyzed for effectiveness by MTX dose. RESULTS: In biologic-naïve patients (n = 1996/3097), LDA/remission rates increased with MTX up to 6-<8 mg/week and then plateaued at higher doses (LDA, p = 0.0440; remission, p = 0.0422). In biologic-exposed patients (n = 1101/3097), LDA/remission rates increased with MTX dose (LDA, p = 0.0009; remission p = 0.0143). The incidences of serious adverse drug reactions (ADRs) and serious infections did not differ by MTX dose, but total ADRs and infections were significantly higher (p < 0.05) with increased MTX doses. CONCLUSION: The appropriate MTX doses in combination with ADA to achieve LDA and/or remission at week 24 were different between biologic-naïve and biologic-exposed patients with RA, suggesting that 8 mg/week of MTX would be enough for biologic-naïve patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01076959. FUNDING: AbbVie and Eisai Co., Ltd.
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