title: Effect of Methotrexate Plus Adalimumab on the Achievement of Rheumatoid Arthritis Therapeutic Goals: Post Hoc Analysis of Japanese Patients (MELODY Study).
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier, NCT01076959.
  
  
  BACKGROUND
  AbbVie and Eisai Co., Ltd.
authors.affiliation: NTT Sapporo Medical Center, Sapporo, Japan. tkoike@med.hokudai.ac.jp.
authors.forename: Takao
authors.initials: T
authors.lastname: Koike
authors.affiliation: Department of Epidemiology and Pharmacoepidemiology of Rheumatic Diseases, Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Harigai
authors.affiliation: Department of Orthopedic Surgery, Nagoya University School of Medicine, Nagoya, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Ishiguro
authors.affiliation: Department of Allergy and Rheumatic Diseases, Japanese Red Cross Medical Center, Tokyo, Japan.
authors.forename: Shigeko
authors.initials: S
authors.lastname: Inokuma
authors.affiliation: Department of Maternal and Child Health Nursing, School of Health Science, Faculty of Medicine, Kagoshima University, Kagoshima, Japan.
authors.forename: Syuji
authors.initials: S
authors.lastname: Takei
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takeuchi
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamanaka
authors.affiliation: Department of Internal Medicine and Rheumatology, Faculty of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Takasaki
authors.affiliation: Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Tsuneyo
authors.initials: T
authors.lastname: Mimori
authors.affiliation: AbbVie GK, Tokyo, Japan.
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Hiramatsu
authors.affiliation: AbbVie GK, Tokyo, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Komatsu
authors.affiliation: Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Tanaka
keywords: Adalimumab; Doses; Effectiveness; Methotrexate; Rheumatoid arthritis; Safety