Takashi Shimauchi

Impact of methotrexate dose on efficacy of adalimumab in Japanese patients with rheumatoid arthritis: Results from registered data analyses

Abstract Objective: Upper limit of methotrexate (MTX) for patients with rheumatoid arthritis (RA) was recently increased from 8 to 16 mg/week in Japan. We therefore examined the effect of concomitant MTX dose on the efficacy of adalimumab (ADA) in clinical practice. Method: Sixty-one consecutive RA patients treated with ADA were followed for minimum 52 weeks and retrospectively compared by MTX dose; patients receiving concomitant MTX of 10 mg/week or more (MTX ≥10 mg group) and <10 mg/week (MTX <10 mg group). Disease activity and remission were evaluated by the disease activity score 28 (DAS28) criteria. Results: The MTX ≥10 mg group consistently showed better improvement in DAS28 and resulted in more patients (52.8%) with DAS28-remission compared with the MTX <10 mg group (26.1%). Multivariate analysis showed that MTX ≥10 mg had a significant effect on DAS28 remission with odds ratio of 5.12. ADA retention rate was 72.2% in MTX ≥10 mg group compared with 52.0% in MTX <10 mg group. Discontinuation of ADA due to adverse events were comparable in the MTX ≥10 mg and MTX <10 mg groups (11.1% vs. 12.0%). Conclusions: These findings support the critical role of concomitant MTX in the efficacy of ADA, and recommend use of MTX ≥10 mg in Japanese RA patients.

Effect of HEBP (1-hydroxyethylidene-1, 1-bisphosphonic acid) on inflammation-mediated osteopenia in the rat

Trabecular bone volume of rat leg bones decreased following the subcutaneous injection of talcum (magnesium silicate). The effect of HEBP (1-hydroxyethylidene -1, 1-bisphosphonic acid) on this osteopenia was investigated.Bone mineral content (σGs/D) of the tibia decreased at both metaphysis and diaphysis during 3 week observation period following the inflammatory stimulus, and HEBP inhibited the decrease of σGs/D at metaphysis when administrated together with talcum. Breaking stress at mid point of the femur decreased significantly and femur ash contents showed a significant percent decrease of ash weight and ash volume with talcum administration. HEBP did not improve these parameters. Talcum significantly increased serum concentration of P and alkaline phosphatase level, but HEBP had no remarkable change in these serum parameters. This type of osteopenia can serve as a working model for osteoporosis and HEBP protected the trabecular bone loss at metaphysis of this model.