Subcutaneous injection of methotrexate: advantages in the treatment of rheumatoid arthritis


 Methotrexate is a conventional synthetic disease-modifying anti-rheumatic drug, that is used in the treatment of rheumatoid arthritis. However, insufficient responses to oral methotrexate at lower doses as well as increased variation of drug bioavailability and a deteriorated safety profile during dose escalation are regularly observed in patients. Some of its main side effects may be overcome by temporary drug hiatus, dose reduction or can be counterbalanced with folic acid.
 Especially gastrointestinal side effects are a major reason for permanent treatment discontinuation. Recent data suggest that methotrexate in a subcutaneous injection formulation can reduce gastrointestinal effects and thus, may allow to overcome oral intolerance and improve drug survival.
 Here, we review the currently available literature on efficacy and safety of subcutaneous methotrexate in comparison to oral methotrexate in treatment of patients with rheumatoid arthritis. Despite of some inconsistency between data, an improvement in the efficacy and/or safety profile of subcutaneous methotrexate has been demonstrated.
 In the USA, subcutaneous methotrexate is an established second-line treatment already, while in European countries this formulation is even recommended as a first-line treatment. With the recent approval of subcutaneous methotrexate in Japan another beneficial treatment option is now available for Japanese patients with rheumatoid arthritis.