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Is parenteral methotrexate worth trying?
  1. A OSMAN,
  1. Department of Rheumatology
  2. Cannock Chase Hospital
  3. Cannock WS11 2XY, UK
  1. Dr Mulherin

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Methotrexate is widely accepted as a useful disease modifying drug for the management of rheumatic diseases, against which new treatments are often compared.1-3 However, apart from those who are intolerant of oral methotrexate despite folate supplementation, some patients simply do not respond. This may relate to compliance, but may also reflect pharmacokinetic variables, which influence the absorption of oral methotrexate.4 ,5 To overcome compliance and pharmacokinetic problems, some units have begun using parenteral methotrexate, either intramuscular or subcutaneous, the latter providing the potential for self treatment.6However, although some authors have shown that parenteral methotrexate works,7 and many have examined the theoretical aspects of such treatment,4 ,5 hardly any have examined the clinical utility of switching patients from oral to parenteral methotrexate.

In this small cross sectional study we examined the case notes of all 24 patients (17 female) who had started treatment with intramuscular methotrexate at this rheumatology department. The indication for methotrexate treatment was mostly rheumatoid arthritis (RA), except for one patient with polymyositis and one with juvenile arthritis. Mean (range) age was 56 (9–70) years. Median (range) dose of oral methotrexate was 17.5 (5–25) mg a week before the initiation of intramuscular methotrexate. At the time that the case notes were reviewed, 20 patients had improved, one patient was worse, and three were unchanged—an assessment reached by reviewing their clinicians' most recently recorded observations. Median (range) duration of parenteral treatment was 5 (1–55) months and dose of parenteral methotrexate at the time of this review was 15 (7.5–25) mg a week. Mean (range) C reactive protein fell from 53 (5–122) measured at the time parenteral methotrexate was started to 34 (7–111) mg/l when the case notes were reviewed.

It seems inevitable that the role of parenteral methotrexate will expand as institutions resolve the issues related to delivery of treatment and disposal of the cytotoxic waste it engenders. It also seems highly unlikely that a substantial clinical trial comparing continued oral treatment with initiation of parenteral methotrexate in patients unresponsive to oral methotrexate will ever be performed. At least this small study suggests that not only is it a development that ought to work but also it actually seems to improve disease control for these patients.


We thank Doctor Tom Price and Doctor Thomas Sheeran for allowing us to include their patients in this study. We thank our First Community Trust nursing colleagues for identifying the patients.