The Pharmaceutical Journal
Vol 273 No 7319 p456
2 October 2004

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Consider intramuscular methotrexate when oral route fails in rheumatoid arthritis

Switching high dose oral methotrexate to the intramuscular route may improve efficacy in rheumatoid arthritis (RA).
So suggests French research published recently, although British rheumatologists proposed this approach last year.

The researchers switched 143 patients with RA from IM to oral methotrexate because of a shortage of the injectable formulation. Of these, 47 were switched back to the IM form. A questionnaire was then sent to patients to evaluate efficacy and tolerance of the different routes.

When patients were switched to the oral form, disease activity and symptoms increased. There was also a greater frequency of gastrointestinal symptoms though no increase in liver abnormalities. In patients switched back to the injectable drug, disease manifestations improved and side effects reduced. The authors urge clinicians to consider IM methotrexate when RA remains active in spite of high doses of the oral agent.

Christopher Green, assistant director of pharmacy, Royal Liverpool and Broadgreen University Hospital, told The Journal that many patients experienced adverse GI effects with oral methotrexate, particularly at the time of dosing.

“To stop what is the gold standard treatment for RA for this reason is somewhat frustrating for all concerned, particularly if it is otherwise working well for the patient,” he commented. He added that poor response to the oral agent could also be due to impaired absorption.

Dr Green said that injectable methotrexate is used in the UK to varying extents. Such use could alleviate GI side effects and also circumvent problems associated with poor absorption from the gut. However, parenteral methotrexate is currently unlicensed in RA. Shared care between primary and secondary care is further complicated by the fact it is a cytotoxic agent.

Workers at Leeds General Infirmary last year advocated trying parenteral methotrexate before switching patients to tumour necrosis factor blockade (Rheumatology 2003;42:1009).