RA Patient Not Responding to MTX? Try SubQ Next

May 09, 2014

A small crossover study shows that methotrexate delivered subcutaneously provides greater exposure to the drug, and may help rheumatoid arthritis patients not reaching remission with the oral form.

Schiff MH,  Jaffe JS, Freundlich B. Head-to-head, randomised, crossover study of oral versus subcutaneous methotrexate in patients with rheumatoid arthritis: drug-exposure limitations of oral methotrexate at doses ≥15 mg may be overcome with subcutaneous administration.Ann Rheum Dis. (2014) doi:10.1136/annrheumdis-2014-205228 [Online first  April 12-2014]

Rheumatoid arthritis (RA) patients with an unsatisfactory response to oral methotrexate (MTX) may benefit from switching to subcutaneous MTX, which allows higher drug dosing.

This multicenter, open-label, three-way crossover study, led by researchers from the University of Colorado, assigned patients
in groups of 12 to receive MTX at weekly doses of 10mg, 15mg, 20mg, or 25 mg, administered in a random sequence of three treatments -- oral MTX or subQ MTX injected into the abdomen or the thigh, using an auto-injector device.  

The authors note that oral MTX doses above 15 mg are used routinely to control disease activity in RA, but some patients tolerate them poorly and others don't find adequate benefit from the drug. Previous studies have suggested that the limited systemic exposure of oral formulations may reduce its efficacy.

Among the 47 patients who completed the study (most of them white women in their 60’s who had been taking MTX for at least three months), subQ MTX produced a greater increase in systemic exposure at each dose, while MTX exposure plateaued with oral doses at or above 15 mg/week.

Both formulations were generally safe and well-tolerated with no unexpected adverse events.

Small numbers and the random-sequence crossover design are limitations to this study, but the researchers conclude that it shows subQ MTX may help to achieve optimal results in some cases.