Children taking injectable methotrexate had more severe disease activity when they entered the study than those in the oral group. Despite this difference, patients in both groups got a similar dose of methotrexate, about 0.4 mg/kg.

Both oral and injections of methotrexate were similarly effective, with 73 percent of the oral group and 72 percent of the injectable group achieving at least a 30 percent improvement in signs and symptoms of JIA after 6 months of treatment. A similar percentage of patients in both groups achieved a 50 percent and a 70 percent improvement in signs and symptoms of disease at 6 months.

Safety data showed that 22 percent of the oral group and 27 percent of subcutaneous group experienced at least one documented side effect (including gastrointestinal symptoms, infectious events, fatigue, blood abnormalities, uveitis). But significantly more injection patients (11 percent) discontinued methotrexate due to side effects than patients taking oral methotrexate (5 percent).

Folic acid supplementation, which is used to prevent side effects of methotrexate – such as gastrointestinal distress and elevation of liver enzymes – was given to 46 percent of the oral group and only to 32 percent of the injectable group. (Dr. Wallace notes that in the US, folic acid is typically given to all patients on methotrexate.) But there were no difference in the frequency of discontinuation in those patients who did and did not receive folic acid.

Dr. Wallace calls this study provocative and interesting – but interprets the results of this report cautiously. “Registry studies may have missing data that can be a potential problem,” she says, pointing out that the study’s safety data are difficult to interpret, details on corticosteroid use (oral and injected) was not provided, and whether patients were on nonsteroidal anti-inflammatory drugs, or NSAIDs, when they experienced an adverse event was not reported. Many of the side effects attributed to methotrexate may also occur with NSAIDs, she says.

She, like the study authors, says that a clinical trial comparing the two different routes of methotrexate administration in JIA patients would be “incredibly helpful.”

And Dr. Wallace – whose research has focused on early and aggressive treatment for JIA, including the use of a biologic in addition to methotrexate – says she would be interested in a follow up of this group of patients. “Treatment of JIA is an evolving area. It would be interesting to know how many patients from this 2005 to 2009 cohort continued on methotrexate alone after six months with achieving inactive disease,” she says. “Currently, most patients would be started on methotrexate earlier in [the course of the] disease than the average disease duration of 1 year in this report. Earlier treatment may provide different efficacy between the routes of treatment.”