VALENCIA, Spain - Children with localized scleroderma responded better to methotrexate than to prednisone in a small, placebo-controlled trial.
“Although localized scleroderma is rather rare, it can be very aggressive and lead to complications in some patients,” Dr. Francesco Zulian said at the 17th Pediatric Rheumatology European Society Congress. “Some patients can have psychological sequelae as well, if the lesions occur on the face.”
Dr. Zulian described his 12-month study, dubbed the INSIEME Project. An Italian study, the double-blind placebo-controlled trial compared two therapeutic strategies - prednisone alone and prednisone plus methotrexate – for the treatment of juvenile localized scleroderma (JLS). This project involved 21 Italian pediatric rheumatology and dermatology centers.
The study evaluated 70 patients (mean age, 10 years) who had a mean disease duration of 2 years and a mean disease onset of 7 years. All had active disease for at least 6 months, and none had been exposed to immunosuppressant therapy for 6 months before enrollment.
Of these, 46 were randomized to receive methotrexate (15 mg/m2; maximum dose, 20 mg) once a week plus daily oral prednisone (1 mg/kg per day; maximum, 50 mg). The control group took a weekly placebo plus the daily prednisone. In both groups, the prednisone was tapered after 3 months, with a complete cessation by month 4. Treatment with methotrexate or placebo was continued for 12 months or to the time of a flare.
The investigators measured the size of existing lesions, noted any new lesions, and measured skin temperature to evaluate response. “Skin lesions were evaluated by a computerized scoring system; changes were quantified by the skin score rate [SSR]. Clinical examinations and series thermography monitored the changes in active lesions,” said Dr. Zulian of the University of Padua (Italy).
Treatment response was the primary end point. Responders were defined as those who achieved an SSR of less than 1, a decrease in lesion temperature of at least 10% compared with baseline, and no new lesions during treatment.
Relapse was defined as an SSR of more than 1, unchanged or increased lesion temperature, or the appearance of new lesions.
In phase 1 (0-3 months), all of the patients were taking prednisone, plus either methotrexate or placebo. “During this time, the skin score rate indicated a similar, good response in both groups,” Dr. Zulian said. But from 6 to 9 months, after the prednisone taper was complete, significantly more flares began to appear in the control group (71% vs. 33%). This led to a large dropout rate in the placebo group, with only 7 of the original 24 completing the trial. However, “there was a consistent response in the methotrexate groups,” Dr. Zulian noted.
The mean skin score rate decreased from 1 to 0.79 in the methotrexate group, but did not change in the placebo group. The mean temperature of the target lesion decreased by 44% in the methotrexate group and 12% in the placebo group - a significant difference. New lesions appeared in 6.5% of the patients taking methotrexate and 17% of those taking placebo, also significantly different.
After 12 months, there were significantly more responders in the methotrexate than the placebo groups (67% vs. 29%).
Mild side effects occurred in 56% of the methotrexate group and 46% of the placebo group, but none were serious enough to stop treatment, Dr. Zulian added. “The methotrexate was well tolerated and effective.”