ATLANTA – Methotrexate was an effective and well-tolerated treatment for juvenile localized scleroderma in a randomized, double-blind, placebo-controlled trial involving 70 patients with active disease.
Dr. Francesco Zulian
At the end of the 12-month study, 31 of 46 patients randomized to receive methotrexate had responded to treatment and were flare-free, compared with 7 of 24 patients given placebo, Dr. Francesco Zulian reported at the annual meeting of the American College of Rheumatology.
Methotrexate patients received a weekly oral dose of 15 mg/m2 (maximum, 20 mg) for 12 months or until flare of disease. Patients in the placebo group received a placebo administered in the same fashion for 12 months or to flare. Patients in both groups received prednisone at a dose of 1 mg/kg per day, with a maximum dose of 50 mg, for 3 months. They were then tapered to 0 over 1 month. During the initial 3 months of the study, treatment response was comparable for the two groups. Differences in response rates began to emerge after that point, said Dr. Zulian of the University of Padua (Italy).
Patients’ lesions were evaluated using a computerized scoring system, and changes were quantified using a skin score rate. Active lesions were monitored based on clinical examination and serial thermography. The mean skin score rates decreased significantly from 1.0 at baseline to 0.79 in the patients on methotrexate, but did not decrease in the patients given placebo. The mean target lesion temperature on thermography decreased by 44% in the methotrexate group and by 12% in the placebo group, a significant difference, he said.
Adverse events occurred in 26 of 46 patients in the methotrexate group, and in 11 of 24 in the placebo group. In the methotrexate group, adverse events included alopecia, nausea, headache, fatigue, hepatotoxicity, weight gain, and striae rubra. The only adverse events in the placebo group were weight gain and striae rubra.
Interestingly, weight gain of more than 5% of body weight occurred in 11% of the methotrexate patients and 42% of the placebo patients, Dr. Zulian said, noting that this may suggest there is some "biological or pathophysiological link" between prednisone and methotrexate that tempers this steroid-related side effect.
None of the side effects was severe enough to stop treatment, but there was a high drop-out rate – due to relapse or lack of response – in both groups; 31 of 46 patients in the methotrexate group, and 7 of 24 in the placebo group, completed the study. At the end of the 12-month study, 17 of 24 patients randomized to placebo had experienced a relapse, compared with 15 of 46 patients randomized to the methotrexate group.
Patients included in the study were aged 6-17 years with active localized scleroderma of linear, generalized, or deep subtypes with onset before age 16. The treatment and placebo groups were similar in regard to clinical and immunological features, as well as mean disease duration of about 2 years, and the absence of immunosuppressive treatment in the 6 months prior to enrollment.
Many treatments have been tried in patients with juvenile localized scleroderma, and methotrexate has emerged as one of the most frequently used drugs for this condition.
"The findings of this study show that a combination of methotrexate and prednisone is of benefit and is well tolerated as treatment for severe course juvenile localized scleroderma," Dr. Zulian said.
Prior studies have shown efficacy ranging from 74% to 93%, but the findings of those studies have been based mostly on clinical judgment, while the current study utilized more objective evaluation criteria, including thermography, and skin score rates calculated based on computerized skin scoring, he said.
"The inclusion of standardized objective parameters represents an innovative way to assess the disease and compare progression in future clinical trials," he added.
Dr. Zulian said he had no relevant financial disclosures.