Scleroderma

Methotrexate is effective in juvenile localized scleroderma when given with a short course of steroids, an Italian randomized study confirmed.

Among children ages 6 to 17 receiving methotrexate, 67.4% completed the yearlong trial without flaring, compared with 29.2% of those given placebo (P<0.005), according to Francesco Zulian, MD, of the University of Padua, and colleagues. The likelihood of patients' flaring while on methotrexate was about one-third of that for placebo (HR 2.82, 95% CI 1.40 to 5.66), the researchers reported in the July Arthritis & Rheumatism.

Children with localized scleroderma can have considerable and disfiguring tissue involvement, from the skin down to the bone, while one in five also develops involvement of other organs.

Numerous topical and systemic treatments have been tried, such as corticosteroids, calcipotriol, tacrolimus, and methotrexate, but there have been no randomized trials and no treatment has been widely accepted.

Because methotrexate seemed plausible as a potential therapy, with effects on cytokines such as interleukin-6 that have been implicated in systemic sclerosis, Zulian and colleagues conducted a blinded study that included 70 patients with linear scleroderma, generalized morphea, or mixed subtype scleroderma.

Patients ranged in age from 6 to 17 years, and 50 were girls. Most had linear scleroderma, and mean disease duration was 2.3 years.

They were randomized to receive oral methotrexate, 15 mg/m2, or placebo once weekly for 12 months or until disease flared. In addition, all patients received oral prednisone in doses of 1 mg/kg per day for three months. The steroid then was gradually tapered.

Measures used to assess disease activity included a skin score rate, which represented change in lesion size independent of the increase in the child's body surface area, and inflammation measured with infrared thermography and calculated as percentage thermal change from baseline. Response to treatment was defined as a skin score rate of 1 or less, a decreased percentage thermal change of 10% or more from baseline, and no new lesions.

All patients initially responded while receiving prednisone, but after the steroid was withdrawn 70.8% of those on placebo flared, as did 32.6% of those receiving methotrexate (P<0.005). Mean percentage thermal change from baseline was −49% at three months in the methotrexate group and −50% in the placebo group. At 12 months, the change was −44% in the active treatment group but only −12% in the placebo group.

The skin score rate at three months was 0.80 in the methotrexate group and 0.81 in the placebo group. At the end of a year, however, the scores were 0.79 and 1.10, respectively (P=0.011). New skin lesions appeared in 6.5% of children on methotrexate, and in 16.7% of those on placebo.

No serious adverse events occurred, and no patients withdrew because of adverse events.

Nausea and headache were reported by 17.4% and 10.9% of the methotrexate group and by none of the placebo patients, while 41.7% of the placebo patients experienced weight gain compared with 10.9% of the methotrexate patients. The investigators noted that their study differed from previous small, unrandomized studies in the co-administration of full-dose prednisone for three months.

All patients responded to this, including the placebo patients, and almost one-third of patients receiving placebo had a sustained response after the steroid was withdrawn.

The researchers said their finding of sustained improvement for three months in patients on steroid monotherapy "supports the notion that corticosteroids are effective in rapidly inducing reduction of early inflammation in juvenile localized scleroderma and indicates that spontaneous remission may occur in a small group of patients," wrote Zulian and colleagues.

A strength of the study was the use of objective measures such as infrared thermography to evaluate disease activity. A limitation was the lack of biologic markers and the unavailability of recently proposed measurement techniques such as laser Doppler flowmetry.

Source: Walsh, N. (2011), "Methotrexate Cuts Scleroderma Flares in Kids", MedPageToday; original article can be viewed here.