COEUR D’ALENE, IDAHO – Long-term use of methotrexate has a lot going for it as first-line therapy for active juvenile localized scleroderma, according to Dr. Francesco Zulian, chief of pediatric rheumatology at the University of Padua (Italy).
"It’s a drug that’s very old, it’s not expensive, it’s used in many dermatologic and rheumatologic conditions – and it is very useful in patients with scleroderma," he observed in his Sidney Hurwitz Memorial Lecture at the annual meeting of the Society for Pediatric Dermatology.
Dr. Francesco Zulian
The initial studies of methotrexate in scleroderma were conducted in adults. Dr. Zulian and colleagues are credited with performing the first randomized, double-blind, prospective clinical trial in pediatric patients, building upon other investigators’ favorable earlier nonrandomized results.
Based upon the randomized trial findings and the subsequent long-term follow-up study, his recommendation for patients with active juvenile localized scleroderma – whether of the linear, pansclerotic, or generalized morphea subtype – is 3 months of initial bridging therapy with a combination of methotrexate plus systemic corticosteroids, followed by at least 24 months of methotrexate without systemic steroids.
In the long-term follow-up study involving 65 patients, treatment was associated with a 74% clinical remission rate. This broke down as approximately a 54% complete remission rate maintained for at least 6 months without treatment, and a 20% clinical remission rate on treatment. Treatment for less than 24 months yielded lesser long-term benefit. Adverse effects were seen in nearly half of patients; however, they were typically mild, and no patients discontinued treatment as a result (J. Am. Acad. Dermatol. 2012;67:1151-6).
"This study shows there is a large group of patients who get better with a relatively mild treatment," Dr. Zulian noted.
The bridging therapy regimen employed in the landmark double-blind, placebo-controlled trial involved oral methotrexate at 15 mg/m2 or a maximum of 20 mg per week, along with prednisone at 1 mg/kg/day or a maximum of 50 mg daily for 3 months (Arthritis Rheum. 2011;63:1998-2006).
In his own clinical practice, Dr. Zulian said, he turns to mycophenolate mofetil (CellCept) in the minority of cases in which bridging therapy with methotrexate and prednisone proves inadequate.
In patients with circumscribed morphea as defined in the international Padua consensus conference guidelines, subsequently formalized by the American College of Rheumatology, the European League Against Rheumatism, and the Pediatric Rheumatism European Society (Arthritis Rheum. 2007;203-12), his recommended treatment is topical corticosteroids, calcipotriol, or phototherapy.
While scleroderma is a rare condition in children, it is nonetheless the third most frequent condition within pediatric rheumatology. For physicians with affected patients who are interested in collaborative research to advance the treatment and understanding of this disease, Dr. Zulian recommended contacting the Juvenile Scleroderma International Network (www.jusinet.org).
Dr. Zulian reported having no financial conflicts with regard to his presentation.