ABANO TERME, ITALY — Intravenous methotrexate proved to be an effective steroid-sparing treatment for recalcitrant cutaneous lupus, Dr. Joerg Wenzel reported at a congress on skin, rheumatism, and autoimmunity.
Dr. Wenzel and his associates in the department of dermatology at the University of Bonn (Germany) retrospectively analyzed patients who underwent treatment with methotrexate and whose skin lesions had not responded to antimalarials, azathioprine, mycophenolate mofetil, or dapsone.
Initially, the drug was given intravenously to 43 patients in doses of 15–25 mg/week. The dose was titrated down to a final range of 7.5–15 mg/week in eight patients. The oral route in doses of 10–20 mg/week was substituted in seven patients because of lack of compliance.
Disease activity was rated using a cutaneous lupus activation index (CLAI) that provided a single score reflecting the degree of skin involvement, grade of inflammation, and clinical course. At baseline, the mean CLAI was 5.13; this decreased to 1.73, with clinical response being observed after 2–8 weeks, Dr. Wenzel said. This was a “highly significant” decline in disease activity, and all but one patient experienced improvement, he said.
The greatest improvement was seen among 16 patients with the subacute cutaneous subtype of lupus erythematosus. Among these patients, the mean CLAI fell from 5.5 to 1.2, he said. Seven patients (16%) discontinued treatment because of significant side effects, including elevations of liver enzymes and pancytopenia. These quickly resolved when treatment was discontinued.
In 15 patients, administration was switched to the subcutaneous route, using a methotrexate formulation. Efficacy was equivalent to that seen with intravenous administration, and side effects were similar. There were significant differences in adverse effects, however, with parenteral administration, compared with oral delivery, probably because of individual differences in gastrointestinal resorption.
“My personal view is that the subcutaneous route opens the door to patient self-administration,” Dr. Wenzel said.
One curious finding in the study was that patients who had extensive lymphocytopenia before treatment experienced a significant increase in lymphocyte counts. This finding following methotrexate administration was strange, he said, as methotrexate itself is an immunosuppressive drug that can cause pancytopenia.
“I believe methotrexate blocks the recruitment of circulating autoreactive, cytotoxic lymphocytes from the blood into the skin,” he said. This hypothesis is supported by recent findings in psoriasis, where methotrexate reduced the expression of the skin-homing molecule cutaneous lymphocyte-associated antigen (Exp. Dermatol. 2004;13:426–34).