Subcutaneous Methotrexate Effective for Moderate to Severe Plaque Psoriasis

By Will Boggs MD

NEW YORK (Reuters Health) - An intensified dosing schedule of subcutaneous methotrexate is effective in patients with moderate to severe plaque-type psoriasis, according to results from the 52-week METOP trial.

U.S. and European guidelines recommend methotrexate as a first-line systemic drug for moderate to severe psoriasis, but the optimum dosing scheme, route of administration, and safety profile are uncertain. In recent trials of methotrexate versus biological drugs, methotrexate was started at either 5 or 15 mg/week p.o., which "might be a suboptimum route of administration in view of a trial in patients with rheumatoid arthritis that showed superiority of subcutaneous over oral methotrexate," according to the METOP researchers.

In a randomized multicenter trial, Dr. Kristian Reich from Dermatologikum Hamburg, Germany and colleagues tested an intensified subcutaneous dosing scheme of methotrexate in 120 patients with moderate to severe plaque-type psoriasis.

Patients received either methotrexate at a starting dose of 17.5 mg/week or placebo for the first 16 weeks, followed by methotrexate treatment of all patients until week 52. Patients who did not achieve at least a 50% reduction in baseline Psoriasis Area and Severity Index (PASI) score after 8 weeks of methotrexate treatment could have their doses escalated to 22.5 mg/week.

At week 16, 41% of patients in the methotrexate group and 10% of patients in the placebo group had achieved a PASI 75 response, according to the December 21st Lancet online report.

Just over a quarter of methotrexate patients (27%) were rated as clear or almost clear at 16 weeks, compared with only 7% of placebo patients.

By week 52, 73% of patients had achieved PASI 75, 45% had achieved PASI 90, and 18% had achieved PASI 100, with 64% rated by physicians as clear or almost clear.

Improvements in psoriasis were paralleled by improvements in the health-related quality of life.

Adverse events were as expected with methotrexate treatment, according to the authors. Gastrointestinal disorders and increases in hepatic enzymes were more common with methotrexate than with placebo. There were no deaths, malignancies, or major adverse cardiovascular events, and no serious adverse events were attributed to methotrexate.

"Our findings encourage the use of subcutaneous methotrexate for treatment of psoriasis, and suggest long-term clinical outcomes better than previously reported for oral administration, although final confirmation will be needed in a direct head-to-head trial of subcutaneous versus oral dosing," the researchers conclude. "Our findings might also help to guide future recommendations for the optimum dosing of methotrexate."

Dr. Dafna D. Gladman from Toronto Western Hospital, Toronto, Ontario, Canada, whose editorial questioned whether methotrexate should remain the first-line drug for psoriasis, told Reuters Health by email, "While methotrexate has a certain efficacy in psoriasis, it is not as good as the efficacy now obtained with the new biologic agents."

"Patients with moderate to severe psoriasis who do not respond to topical medications and/or light therapy should probably be offered methotrexate," she said. "It may be that methotrexate should be offered earlier to patients who have severe psoriasis."

"I think the message from the paper is that subcutaneous methotrexate is the best mode of administration of the drug if one wants to get the best results," Dr. Gladman added.

Medac funded the trial and had various relationships with five of the 10 authors.

Dr. Reich did not respond to our request for comments.

SOURCE: https://bit.ly/2iOkFsU and https://bit.ly/2iywUGu

Lancet 2016.

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