In a study of patients with difficult-to-treat chronic spontaneous urticaria, methotrexate was not superior to placebo for improving complete remission rates when combined with H1 antihistamines. Findings from this study were published in the Journal of the American Academy of Dermatology.

Adult patients with chronic spontaneous urticaria resistant to H1 antihistamines were enrolled in the study if they had received ≥3 different molecules of H1 antihistamines or H1 antihistamines with a double or higher dose between 2011 and 2016. The investigators randomly assigned patients to either an 18-week course of oral methotrexate .2 mg/kg/wk plus H1 antihistamines (n=39) or placebo .2 mg/kg/wk plus H1 antihistamines (n=36). Dosages of both methotrexate and placebo were increased to .25 mg/kg/wk at 4 weeks if lack of efficacy was noted.

The primary outcome of the double-blind, placebo-controlled trial was complete urticaria remission at 18 weeks. Additional outcomes were pruritus, number of outbreaks per week, lesion duration, quality of sleep, quality of life, safety, and the number of lesions on the face and/or neck.

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At 18 weeks, 3 patients who received methotrexate (7.9%) and 0 patients who received placebo (0%) had complete remission (difference, 7.9 percentage points; 95% CI, -4.0 to 20.8; P =.24). In the complete case analysis, there was also no significant difference between the methotrexate and placebo groups with regard to complete remission at 18 weeks (8.6% vs 0%, respectively; difference, 8.6; 95% CI, -3.8 to 22.4; P =.24). No difference was found between the groups in the change of quality of life scores over time and there was no difference in the proportion of adverse events throughout the study.

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A limitation of the study was the small sample size, which the researchers explained may have led to an underpowered analysis for detecting the primary outcome.

The researchers added that “Methotrexate has immunomodulatory and anti-inflammatory effects and probably leads to reduced level of functional autoantibodies.”

Disclosure: Several of the study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

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Leducq S, Samimi M, Bernier C, et al. Efficacy and safety of methotrexate add-on therapy versus placebo for patients with chronic spontaneous urticaria resistant to H1-antihistamines: a randomized, controlled trial [published online August 5, 2019]. J Am Acad Dermatol. doi:10.1016/j.jaad.2019.07.097.