December 2, 2022

Add-On Methotrexate Plus Non-superior antihistamine to placebo in difficult-to-treat chronic spontaneous urticaria


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

Adult patients with spontaneous chronic urticaria resistant to H1 antihistamines were included 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. cure one week of oral methotrexate 0.2 mg / kg / week plus H1 antihistamines (n = 39) or placebo 0.2 mg / kg / week plus H1 antihistamines (n = 36). Doses of methotrexate and placebo were increased to 0.25 mg / kg / week at 4 weeks if lack of efficacy was noted.

The primary endpoint of the double-blind, placebo-controlled trial was complete remission of urticaria at 18 weeks. Additional outcomes were pruritus, number of outbreaks per week, duration of lesions, quality of sleep, quality of life, safety, and 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 full case analysis, there was also no significant difference between the methotrexate and placebo groups for 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 groups in the change in quality of life scores over time and there was no difference in the proportion of adverse events throughout the study.

One limitation of the study was the small sample size, which the researchers said may have led to an undernourished analysis to detect the primary outcome.

The researchers added that “methotrexate has immunomodulatory and anti-inflammatory effects and probably leads to a reduction in the level of functional autoantibodies.”

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

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Leducq S, Samimi M, Bernier C, et al. Efficacy and safety of add-on treatment to methotrexate versus placebo in 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.