Added Leukotriene Receptor Antagonists Show Benefits in Chronic Urticaria

Derick Alison
Derick Alison
5 Min Read

ANAHEIM, Calif. — Adding leukotriene receptor antagonists (LTRAs) to antihistamines appears to reduce the severity of chronic urticaria, according to a systematic review and meta-analysis of randomized trials.

Among 33 unique randomized trials including over 3,100 patients, high-certainty evidence suggested a mean difference in weekly Urticaria Activity Score (UAS7) of -5.17 (95% CI -6.53 to -3.80) with added LTRAs compared with antihistamines alone, reported Daniel Rayner, BHSc, of McMaster University in Hamilton, Ontario, during the American College of Allergy, Asthma & Immunology (ACAAI) annual meeting.

High-certainty evidence also suggested that itch and wheal count were improved, with mean differences in the numerical rating scale of -0.25 (95% CI -0.39 to -0.10) and -0.25 (95% CI -0.41 to -0.08), respectively.

In addition, the mean difference in the Dermatology Life Quality Index (DLQI), measuring quality of life, was -4.40 (95% CI -8.15 to -0.65), though the certainty of evidence was considered to be low.

LTRAs are commonly used for a wide array of inflammatory conditions, but concerns about potential associations between LTRAs and increased risks of adverse neuropsychiatric events remain. These concerns stem from post-marketing data, as well as data from the FDA’s Adverse Event Reporting System (FAERS).

In 2020, the FDA required a boxed warning for montelukast (Singulair), a commonly used LTRA, due to the possibility of “serious mental health side effects,” and encouraged risk-benefit discussions between patients and providers. Despite this, Rayner pointed out, there have been no reviews analyzing the evidence for LTRAs — currently recommended as a third-line treatment — in chronic urticaria.

“In practice, leukotriene receptor antagonists are frequently considered to be used off-label when chronic urticaria is refractory to standard treatment with H1-antihistamines,” Rayner said. “Yet the guidance, or current guideline recommendations, are inconsistent with this notion. Current guidelines demonstrate or indicate that there’s low-quality or low-certainty evidence regarding the use of these leukotriene receptor antagonists for urticaria, and that no recommendations, unfortunately, can be made.”

According to moderate-certainty evidence, LTRAs were similar to other treatments in terms of adverse events (risk ratio 0.80, 95% CI 0.56-1.15). However, none of the randomized trials examined associations between LTRAs and neuropsychiatric adverse events.

Compared with antihistamines alone, those who received added LTRAs had 13 fewer adverse events per 1,000 patients (67 vs 54 per 1,000 patients).

For this systematic review and meta-analysis, Rayner and colleagues searched databases and pharmaceutical registries from inception to March 2023; 33 randomized trials were ultimately included. Of these trials, 20 only included adults, while 12 included children. Only one trial examined zafirlukast (Accolate), while the remaining 32 investigated montelukast.

Of the 3,168 patients included in the trials, median age was 36 and 53% were women. They had been experiencing symptoms for a median of 4 weeks, and had median UAS7 scores of 31 out of 42.

Rayner told MedPage Today that angioedema was also a factor frequently left out of the studies.

“The one thing that really surprised us was that these [LTRAs] — the notion was really that they primarily would benefit patients with angioedema,” he said. “The thing is, amongst all the randomized trials we identified, we only found one study that actually evaluated angioedema activity. So, there’s very much this inconsistency between what the notion was for practice, and what actual evidence was out there.”

Findings from this meta-analysis will inform the ACAAI’s future practice parameters for urticaria.

  • author['full_name']

    Elizabeth Short is a staff writer for MedPage Today. She often covers pulmonology and allergy & immunology. Follow

Disclosures

Rayner reported no disclosures. Co-authors reported various relationships with industry and EB Medicine, publisher of Emergency Medicine Practice and Pediatric Emergency Medicine Practice.

Primary Source

American College of Allergy, Asthma & Immunology

Source Reference: Rayner D, et al “Leukotriene receptor antagonists with antihistamines versus antihistamines alone for chronic urticaria: systematic review and meta-analysis” ACAAI 2023; Abstract LB002.

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