Leukotriene receptor antagonists add to efficacy of antihistamines for chronic urticaria

Key takeaways:

• The addition of leukotriene receptor antagonists to antihistamines improved urticaria symptoms.
• The combination did not increase overall adverse events, but impact on neuropsychiatric events remains unclear.

ANAHEIM, Calif. — The addition of leukotriene receptor antagonists to antihistamines improved urticaria severity with little to no impact on adverse events, according to a systematic review and meta-analysis.

The study was presented as a late-breaking abstract at the American College of Allergy, Asthma & Immunology Annual Scientific Meeting.

Leukotriene receptor antagonists (LTRAs) frequently are used off-label when chronic urticaria is refractory to standard treatment with H1 antihistamines, Daniel Rayner, BHSc, of the department of health research methods, evidence and impact at McMaster University, said during his presentation.

“Yet the current guideline recommendations are inconsistent with this notion,” he said, adding that most guidelines indicate that there is low-quality evidence regarding the use of LTRAs.

“On top of this, there’s a lot of uncertainty regarding the potential harm of leukotriene receptor antagonists,” he added. “In 2020 the FDA put out a black box warning for one LTRA [montelukast], specifically in relation to serious neuropsychiatric adverse events that were observed in observational studies of patients with asthma and allergic rhinitis and, to date, there’s still a lot of uncertainty regarding the impact of LTRAs on the serious neuropsychiatric adverse events in the chronic urticaria population.”

Thus, the American Academy of Allergy, Asthma & Immunology/ACAAI Joint Task Force on Practice Parameters Chronic Urticaria Guideline Development Group commissioned Rayner and colleagues to evaluate the safety and efficacy of LTRAs in patients with chronic urticaria.

The researchers searched 13 databases to identify 33 randomized controlled trials — 32 of which evaluated montelukast and one zafirlukast — that included 3,168 patients (median age, 36 years; 53% women) with chronic urticaria and a Weekly Urticaria Activity Score (UAS7) of 31 out of a scale from 0 to 42.

Based on a high certainty of evidence — which researchers assessed using GRADE guidance —researchers found the addition of LTRAs to antihistamines improved urticaria severity by a mean difference of –5.17 (95% CI, –6.53 to –3.8) on the UAS7 scale.

Also, the combination conferred a –4.4 (95% CI, –8.15 to –0.65)-point improvement in quality of life on the Dermatology Life Quality Index compared with antihistamines alone, although based on low certainty of evidence.

Using a numeric rating system from 0 to 3, for which lower scores were better, the combination also conferred a –0.25 (95% CI, –0.39 to –0.1) improvement in itch and –0.25 (95% CI, –0.41 to –0.08) improvement in wheal count, both with high certainty of evidence.

Lastly, moderate certainty of evidence showed that the combination led to a reduction in patients experiencing any adverse event, with an absolute effect of 54 per 1,000 patients compared with 67 per 1,000 patients using antihistamines alone, for a difference of 13 fewer patients (95% CI, –29 to 10) and a risk ratio of 0.8 (95% CI, 0.56-1.15).

“So, with moderate certainty of evidence, these add-on LTRAs probably have little to no difference on adverse events compared to H1 antihistamines,” Rayner said. “Unfortunately, we also did not identify any randomized controlled trials that were looking or reporting on these serious neuropsychiatric adverse events ... so the impact of these add-on LTRAs on these serious neuropsychiatric adverse events in urticaria is still very uncertain.”

Still, these results should prompt an update to the AAAAI/ACAAI Joint Task Force guidelines, he added.