Combining LTRAs with antihistamines moderately reduces urticaria severity, potentially improves quality of life, and likely does not increase overall adverse events in people with chronic urticaria compared to using antihistamines alone.

A systematic review and meta-analysis aimed to investigate the use of add-on leukotriene receptor antagonists (LTRAs) for chronic urticaria.

In the pursuit of establishing guidelines for the 2024 AAAAI/ACAAI JTFPP CU, a comprehensive search was conducted across various databases, including Wanfang, VIP, CNKI, CBM, ICTRP, CENTRAL, Embase and MEDLINE. The focus was on randomized controlled trials (RCTs) comparing the combination of LTRA and antihistamines to the use of antihistamines alone for chronic urticaria.

Random effects meta-analyses were performed to address quality of life (QoL; assessed using the Dermatology Life Quality Index [DLQI] scale from 0 to 30, with lower scores indicating better outcomes), itch and hive severity (measured on the numerical rating scale [NRS] scale from 0 to 3, with lower scores indicating better outcomes), urticaria (itch and hives combined; UAS7 scale ranging from 0 to 42, with lower scores illustrating improved outcomes), and adverse events (AEs). With the aid of the GRADE approach, the evidence certainty was determined.

Overall, 3,364 citations and 33 RCTs, involving 3,168 volunteers with a mean age of 36.2 years were identified. Of these trials, one specifically addressed Zafirlukast, and 32 focused on Montelukast. Based on high certainty evidence, it was found that the addition of LTRAs resulted in a reduction in the severity of urticaria (mean difference [MD]: -5.17), itch (MD: -0.25), and hives (MD: -0.25).

In contrast, evidence of lower certainty suggested that using add-on LTRAs may potentially enhance QoL, with an MD of -4.40. Regarding AEs, the relative risk was 0.80 with moderate certainty, indicating that there was likely minimal to no difference in AEs between the groups. Notably, none of the included RCTs addressed neuropsychiatric AEs.

LTRAs + antihistamines show a modest reduction in the severity of urticaria compared to using antihistamines alone. This combination therapy may also contribute to an improvement in QoL for chronic urticaria sufferers and is likely not associated with an overall increase in AEs. These results endorse the adoption of optimal management strategies for chronic urticaria and underscore the importance of updating guidelines accordingly.