A recent randomized controlled trial shows that patients who do not respond to initial therapy with nonsedating H1-antihistamines might respond to these drugs when given at four-fold higher dosages.
Urticaria is a common dermatological condition that can be acute or chronic. Chronic urticaria (CU) persists for more than 6 weeks and requires frequent healthcare visits, significantly affecting quality of life. Various national and international guidelines recommend using second-generation nonsedating H1-antihistamines (nsAHs) as first-line treatment. However, approximately 60% of CU cases do not respond to first-line treatment. Hence, doctors use various second-line approaches before considering costly third-line treatment with monoclonal antibodies such as omalizumab.
Some common second-line treatment approaches include increasing the dosage of nsAHs by four times, using alternate nsAHs, using combination treatment with multiple nsAHs, and using adjunctive H2-receptor antagonists. Doctors may also use methods like short-term oral corticosteroid therapy. Some methods, like switching to other nsAHs, do not seem to work. Further, the efficacy of a four-fold dose of nsAHs is not fully explored.
This 4-week prospective, randomized, open-label trial aimed to assess the efficacy of four different second-line treatments in patients with CU unresponsive to standard doses of nsAHs. The study was published in the journal Allergy, Asthma & Immunology Research.
Benefits of Increasing nsAH Dosage by Four-Fold Confirmed
The study included 114 patients from two university hospitals in Korea, randomized into four treatment groups: four-fold updosing of nsAHs, multiple combinations of 4 nsAHs (high-dose nsAH groups), switching to other nsAHs, and adjunctive H2-receptor antagonist (standard-dose nsAH groups). The primary endpoint was the urticaria control status after 4 weeks of second-line treatment.
After the treatment period, 43.1% of patients achieved well-controlled urticaria, 36.7% were partly controlled, and 20.2% remained uncontrolled. Significant differences in urticaria control status were observed among the four treatment groups, with the high-dose nsAH group showing a significantly higher proportion of well-controlled cases than the standard-dose nsAH group (51.9% vs. 34.5%, respectively).
Complete symptom control (urticaria activity score over 7 days (UAS7) = 0) was achieved in 20.4% of patients, and the nsAH updosing group showed a higher rate of complete control than the combination treatment group (P = 0.030). However, no significant difference was noted between the high- and standard-dose groups.
All treatment groups showed significant improvement in CU-related patient-reported outcomes, including the UAS7, scores on the Korean version of the urticaria control test (K-UCT), chronic urticaria-specific quality of life (CU-QoL) scores, and visual analog scale (VAS) scores. Logistic regression analysis identified the K-UCT score as significantly associated with well-controlled urticaria, indicating that lower initial symptom burden was associated with a well-controlled state.
The Bottom Line
In conclusion, the study suggests that the use of high-dose (four-fold) nsAHs, via updosing or combination therapy, may be more effective than standard-dose nsAHs for achieving well-controlled urticaria in patients unresponsive to standard doses. In the study, nsAH updosing demonstrated a higher rate of complete symptom control compared to combination therapy. These findings confirm the efficacy of nsAH updosing when standard treatment fails.
Source:
Kim, M., Choi, J. H., Shin, Y. S., Park, H., & Ye, Y. (2023). Efficacy of Second-Line treatments in chronic urticaria refractory to standard dose antihistamines. Allergy, Asthma & Immunology Research, 15(4), 496. https://doi.org/10.4168/aair.2023.15.4.496
