The Efficacy And Safety Of Long-term Combined Use Of Second-generation Antihistamines In The Treatment Of Chronic Spontaneous Urticaria

Objective:We followed up the treatment and prognosis of patients with chronic spontaneous urticaria（CSU）,then retrospectively evaluated the short-term and long-term efficacy and safety of the combinations of second-generation H₁-antihistamines（sgAHs）in CSU.Methods:A total of 75 patients diagnosed as CSU in our department from 2018 September to2019 December were enrolled in this retrospective study.Demographic,clinical and laboratory datas were recorded,physical examinations and laboratory tests as performed on the patients upon their first visit and an urticaria activity score for one day（UASday）was recorded at this time.All enrolled patients received licensed doses of sgAHs as the first-step treatment but their symptoms could not be controlled completely,2-4 sgAHs combinations regimen comprised second-step treatments.If complete control was not achieved,H₂-antihistamines（ranitidine or famotidine）and/or montelukast were added sequentially as third-step treatments.Oral administration of tripterygium wilfordii polyglycoside（TWP）and subcutaneous omalizumab were used as a fourth-step treatment.Once complete control was achieved,the treatment regimen was continued for at least 2 months.Doses of the sgAHs or other medications were then tapered every 3 to 4 weeks until all medications were discontinued.The early end points for evaluating disease activity was classified as complete control（UASday=0）,partial control（1≤UASday≤the baseline UASday）,uncontrol（UASday unchanged or increased）.The late end-points of disease control was to observe the medication of patients at 52 weeks,which was classified as being in complete remission（CR）off therapy or CR on therapy,then evaluate the long-term efficacy and safety of the combinations of sgAHs.Results:Among the 75 patients,28 were male and 47 were female.The mean age of onset was 41.8±12.3 years.The median disease course was 4 months.There were 35（46.7%）,34（45.3%）,3（4.0%）completely controlled with second-,third-,and fourth-step treatments respectively,3（4.0%）were under partial control.In the 35 patients completely controlled by second-step treatment,9 were treated by the combination of two sgAHs,18 by three sgAHs,8 by four sgAHs.In the 34 patients completely controlled by third-step treatment,10 were treated by the addition of H₂-antihistamines,5 by montelukast,and 19 by both.In the3 patients completely controlled by fourth-step treatment,2 received omalizumab and 1received TWP.The addition of H₂-antihistamines and/or montelukast significantly decreased the number of wheals and reduced UASday scores by an average of 1 point within 1-2 week.At week 52,51 patients（68.0%）were in complete remission（CR）off therapy and 21（28.0%）in the CR on therapy state.UASday（P=0.024,OR=3.16,95%CI:1.92-5.78）was an independent risk factor for long-term maintenance therapy of CSU.During the treatment,somnolence was the most common adverse effect of sgAHs and were seen in 25（33.3%）.There were no serious adverse reactions in combination with sgAHs.Conclusion:Multi-sgAH combinations show definite short-term and long-term efficacy and acceptable safety in the treatment of patients with CSU.Patient were well tolerated.H₂-antihistamines and montelukast further enhance the efficacy of combinational sgAHs without compromising safety.UASday was an independent risk factor for long-term maintenance therapy of CSU.