Acta Dermato-Venereologica 98-4CompleteContent | Page 15

446 SHORT COMMUNICATION

Advances in dermatology and venereology Acta Dermato-Venereologica

Efficacy of Omalizumab Treatment with Concomitant Antihistamines as Needed for Moderate , Refractory Chronic Spontaneous Urticaria

Eustachio NETTIS 1 , Luca CEGOLON 2 , Luigi MACCHIA 1 , Ippolita ZAZA 1 , Gianfranco CALOGIURI 3 and Elisabetta DI LEO 4 *

1

Department of Emergency and Organ Transplantation , School of Allergology and Clinical Immunology , University of Bari Aldo Moro , Bari ,

2

Scientific Directorate , IRCCS Burlo Garofolo , Trieste , 3 Pneumology Department , Sacro Cuore Hospital , Gallipoli ( Lecce ), and 4 Section of Allergy and Clinical Immunology , Unit of Internal Medicine , “ F . Miulli ” Hospital , Acquaviva delle Fonti , Bari , Italy . * E-mail : elisabettadileo71 @ libero . it Accepted Jan 23 , 2018 ; Epub ahead of print Jan 24 , 2018

Chronic spontaneous urticaria ( CSU ) is a common skin disease defined as spontaneous recurrent wheals and angioedema or both lasting for at least 6 weeks ( 1 ). CSU usually has a duration of 1 – 5 years , but in 14 % of patients it lasts longer ( 2 ). Omalizumab , an anti-IgE humanized monoclonal antibody , has proven effective for the treatment of CSU and is currently recommended as the thirdline treatment option for management of CSU ( 1 , 3 ).

MATERIALS AND METHODS

A prospective observational study was carried out on 24 patients with moderate , H1 antihistamine-refractory CSU , managed at our referral centre since 2015 , who received omalizumab re-treatment after a successful first course of treatment ( i . e . ≥ 90 % improvement in symptoms ) ( 4 ) with this drug . In all patients , re-treatment was necessary because they experienced relapse of the disease with an intensity of symptoms ( urticaria activity score [ UAS7 ] ± 15 %) similar to the pre-treatment period . The option of taking non-sedating second-generation H1 antihistamines ( nsAH ) only as needed for symptomatic relief was investigated , rather than maintaining a stable daily dosage of nsAHs while on omalizumab treatment .

The study comprised a 4-week pre-treatment period , a 24-week first treatment period , an 8 – 16-week follow-up period , and a 24- week second treatment course . Patients were recruited who had moderate , refractory CSU , defined as having a history of spontaneous urticaria for more than 6 weeks , who had not responded to treatment with the approved dosage of nsAH for at least 4 weeks and who had a clinically diagnosed daily urticaria activity score ( UAS ) of 4 or more and a 7-day urticaria activity score ( UAS7 ) between 16 and 27 in the 7 days preceding the first treatment . UAS7 is a widely used patient-reported measure of CSU ( 1 ). Autologous serum skin test ( ASST ) ( 5 ) and measurement of dosage of total serum IgE were performed in all patients at baseline .

Omalizumab was administered subcutaneously every 4 weeks at doses of 300 mg for 24 weeks ( 1 st treatment course ) and again ( 2 nd treatment course ) at least 8 weeks after the end of the first course ( 6 ). Also , in the second treatment course all the patients received omalizumab 300 mg subcutaneously every 4 weeks for 24 weeks .

In the first cycle and between the first and the second cycles , patients continued to receive stable doses of their pre-treatment H1 antihistamine drugs . During the second treatment period the nsAHs were used continuously only in the first 10 days ; thereafter they were administered at 1 dose per day only as needed in the case of mild exacerbations . Patients were allowed to take hydroxyzine 25 mg on demand for relief of symptoms throughout the entire study period , for a maximum of 3 doses per 24 h . Any side-effects of omalizumab were recorded .

The median , range , mean and standard deviation ( SD ) at defined time intervals ( baseline , 12 months , 24 months ) were calculated for all 3 clinical scores ( UAS7 , hive and itch severity score ( ISS )). Comparisons of median scores at 12 and 24 weeks of the latter 3 clinical outcomes with their corresponding baseline values were made using the Wilcoxon non-parametric test . The mean difference between the 3 clinical scores at 12 and 24 weeks and their respective baseline values was calculated using the t-test . Comparisons of proportions were made using the χ 2 test . The level of significance was set at < 0.05 . Statistical analysis was performed with Stata 14 package ( Stata Corporation , College Station , TX , USA ).

The local ethics committee approved the study and written informed consent was obtained from all patients ( registration number : # 5202 ).

RESULTS

For the 24 patients ( 58.3 % ( n = 14 ) women and 41.7 % ( n = 10 ) men ) enrolled in the present study , the mean ± standard deviation ( SD ) age was 48.0 ± 13.7 years . The mean time since diagnosis of CSU was 15.2 ± 11.1 months . ASST was positive in 37.5 % of subjects . The mean IgE level for patients was 161.2 ± 111.0 kU / L . The mean inclinic UAS was 4.6 ± 0.7 and mean ± SD UAS7 19.8 ± 0.5 . The nsAHs administered to the 24 patients were bilastine ( n = 7 ; 29.2 %), cetirizine ( n = 4 ; 16.7 %), fexofenadine ( n = 3 ; 12.5 %), levocetirizine ( n = 2 ; 8.3 %), rupatadine ( n = 2 ; 8.3 %) and ebastine ( n = 6 ; 25.0 %).

Following the first course of treatment , all patients experienced relapse of the disease , with a UAS 7 score similar to the value at pretreatment , within 9 – 19 weeks of the final injection of omalizumab ( mean time to relapse 14.6 weeks ). The mean ± SD UAS7 before starting the second treatment was 21.3 ± 2.7 .

Table I compares the scores of all 3 clinical outcomes ( UAS7 , ISS , hive sore ) at 12 and 24 weeks since the

Table I . Comparison of clinical end-points in the 2 treatment groups

Change

First treatment

Mean dif . ± SD Median ( range )

Second treatment

Mean dif . ± SD Median ( range )

p-value < 0.001 : Wilcoxon test ( hypothesis : median difference < 0 ). Median change ( range ); Wilcoxon nonparametric test , p-value . UAS : urticaria activity score ; ISS : itch severity score ; dif .: difference ; SD : standard deviation . doi : 10.2340 / 00015555-2886 Acta Derm Venereol 2018 ; 98 : 446 – 448

This is an open access article under the CC BY-NC license . www . medicaljournals . se / acta Journal Compilation © 2018 Acta Dermato-Venereologica .