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.