UCREX is an observational, multicenter, and prospective study (12 months) conducted in Spain between May 31st, 2013 and January 31st, 2015. 39 hospitals and 42 investigators (21 dermatologists and 21 allergists) participated in the study. Patients were aged ≥18 years, with de novo or established CSU or CINDU diagnosis, and attended at allergy or dermatology services. Patients with acute urticaria, urticarial vasculitis or other type of physical urticaria not associated with CU or angioedema without wheals or pruritus related to cutaneous diseases or participating in any other study were excluded.

The study was structured in four visits (baseline visit, and at 3, 6 and 12 months). Basic study data was recorded by an ad-hoc electronic Case Report Form (eCRF). Patient reported outcomes (PROs) were recorded through physical questionnaires and transferred to the study database. Data collection referred to daily clinical practice was based on clinical charts and the following completed by study questionnaires: Urticaria Activity Score (UAS) and UAS over 7 days (UAS7) to assess key urticaria signs and symptoms; Chronic Urticaria Quality-of-Life Questionnaire (CU-Q2oL) and EuroQol-5 dimensions (EQ-5D) to evaluate impact on QoL; Medical Outcomes Study Sleep (MOS-Sleep) Scale to assess disease impact on sleep quality and Hospital Anxiety and Depression Scale (HADS) to measure levels of hospital anxiety and depression (Fig. 1).9

Figure 1.

Study design from the selection period to the follow-up period.

*HADS, HRQoL (CU-Q2oL, EQ-5D), MOS-Sleep, sociodemographic and anthropometric data, clinical characteristics of urticaria, associated comorbidities, direct resources used due to CU, previous referral circuit, days of work absenteeism, time from the onset of symptoms to diagnosis of CU.

Abbreviations: CU, chronic urticaria; CU-Q2oL, Chronic Urticaria Quality-of-Life Questionnaire; EQ-5D, EuroQol-5 dimensions; HADS, Hospital Anxiety and Depression Scale; HRQoL, Health-Related Quality-of-Life; MOS-Sleep, Medical Outcomes Study Sleep Scale; UAS, Urticaria Activity Score; UAS7, Urticaria Activity Score over 7 days; V, visit.

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Secondary variables included: sociodemographic and clinical data, associated comorbidities, disease management, treatment patterns, direct healthcare resources and PROs. CU-Q2oL and EQ-5D questionnaire was used to evaluate symptoms and impact of CU on QoL.10–12 To assess disease impact on sleep quality, MOS-Sleep scale was used.13,14 The HADS questionnaire measured levels of hospital anxiety and depression.15,16

The main study variables were UAS and UAS7. To collect the direct healthcare resources associated with CU, the number of hospital admissions, visits to primary care (PC), emergency, allergology and dermatology services, diagnostic tests performed before and during the study and prescribed treatments were analyzed.

Sample size estimation was based on a 0.6% CU prevalence in Spain4 and an accuracy of 5.5%, estimating a maximum uncertainty proportion and greater variability of 50% and a confidence interval of 95% and considering 5% of losses. An estimated 335 patients were considered as a representative sample size for the study.

Statistical analyses were carried out in evaluable patients and descriptive analyses of all variables were carried out separately, using tables of absolute and relative frequencies for discrete qualitative and quantitative variables, and by means of average statistics, standard deviation (SD), extreme values ​​and quartiles for continuous quantitative variables. For all comparisons a statistical significance level of 0.05 was considered. Statistical package Statistical Analysis System (SAS) version 9.2 or later for Windows was used.

The study was carried out following the ethical principles of the Declaration of Helsinki and the guidelines specified in Order SAS/3470/2009 of the Spanish Agency of Medicines and Medical Devices (AEMPS). Protocol, informed consent form and other information for the patients were approved by the reference Clinical Research Ethics Committee (CEIC) of Hospital del Mar (IMIM of Barcelona), as well as all the CEICs and autonomous communities of the participating hospitals, as needed. All patients signed a written informed consent before being included in the study.

Baseline sociodemographic and clinical characteristics of the study population are collected in Table 1.The patients included in the study had a mean age (SD) of 46.6 (14.2) years, were mainly female (71.8%) and 152 (42.1%) patients showed angioedema in any of the episodes/outbreaks of urticaria. Most patients (n = 345; 95.6%) were diagnosed with CSU, being associated to CINDU in 38.6% of cases. Only 16 patients (4.4%) were diagnosed with CINDU (not associated with CSU). Among the 361 patients included in the study, 199 were actively working (55.1%) (Table 1). Within these active patients, 195 (98.0%) presented absenteeism during the year prior to inclusion and 147 (73.9%) during the 12 months of the study, with a mean (SD) of 2.7 (17.5) and 4.8 (37.4) days, respectively.

In the study, 75.6% of the CU patients were symptomatic (UAS7 >0) at the 12-months visit despite being treated according to daily clinical practice. Among patients who responded to the questionnaires (N = 176), the incidence of wheals and/or pruritus was tended to reduce according to the UAS scale between baseline and the 12-months visit (117 [66.5%] and 131 [74.4%] patients with wheals and pruritus, respectively, at baseline vs 58 [33.0%] and 80 [45.5%] patients at the 12-months visit, respectively). Mean (SD) UAS and UAS7 scores also tended to decrease throughout the study (2.6 [2.0] and 14.3 [11.0] at baseline vs 1.1 [1.5] and 8.6 [9.7] at 12 months, respectively). Although UAS and UAS7 score reductions were related to symptom improvement, the severity of the disease in these patients at the 12-months visit was categorized as moderate for 22 patients (12.5%) and as intense for seven patients (4.0%) (Fig. 3)

Figure 3.

Descriptive of CSU activity by visit stratified by wheals, pruritus, UAS and UAS7 mean scores by visit.

Wheals (A), pruritus (B), UAS (C) and UAS7 (D) mean scores by visit.

Evaluable population (N = 176).

Mild pruritus: pruritus present but not irritating or annoying; moderate pruritus: annoying itching but without interfering with patient’s daily activities or with patient’s sleep; intense pruritus: severe itching, annoying enough to interfere with patient’s daily activities and with patient’s sleep.

Abbreviations: CSU, chronic spontaneous urticaria; h, hours; UAS, Urticaria Activity Score; UAS7, Urticaria Activity Score over 7 days.

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Disease management of the CU patients was considered from the year prior to study inclusion until the 12-months visit. During the year prior to inclusion, emergency services had a mean (SD) of 1.6 (2.8) visits due to CU (n = 355), tended to reduce by 0.3 (1.3) during the 12 months of the study (n = 268). Hospitalization was rarely needed during the year prior to study inclusion (n = 357; mean [SD] of 0.0 [0.1]) and during the 12 months of the study (n = 268; mean [SD] of 0.0 [0.2]). PC was the management reference during the year prior to inclusion (n = 340), with a mean (SD) of 3.6 (6.8) visits (vs allergology and dermatology [n = 358 in both cases], with 2.4 [4.3] and 2.6 [4.2] visits, respectively). CU patients were initially identified in PC centers (294 patients, 81.9%) and subsequently tendency of patients being referred to dermatology services (155 patients, 42.9%) was higher than allergy services (139 patients, 38.5%) for diagnosis confirmation and monitoring. After being referred to specialists, CU patients had a mean (SD) average of 1.7 (3.3) follow-up visits to allergy services and 1.4 (2.8) to dermatology services per year.

Diagnostic tests were conducted in 328 (95.1%) of CSU patients, being blood count the most commonly used (323 patients, 93.6%). Extension tests were also performed in 286 patients (82.9%) (Table 2). Regarding CINDU patients (n = 16), 14 patients (87.5%) had undergone diagnostic tests at inclusion, and provocation tests has the tendency to be the most frequents (11 patients, 68.8%) (Table 3).

Trends of dermatology and allergology specialists (n = 164 and n = 189 patients, respectively) were detected in the routine tests of patients with CSU performed in the study. At baseline visit, more number of diagnostic tests were tended to be performed by allergology services (n = 788, 55.3%) than dermatology (n = 637, 44.7%) (Table 4). Among CINDU patients, routine tests and provocation tests were carried out for 26 (15.9%) and 28 (17.1%) patients in dermatology services, respectively, and 47 (24.9%) and 26 (13.8%) patients in allergy services at baseline visit, respectively.

During the 1-year UCREX study in Spain, NS-H1AH (336 patients, 47.6%) was tended to be the most frequently prescribed treatments for CU patients (n = 706), followed by sedating H1-antihistamines (S-H1AH) (99 patients, 14.0%), omalizumab (91 patients, 12.9%) and corticosteroids (80 patients, 11.3%) (Fig. 4). Omalizumab prescription was present along the 1-year UCREX study. The trend of omalizumab prescriptions were mostly at the beginning of the study (44 prescriptions at baseline), although they also occurred in subsequent visits (24, 8 and 12 prescriptions at 3-, 6- and 12-months visits, respectively) (Fig. 4).

Figure 4.

Treatments prescribed to CU patients in Spain throughout UCREX study and Omalizumab prescription during the study.

Treatments prescribed to CU patients (A), Omalizumab prescription (B).

Evaluable population (N = 361). A patient may have taken treatments from different treatment families. Treatments could be concomitants and/or sequential.

Abbreviations: H2AH, -antihistamines; LTRA, leukotriene receptor antagonists; NSAID, non-steroidal anti-inflammatory drugs; NS-H1AH, non-sedating H1-antihistamines; S-H1AH, sedating H1-antihistamines.

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CU patients reported a CU-Q2oL mean score (SD) of 24.1 (17.0) at baseline visit (n = 336) and 13.9 (15.0) at 12-months visit (n = 254), showing pruritus as the main negative impact (46.4 (30.3) and 23.2 (23.2), respectively) (Fig. 5). According to EQ-5D questionnaire, at baseline visit (n = 357) 212 CU patients (58.7%) referred pain/discomfort, 179 patients (49.6%) anxiety/depression, 90 patients (24.9%) impact on daily activities and 61 patients (16.9%) referred mobility problems. These percentages remained stable, except for pain/discomfort and anxiety/depression, which tended to decrease at 12-months visit (n = 266: 107 [29.6%] and 97 [26.9%] patients, respectively). Mean VAS score (SD) was 68.4 (20.4) at baseline visit (n = 355), which tended to increase by 73.6 (19.6) at 12-months visit (n = 266). Index score remained stable during the study (0.8 [0.2]) (n = 357 at baseline and n = 266 at 12-months visit) (Appendix A1).

Figure 5.

Questionnaire CU-Q2oL results per visit.

Evaluable population (N = 361).

Abbreviations: CU-Q2oL: Chronic Urticaria Quality-of-Life questionnaire.

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MOS-Sleep questionnaire established that CU had a negative impact in sleep quality, and this trend was barely improved with the treatment. Patients slept a mean (SD) of 6.4 (1.4) hours per night at baseline visit (n = 331) and 6.6 (1.2) at 12-months visit (n = 236). The trend of mean scores for the different dimensions hardly improved throughout the study (Fig. 6).

Figure 6.

MOS-Sleep questionnaire results per visit.

Evaluable population (N = 361).

MOS-Sleep scores have been transformed so that they present values from 0 to 100 in such a way that 0 would be the worst situation and 100 the best.

Abbreviations: MOS-Sleep, Medical Outcomes Study Sleep Scale.

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Anxiety and depression levels according to HADS scale remained steady during the 1-year UCREX study. Anxiety mean (SD) value went from 8.7 (4.5) at baseline (n = 349) to 7.0 (4.3) at 12-months visit (n = 262), while mean (SD) depression value went from 5.1 (4.4) (n = 345) to 4.7 (4.3) (n = 261), respectively.