Jiaci

Giménez Arnau AM, et al.

J Investig Allergol Clin Immunol 2019; Vol. 29(5): 338-348

doi: 10.18176/jiaci.0323

According to the EAACI/GA2LEN/EDF/WAO guidelines,

the aim of treatment in CSU is to achieve complete control

of signs and symptoms while ensuring patient safety and

QOL [2]. Several scales are available to monitor the variations

in different aspects of the disease (Table 1), and a "good"

clinical course could be defined based on any of the following:

UAS7 activity index <6; a decrease >90% on the UAS7: UCT

score >12; or the clinical course based on the clinical criteria

of the treating physician.

Given the lack of a specific recommendation regarding the

optimal evaluation scale, we believe that a patient whose CSU

activity is "well-controlled” should be defined as a stable UAS7

score ≤6 that is sustained over time. Importantly, a UAS7 score

≤6 is closely correlated with the QOL index [32,33].

No clinical trials have yet been performed to establish

precisely how long the patient needs to maintain a UAS7 <6

to be considered in remission. Management is patient-specific,

both in regard to the type and duration of treatment. Likewise,

the best approach to treatment discontinuation (ie, sudden

termination or gradual tapering) has not yet been determined.

Antihistamine-Refractory Patients

The activity of CSUmay fluctuate between low- and high-

activity periods, when the condition is considered severe. Even

when the maximum accepted antihistamine dose is prescribed,

this is insufficient to control the clinical manifestations of CSU

in a substantial proportion of patients (63%) [11]. The UCREX

trial [34] showed that more than 75% of CSU patients remain

symptomatic even after 6 months of antihistamine treatment.

Likewise, the REG-MAR trial [12], carried out in a cohort of

549 CSU patients, showed that 77.3% were refractory to H

antihistamines at the licensed dose. Importantly, antihistamine

treatment can exacerbate urticaria, although this reaction

is rare [35,36]. However, these data should be interpreted

taking into account the fact that patients with CSU in these

studies, who were seen mostly at tertiary centers, do not

necessarily represent the general population of patients with

the disease. Most CSU patients who respond properly to a

second-generation antihistamine at a licensed dose prescribed

by their family doctor probably do not attend specialized units

in urticaria.

CSU has a major negative impact on QOL and health care

costs [7,8]. The recentASSURE-CSU trial [11] highlighted the

financial burden and negative impact of CSU/chronic inducible

urticaria on health-related QOL in refractory patients. The

results of that study showed that not only did CSU interfere

with QOL, but that it also had both direct (ie, health) costs and

indirect (ie, social) costs.

The favorable safety profile of most second-generation

antihistamines means that these drugs can be used as second-

line therapy at doses higher than the licensed doses [2,37]. A

recently published meta-analysis and systematic review [13]

found that 63.3% of CSU patients who did not respond to the

licensed dose of H

antihistamines responded well to higher

doses. Furthermore, the increased dose significantly improved

control of wheals and itching in the 49% of patients who

required a dose increase.

Nevertheless, there is no effective method to predict

whether an antihistamine will have a beneficial clinical

effect or not. A recent study showed that measurement of the

histamine-induced wheal can predict which patients will have

a strong clinical response to antihistamines, although its utility

for identifying nonresponders is limited [38].

The off-label indication for antihistamine dosing

should be revised in light of the availability of new, highly

effective treatments such as omalizumab and other emerging

341

Table 1.

Activity, Control, and Quality of Life Scales for Urticaria and Angioedema Patients

Activity UAS7 – Patients with wheals

– Exact clinical picture of the

– Prospective PRO measure

measure AAS – Patients with wheals

current frequency and

– Patient must complete daily

and angioedema

severity of the CSU

(not always feasible)

– Patients with

symptoms (daily evaluation,

– Valid only for patients with CSU, not for

angioedema

weekly score)

patients with CIndU

– Has been validated for use in adults only

Control

UCT – Patients with wheals,

– Retrospective PRO measure

– The information is not well explained

measure

angioedema, or both

– Short and simple structure

– Simple scoring system

– Results available immediately

after completion

– Can be applied to all the forms

of CU

QOL CU-Q2oL – Patients with wheals

– Validated in many languages

– Slight variations among versions in

measure

or with wheals and

– Good validity and reliability

different languages

angioedema

level

– Applicable to CSU but not to CindU

– Good sensitivity to change

– Comparatively complicated scoring

system

– Not perfectly adapted to CSU patients

in whom angioedema predominates

Abbreviations: AAS, Angioedema Activity Score; CIndU, chronic inducible urticaria; CSU, chronic spontaneous urticaria; CU, chronic urticaria; CU-Q2oL,

Chronic Urticaria Quality of Life Questionnaire; PRO, patient-reported outcome; QOL, quality of life; UAS, Urticaria Activity Score; UAS7, Urticaria

Activity Score 7; UCT, Urticaria Control Test.