Jiaci

Omalizumab Response Profile and Management

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

doi: 10.18176/jiaci.0323

340

definitions would help to guide the medical management of

patients in accordance with their individual response profile.

In this context, an expert working group comprising

specialists with broad experience in treating urticaria was

convened to define CSU patient profiles depending on the

varying responses to omalizumab. We describe these profiles

and provide a clear, straightforward therapeutic algorithm to

guide the management of patients with CSU according to their

specific response to omalizumab.

Methods

We report the consensus opinions of a group of experts

in urticaria treatment. The group comprised allergists and

dermatologists in Spain with expertise in treating urticaria.

This working group met 3 times from 2015 to 2016 to discuss

the main unresolved issues regarding therapeutic management

of CSU patients.

Initially, the group generated a series of unresolved

questions about the optimal use of omalizumab for the

treatment of CSU patients that commonly arise in routine

clinical practice. The 3 main questions raised were as follows:

(

) What criteria are taken into consideration when urticaria

is “controlled”? (

) Can we identify specific patient profiles

based on individual differences in the response to omalizumab?

(

) What is the optimal therapeutic strategy for each of these

profiles?

To answer these questions, we performed a bibliographic

review of publications on urticaria in the MEDLINE

database. Using the PubMed search engine, we searched for

various combinations of the following key words in English:

Management, Disease, Urticaria, Chronic Spontaneous

Urticaria, Guidelines, Prevalence, Treatment, Therapy,

Omalizumab, Antihistamines, Refractory, Cyclosporine,

Responders, Non-responders, Activity, UAS, UAS7, QoL,

Control, Algorithms, Response predictors, Questionnaire

and

Impact

Questions that were not fully addressed in the literature

were addressed based on the extensive clinical experience of

the team of experts. Prior to the meetings, the experts were

asked to individually prepare their responses to the 3 main

study questions in order to facilitate the group discussions.

The therapeutic protocol and patient profiles defined in this

document are based on available published scientific evidence

in conjunction with the consensus expert option of this group

of specialists. In addition, a consensus summary of the key

points was also developed.

The discussions held to address the aforementioned

unresolved issues also yielded several other omalizumab- and

CSU-related questions. These issues are addressed in this

document.

Discussion

Measurement of the Activity and Impact of CSU

In many cases, it is difficult to precisely assess CSU

owing to the heterogeneous nature of the condition and the

evanescence of the skin lesions. For this reason, clinical

guidelines recommend the use of grading scales in routine

clinical practice, and several validated tools are available to

monitor disease activity and control and to assess the impact

of the condition on patient QOL [2,10]. While it is important

to use these scales for the initial assessment, they should also

be used for follow-up purposes after initiation of treatment.

The scales are particularly useful in patients with poor disease

control despite good adherence to treatment. By contrast,

these scales may be unnecessary in stable, well-controlled

patients [2].

By measuring disease activity, control, and impact, the

clinician can identify the patient’s individual clinical profile

and determine whether his/her CSU is under control. The

resulting scores can be used to guide selection of treatment in

accordance with the patient's disease status [2].

The UrticariaActivity Score (UAS), particularly the UAS7

version, is recommended for assessment of the symptoms

of CSU [2,24]. The UAS7, which was validated in 2008

to measure urticaria symptoms, defines 5 “disease activity

categories” according to the score obtained (Supplementary

Material, Table 1) [25]. The Spanish versions of the UAS

and UAS7 were both recently validated in the EVALUAS

trial for use as diagnostic and follow-up tools for patients

with CSU [26]. Note, however, that the UAS7 is not suitable

for evaluating the activity of chronic inducible urticaria or

angioedema. TheAngioedemaActivity Score is used to assess

isolated or CSU-associated angioedema [27].

The consensus opinion of the present expert group is that

the Urticaria Control Test (UCT) is the best currently available

tool for quantification of disease control in all types of chronic

urticaria (which includes both CSU and inducible forms of

urticaria). The patient's current treatment should be considered

when using these scales, otherwise the scores would not be

comparable at different time points.

When evaluating the overall status of a patient with CSU,

it is essential to assess the impact of the disease on QOL [2,10].

To date, the only questionnaire specifically developed to

measure QOL in CSU patients is the Chronic Urticaria Quality

of Life Questionnaire [28].

We recommend using the UAS7 to evaluate the activity

of CSU, given that this instrument has proven its value in

numerous clinical trials and studies; moreover, the members

of this expert group have successfully used this tool for many

years. The UAS7 questionnaire is a self-reported instrument

that correlates well with the Dermatology Life Quality Index,

which is commonly used to assess QOL in dermatology

patients [29-31]. Ideally, the UAS7 should be administered

weekly to monitor treatment response. It is advisable to use

the UCT concomitantly with the UAS7 to ensure that patients

have completed both of these instruments correctly during the

consultation.

Definition of a Well-Controlled CSU Patient

To accurately determine disease control during follow-up,

it is essential to first establish a clear definition of qualitative

control to permit the specialist to evaluate response to treatment

in daily clinical practice. Moreover, such a definition is

important in order to facilitate reliable comparisons of clinical

trials.