Jiaci

Giménez Arnau AM, et al.

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

doi: 10.18176/jiaci.0323

Even though omalizumab generally provides an early

benefit [3,14,15], some patients have a delayed response, often

only after 12 weeks of treatment [14,44]. This finding suggests

that if fewer than 3 treatments (300 mg/4 wk) are administered,

the opportunity to achieve symptom control in a nonresponder

(UAS7 ≤6) could be lost [44].

Prediction of symptom return after stopping omalizumab

was recently addressed in a study that analyzed data

from 2 clinical trials, including 642 patients [52]. The authors

studied the predictive potential of 746 variables, which

included baseline patient characteristics and disease measures

(ie, start of treatment), such as IgE levels, weekly urticaria

activity score (UAS7), and pre- and postbaseline medications.

Only 2, variables, UAS7 and the speed of response to

treatment, predicted speed of symptom return. The results

suggest that patients with worse symptoms before treatment

(ie, higher UAS7 score) and a slow response to omalizumab

have a higher probability of rapid symptom return after

discontinuation of treatment. In contrast, those with a lower

UAS7 score at baseline and fast response to omalizumab have

a lower probability of rapid symptom return.

Therapeutic Strategy According to the

Patient’s Response Profile

Defining patient profiles according to the response to

omalizumab would have 2 main benefits: first, it would

facilitate medical management of the patient, and second, it

would improve treatment selection, thus enabling the clinician

to select the most appropriate therapeutic plan based on the

individual's response profile. Unfortunately, to date, no such

categorization has been reported in the published literature.

CSU patients can be either fast or slow responders to

omalizumab [44,51]. Available evidence for slow responders

indicates that omalizumab should be continued for 24 weeks

to obtain a sustained favorable response (UAS7≤6) over

time [44]. In patients with severe disease (ie, UAS7>28 with

unbearable symptoms), the therapeutic schedule could be

modified prior to administration of the sixth dose.

Based on our clinical experience and the literature review

we conducted for this study, we recommend classifying patients

into 1 of 4 different response profiles—nonresponders, partial

responders, good responders, and complete responders—

depending on their response to omalizumab (300 mg/4 wk)

after the first 3 and 6 months of treatment [33]. Based on this

classification system, we also propose a specific therapeutic

approach for each response profile.

The 4 different approaches mainly involve modification

of the omalizumab dose or a change in the treatment

interval [33,45]. Dose increases or reductions should be

stepwise. Thus, a standard dose of 300 mg/4 wk should be

increased to 450 mg/4 wk [33,53-55] and then, if necessary,

up to 600 mg/4 wk [33,56]. In cases requiring dose reduction,

the dose would be reduced from 300 mg/4 wk to 150 mg/4 wk.

According to a study by Curto et al [12] involving

286 patients treated at 15 hospitals under conditions of routine

clinical practice, 16% of patients required their dose to be

increased to 450 mg/4 wk, while 4% required an increase to

600 mg/4 wk to achieve complete disease control. The authors

found that 21% of patients required updosing; in addition,

several factors—body mass index ≥30, age >57 years, and

previous cyclosporine use—were strongly correlated with the

need for updosing to ensure good disease control [12].

The standard dose of omalizumab is 300 mg administered

every 4 weeks; this frequency could be increased to

every 2 weeks at the same dose (300 mg) [3], according to the

criteria of the attending physician. However, the dose interval

should never be longer than 8 weeks, except in cases in which

the medication is being discontinued [57].

If the aim of the therapeutic strategy is to increase the dose

or to shorten the administration interval, the change must first

be tailored to the patient. However, it should be noted that

in most cases—such as in patients in whom the UAS7 score

remains stable over the 4-week period—the recommended

strategy is to increase the dose while maintaining the

administration interval, given that this strategy is supported by

the strongest scientific evidence [56,58]. By contrast, evidence

to support an increase in the administration interval at the same

dose is scant, and the samples in the few available studies are

small [56]. Nonetheless, this strategy may be considered in

certain cases: (

) when the usual strategy (ie, updosing) fails to

produce an improvement; (

) when the symptoms recurrently

worsen and the UAS7 score increases during the 2 weeks

prior to receiving the following omalizumab dose; (

) when

the pattern of response is better during the first 2 weeks after

administration; and (

) when the patient expresses a clear

preference for this strategy.

Although administration of omalizumab at >600 mg has

proven to be safe and effective in asthmatic patients [59], we

suggest that clinicians should not exceed the 600 mg/4 wk dose

owing to the lack of clinical evidence to support this dose in

CSU patients [56].

Likewise, therapeutic strategies based on dose reduction

or shortening of the treatment interval may be combined

successively (never simultaneously), as it is important that

treatment be withdrawn or reduced gradually. Thus, for

example, the dose can first be reduced by 1 step, and then—

provided that the patient's condition remains stable—the same

dose could be administered over longer intervals until the

decision is made to discontinue treatment [3,60].

The 4 different patient profiles defined in this study, which

are based on the individual response to omalizumab at the

standard dose (300 mg/4 wk) after 6 months of treatment, are

described in detail below. Figure 3 shows the recommended

therapeutic approach according to the specific patient profile.

After careful consideration and much discussion about the

advantages of using either the UCT and UAS7 scales or using

the percentage decrease from baseline in the UAS7, we believe

that the UAS7 should be used as the main, but not the only,

indicator of response to omalizumab (Table 2).

4.1. Nonresponders

Patients classified as nonresponders to omalizumab are

those whose baseline UAS7 score remains unchanged after

treatment and who continue to present a UAS7 score >16 after

6 doses of omalizumab at 300 mg/4 wk (Table 2).

Given that some patients are late responders—that is,

only achieving disease control between 13 and 24 weeks after

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