Jiaci

Omalizumab Response Profile and Management

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

doi: 10.18176/jiaci.0323

342

biologics [39], although it is also important to consider their

cost. In this context, data on the relative value of high-dose

antihistamines compared with alternative treatments should

be clear and rigorous. Given the proven efficacy and safety

of omalizumab, it is our expert opinion that clinicians should

consider using this medication to shorten and simplify

the gradual treatment approach that is typically used in

antihistamine-refractory CSU patients [13].

Omalizumab for Treatment of CSU

The efficacy and safety of omalizumab for the treatment

of CSU has been demonstrated in several phase 3 pivotal

trials, namely, ASTERIA I [14], ASTERIA II [3], and the

GLACIAL trial [15,40] (Supplementary Material, Table 2).

The improvements observed in all efficacy variables at

week 12 were still present at week 24 in the ASTERIA I and

GLACIAL trials [14,15]. Overall, the findings from these trials

support the efficacy of omalizumab over 6 months.

Pivotal trials also confirm the favorable safety profile of

omalizumab. The authors found that the incidence rate for

adverse events, the severity of those events, and the incidence

of serious adverse events were all similar in the treatment

group (regardless of the omalizumab dose) and placebo

group [3,14,15].

Importantly, in real-world observational studies, the

efficacy and safety of omalizumab in CSU patients was

similar or even better than in pivotal trials [20,21,41-43]. Of

particular interest is the retrospective, descriptive analysis

of 110 CSU patients treated with omalizumab at 9 Spanish

hospitals [1]. The authors found that 81.8% of patients had a

complete or significant response to treatment, with only 7.2%

not responding to treatment. Moreover, 60% of the patients in

that study remained asymptomatic while receiving omalizumab

alone (that is, they were able to discontinue antihistamine

therapy), and no serious adverse events were reported.

Predictors of Response to Omalizumab

It would clearly be beneficial, if possible, to identify the

clinical predictors of response to omalizumab. Knowledge

of these predictors would also enable physicians to provide

patients with more accurate information about the expected

course of the disease. The findings of the 3 aforementioned

pivotal trials show that the response pattern is dose-dependent.

Thus, the standard dose of 300 mg/4 wk results in a higher

percentage of complete response (UAS=0) or good response

(UAS≤6); moreover, higher doses resulted in faster response

and more sustained disease control [44]. In the pooled analysis

of the trials, disease control was good (UAS7 ≤6) or complete

(UAS7=0) in 58% and 40% of patients, respectively, 12 weeks

after administration of 3 × 300 mg doses of omalizumab [40].

However, disease control was not achieved in all patients

over that period. An analysis of the 3 pivotal trials revealed

that of the patients with uncontrolled urticaria (UAS7 ≤6) at

week 12, 58% subsequently achieved disease control between

weeks 13 and 24 [44]. The mean number of weeks necessary to

obtain a score ≤6 or 0 on the UAS7 was, respectively, 6 weeks

and 12-13 weeks. These data show that some patients respond

quickly to omalizumab, whereas others respond more slowly.

Patients who respond within 4-6 weeks could be classified as

"fast responders" and those requiring 12-16 weeks of treatment

could be considered "slow responders" [45] (Table 2).

According to a recent study [43], the predictors of a

favorable response to omalizumab are as follows: (

) diagnosis

of CSUwith chronic inducible urticaria, (

) no prior treatment

with immunosuppressive drugs, (

) older age, (

) shorter

duration of symptoms, (

) absence of angioedema, and (

)

negative histamine release test. Over 85% of patients who

present these characteristics achieve a complete response to

treatment. In addition, a negative histamine release test result

and absence of angioedema both predict a good response

to omalizumab and correlate with previous trial results

showing that a positive autologous serum skin test (ASST)

result is associated with a longer duration of and more severe

CSU [46,47]. In addition, patients in whom angioedema is a

significant component of urticaria tend to relapse faster after

treatment is discontinued [10]. Neither the patient’s gender nor

their smoking habits have been shown to influence the efficacy

of omalizumab [43]. Asignificant reduction in D-dimer values

following treatment with omalizumab in patients with elevated

baseline D-dimer levels has also been shown [48].

Deza et al [49] recently demonstrated the predictive

value of baseline basophil expression of high-affinity IgE

receptors (FcεRI) for response to omalizumab. The authors

found that FcεRI expression levels in CSU patients are usually

significantly higher than in healthy controls. Moreover,

after the first treatment with omalizumab, FcεRI expression

levels drop immediately, while UAS7 scores decrease and

UCT scores rise. Deza et al observed that baseline FcεRI

expression with a mean fluorescence intensity of less than

4743 in peripheral blood basophils is a significant predictor

of nonresponse to omalizumab (100% sensitivity and 73.2%

specificity).Another study showed that the baseline expression

level of FcεRI was lower in slow responders than in fast

responders [50]. Gericke et al [51] recently reported a slower

response to omalizumab in patients with a positive result in the

ASST or basophil histamine release assay, thus suggesting that

patients presenting with anti-IgE or anti-FcεRI IgG respond

more slowly than those presenting with IgE autoantibodies

against autoantigens (eg, TPO, IL-24) [51].

Table 2.

Patient Profile According to the Response to Omalizumab

Fast responder

Patient who responds in 4-6 weeks

Slow responder

Patient who responds in 12-16 weeks

Complete responder – Sustained UAS7 score = 0

– Absence of symptoms

– Absence of angioedema

– Requires neither salvage medication

nor H

- antihistamines

Good responder

– Sustained UAS7 score = 1-6

Partial responder

– Partial improvement in baseline

UAS7, with scores ranging from 7-15

Nonresponder

– No change in baseline UAS7 score

and sustained scores >16

Abbreviations: UAS, Urticaria Activity Score; UAS7, Urticaria Activity

Score 7.