14 CLINICAL STUDIES

14.1 Asthma

Adult and Adolescent Patients 12 Years of Age and Older

The safety and efficacy of XOLAIR were evaluated in three randomized, double-blind, placebo-controlled, multicenter trials.

The trials enrolled patients 12 to 76 years old, with moderate to severe persistent (NHLBI criteria) asthma for at least one year, and a positive skin test reaction to a perennial aeroallergen. In all trials, XOLAIR dosing was based on body weight and baseline serum total IgE concentration. All patients were required to have a baseline IgE between 30 and 700 IU/mL and body weight not more than 150 kg. Patients were treated according to a dosing table to administer at least 0.016 mg/kg/IU (IgE/mL) of XOLAIR or a matching volume of placebo over each 4-week period. The maximum XOLAIR dose per 4 weeks was 750 mg.

In all three trials an exacerbation was defined as a worsening of asthma that required treatment with systemic corticosteroids or a doubling of the baseline ICS dose. Most exacerbations were managed in the outpatient setting and the majority were treated with systemic steroids. Hospitalization rates were not significantly different between XOLAIR and placebo-treated patients; however, the overall hospitalization rate was small. Among those patients who experienced an exacerbation, the distribution of exacerbation severity was similar between treatment groups.

Asthma Trials 1 and 2

At screening, patients in Asthma Trials 1 and 2 had a forced expiratory volume in one second (FEV1) between 40% and 80% predicted. All patients had a FEV1 improvement of at least 12% following beta2-agonist administration. All patients were symptomatic and were being treated with inhaled corticosteroids (ICS) and short-acting beta2-agonists. Patients receiving other concomitant controller medications were excluded, and initiation of additional controller medications while on study was prohibited. Patients currently smoking were excluded.

Each trial was comprised of a run-in period to achieve a stable conversion to a common ICS (beclomethasone dipropionate), followed by randomization to XOLAIR or placebo. Patients received XOLAIR for 16 weeks with an unchanged corticosteroid dose unless an acute exacerbation necessitated an increase. Patients then entered an ICS reduction phase of 12 weeks during which ICS dose reduction was attempted in a step-wise manner.

The distribution of the number of asthma exacerbations per patient in each group during a study was analyzed separately for the stable steroid and steroid-reduction periods.

In both Asthma Trials 1 and 2 the number of exacerbations per patient was reduced in patients treated with XOLAIR compared with placebo (Table 11).

Measures of airflow (FEV1) and asthma symptoms were also evaluated in these trials. The clinical relevance of the treatment-associated differences is unknown. Results from the stable steroid phase Asthma Trial 1 are shown in Table 12. Results from the stable steroid phase of Asthma Trial 2 and the steroid reduction phases of both Asthma Trials 1 and 2 were similar to those presented in Table 12.

Table 11. Frequency of Asthma Exacerbations per Patient by Phase in Asthma Trials 1 and 2
	Stable Steroid Phase (16 wks)
	Asthma Trial 1		Asthma Trial 2
Exacerbations per patient	XOLAIR N=268	Placebo N=257	XOLAIR N=274	Placebo N=272
0	85.8%	76.7%	87.6%	69.9%
1	11.9%	16.7%	11.3%	25.0%
≥2	2.2%	6.6%	1.1%	5.1%
p-Value	0.005		<0.001
Mean number exacerbations/patient	0.2	0.3	0.1	0.4
	Steroid Reduction Phase (12 wks)
Exacerbations per patient	XOLAIR N=268	Placebo N=257	XOLAIR N=274	Placebo N=272
0	78.7%	67.7%	83.9%	70.2%
1	19.0%	28.4%	14.2%	26.1%
≥2	2.2%	3.9%	1.8%	3.7%
p-Value	0.004		<0.001
Mean number exacerbations/patient	0.2	0.4	0.2	0.3

Table 12. Asthma Symptoms and Pulmonary Function During Stable Steroid Phase of Asthma Trial 1
	XOLAIR N=268*		Placebo N=257*
Endpoint	Mean Baseline	Median Change (Baseline to Wk 16)	Mean Baseline	Median Change (Baseline to Wk 16)
Asthma symptom scale: total score from 0 (least) to 9 (most); nocturnal and daytime scores from 0 (least) to 4 (most symptoms).
* Number of patients available for analysis ranges 255-258 in the XOLAIR group and 238-239 in the placebo group. † Comparison of XOLAIR versus placebo (p < 0.05).
Total asthma symptom score	4.3	–1.5†	4.2	–1.1†
Nocturnal asthma score	1.2	–0.4†	1.1	–0.2†
Daytime asthma score	2.3	–0.9†	2.3	–0.6†
FEV1 % predicted	68	3†	68	0†

Asthma Trial 3

In Asthma Trial 3, there was no restriction on screening FEV1, and unlike Asthma Trials 1 and 2, long-acting beta2-agonists were allowed. Patients were receiving at least 1000 µg/day fluticasone propionate and a subset was also receiving oral corticosteroids. Patients receiving other concomitant controller medications were excluded, and initiation of additional controller medications while on study was prohibited. Patients currently smoking were excluded.

The trial was comprised of a run-in period to achieve a stable conversion to a common ICS (fluticasone propionate), followed by randomization to XOLAIR or placebo. Patients were stratified by use of ICS-only or ICS with concomitant use of oral steroids. Patients received XOLAIR for 16 weeks with an unchanged corticosteroid dose unless an acute exacerbation necessitated an increase. Patients then entered an ICS reduction phase of 16 weeks during which ICS or oral steroid dose reduction was attempted in a step-wise manner.

The number of exacerbations in patients treated with XOLAIR was similar to that in placebo-treated patients (Table 13). The absence of an observed treatment effect may be related to differences in the patient population compared with Asthma Trials 1 and 2, study sample size, or other factors.

Table 13. Percentage of Patients with Asthma Exacerbations by Subgroup and Phase in Asthma Trial 3
	Stable Steroid Phase (16 wks)
	Inhaled Only		Oral + Inhaled
	XOLAIR N=126	Placebo N=120	XOLAIR N=50	Placebo N=45
% Patients with ≥1 exacerbations	15.9%	15.0%	32.0%	22.2%
Difference (95% CI)	0.9 (–9.7, 13.7)		9.8 (–10.5, 31.4)
	Steroid Reduction Phase (16 wks)
	XOLAIR N=126	Placebo N=120	XOLAIR N=50	Placebo N=45
% Patients with ≥1 exacerbations	22.2%	26.7%	42.0%	42.2%
Difference (95% CI)	–4.4 (–17.6, 7.4)		–0.2 (–22.4, 20.1)

In all three of the trials, a reduction of asthma exacerbations was not observed in the XOLAIR-treated patients who had FEV1>80% at the time of randomization. Reductions in exacerbations were not seen in patients who required oral steroids as maintenance therapy.

Pediatric Patients 6 to <12 Years of Age

The safety and efficacy of XOLAIR in pediatric patients 6 to <12 years of age with moderate to severe asthma is based on one randomized, double-blind, placebo controlled, multi-center trial (Asthma Trial 4 [NCT00079937]) and an additional supportive study (Asthma Trial 5).

Asthma Trial 4 was a 52-week study that evaluated the safety and efficacy of XOLAIR as add-on therapy in 628 pediatric patients ages 6 to <12 years with moderate to severe asthma inadequately controlled despite the use of inhaled corticosteroids (fluticasone propionate DPI ≥200 mcg/day or equivalent) with or without other controller asthma medications. Eligible patients were those with a diagnosis of asthma >1 year, a positive skin prick test to at least one perennial aeroallergen, and a history of clinical features such as daytime and/or night-time symptoms and exacerbations within the year prior to study entry. During the first 24 weeks of treatment, steroid doses remained constant from baseline. This was followed by a 28-week period during which inhaled corticosteroid adjustment was allowed.

The primary efficacy variable was the rate of asthma exacerbations during the 24-week, fixed steroid treatment phase. An asthma exacerbation was defined as a worsening of asthma symptoms as judged clinically by the investigator, requiring doubling of the baseline inhaled corticosteroid dose for at least 3 days and/or treatment with rescue systemic (oral or IV) corticosteroids for at least 3 days. At 24 weeks, the XOLAIR group had a statistically significantly lower rate of asthma exacerbations (0.45 vs. 0.64) with an estimated rate ratio of 0.69 (95% CI: 0.53, 0.90).

The XOLAIR group also had a lower rate of asthma exacerbations compared to placebo over the full 52-week double-blind treatment period (0.78 vs. 1.36; rate ratio: 0.57; 95% CI: 0.45, 0.72). Other efficacy variables such as nocturnal symptom scores, beta-agonist use, and measures of airflow (FEV1) were not significantly different in XOLAIR-treated patients compared to placebo.

Asthma Trial 5 was a 28-week randomized, double blind, placebo-controlled study that primarily evaluated safety in 334 pediatric patients, 298 of whom were 6 to <12 years of age, with moderate to severe asthma who were well-controlled with inhaled corticosteroids (beclomethasone dipropionate 168-420 mcg/day). A 16-week steroid treatment period was followed by a 12-week steroid dose reduction period. Patients treated with XOLAIR had fewer asthma exacerbations compared to placebo during both the 16-week fixed steroid treatment period (0.18 vs. 0.32; rate ratio: 0.58; 95% CI: 0.35, 0.96) and the 28-week treatment period (0.38 vs. 0.76; rate ratio: 0.50; 95% CI: 0.36, 0.71).

14.2 Chronic Rhinosinusitis with Nasal Polyps

Adult Patients 18 Years of Age and Older

The safety and efficacy of XOLAIR was evaluated in two, randomized, multicenter, double-blind, placebo-controlled clinical trials (CRSwNP Trial 1 [NCT03280550] and CRSwNP Trial 2 [NCT03280537]) that enrolled patients with chronic rhinosinusitis with nasal polyps (CRSwNP) with inadequate response to nasal corticosteroids (CRSwNP Trial 1, n=138; CRSwNP Trial 2, n=127). Patients received XOLAIR or placebo SC every 2 or 4 weeks, with XOLAIR dosage and frequency according to Table 3, for 24 weeks followed by a 4-week follow-up period. All patients received background nasal mometasone therapy during both the treatment period and during a 5-week run-in period. Prior to randomization, patients were required to have evidence of bilateral polyps as determined by a nasal polyp score (NPS) ≥ 5 with NPS ≥ 2 in each nostril, despite use of nasal mometasone during the run-in period. NPS was measured via endoscopy and scored (range 0-4 per nostril: 0= no polyps; 1=small polyps in the middle meatus not reaching below the inferior border of the middle turbinate; 2=polyps reaching below the lower border of the middle turbinate; 3=large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle turbinate; 4=large polyps causing complete obstruction of the inferior nasal cavity) for a total NPS (range 0-8). Patients were furthermore required to have a weekly average of nasal congestion score (NCS) > 1 prior to randomization, despite use of nasal mometasone. Nasal congestion was measured by a daily assessment on a 0 to 3 point severity scale (0=none, 1=mild, 2=moderate, 3=severe). Prior sino-nasal surgery or prior systemic corticosteroid usage were not required for inclusion in the trials and sinus CT scans were not performed to evaluate for sinus opacification. Demographics and baseline characteristics, including allergic comorbidities, are described in Table 14.

Table 14. Demographics and Baseline Characteristics of CRSwNP Trials 1 and 2
Parameter	CRSwNP Trial 1 (n=138)	CRSwNP Trial 2 (n=127)
CRSwNP= chronic rhinosinusitis with nasal polyps; SD=standard deviation; NPS=nasal polyp score; IgE = Immunoglobulin E; IU=international units. For NPS, NCS, sense of smell, post nasal drip, and runny nose, higher scores indicate greater disease severity.
Mean age (years) (SD)	51 (13)	50 (12)
% Male	64	65
Patients with systemic corticosteroid use in the previous year (%)	19	26
Patients with prior surgery for nasal polyps (%)	79 (57)	79 (62)
Mean bilateral endoscopic NPS (SD), range 0-8	6.2 (1.0)	6.3 (0.9)
Mean nasal congestion score (SD) range 0-3	2.4 (0.6)	2.3 (0.7)
Mean sense of smell score (SD) range 0-3	2.7 (0.7)	2.7 (0.7)
Mean post nasal drip score (SD) range 0-3	1.8 (0.9)	1.7 (0.9)
Mean runny nose score (SD) range 0-3	2.0 (0.8)	1.9 (0.9)
Mean blood eosinophils (cells/mcL) (SD)	346 (284)	335 (188)
Mean total IgE IU/mL (SD)	161 (140)	190 (201)
Asthma (%)	54	61
Aspirin exacerbated respiratory disease (%)	20	35

The co-primary endpoints in CRSwNP Trials 1 and 2 were NPS and average daily NCS at Week 24. In both trials, patients who received XOLAIR had a statistically significant greater improvement from baseline at Week 24 in NPS and weekly average NCS, than patients who received placebo. Results from CRSwNP Trials 1 and 2 are shown in Table 15.

The greater improvements in NPS and NCS in the XOLAIR group compared to the placebo group were observed as early as the first assessment at Week 4 in both studies, as seen in Figure 1.

Table 15. Change from Baseline at Week 24 in Nasal Polyp Score and 7-day Average of Daily Nasal Congestion Score in CRSwNP Trials 1 and 2
	Trial 1		Trial 2
	Placebo	XOLAIR	Placebo	XOLAIR
CRSwNP= chronic rhinosinusitis with nasal polyps; LS=least-square. Change from baseline was analyzed using a mixed-effect model of repeated measures (MMRM) model with baseline score, baseline score/timepoint (week) interaction as covariates, and the following factors: geographic region, asthma/aspirin sensitivity comorbidity status, timepoint, treatment group, treatment/timepoint interaction.
Number of patients	65	72	65	62
Nasal Polyp Score
Mean Baseline Score	6.3	6.2	6.1	6.4
LS Mean Change From Baseline at Week 24	0.1	-1.1	-0.3	-0.9
Difference in LS means vs. placebo	-1.1		-0.6
95% CI for difference	-1.6, -0.7		-1.1, -0.1
p-value	<0.0001		0.0140
7-day Average of Daily Nasal Congestion Score
Mean Baseline Score	2.5	2.4	2.3	2.3
LS Mean Change From Baseline at Week 24	-0.4	-0.9	-0.2	-0.7
Difference in LS means vs. placebo	-0.6		-0.5
95% CI for difference	-0.8, -0.3		-0.8, -0.2
p-value	0.0004		0.0017

The mean NPS and NCS at each study week by treatment group is shown in Figure 1.

Figure 1. Mean Change from Baseline in Nasal Congestion Score and Mean Change from Baseline in Nasal Polyp Score by Treatment Group in CRSwNP Trials 1 and 2

XOLAIR had statistically significant improvements on sense of smell score compared to placebo. Sense of smell was measured by a daily assessment on a 0 to 3 point severity scale (0=no symptoms, 1=mild symptoms, 2=moderate symptoms, 3=severe symptoms). The LS mean difference for change from baseline at Week 24 in sense of smell score in XOLAIR compared to placebo was -0.3 (95% CI: -0.6, -0.1) in CRSwNP Trial 1 and -0.5 (95% CI: -0.7, -0.2) in CRSwNP Trial 2.

XOLAIR had statistically significant improvements on post-nasal drip compared to placebo. The LS mean difference for change from baseline at Week 24 in post-nasal drip score in XOLAIR compared to placebo was -0.6 (95% CI: -0.8, -0.3) in CRSwNP Trial 1 and -0.5 (95% CI: -0.8, -0.3) in CRSwNP Trial 2.

XOLAIR had statistically significant improvements on runny nose compared to placebo. The LS mean difference for change from baseline at Week 24 in runny nose score in XOLAIR compared to placebo was -0.4 (95% CI: -0.7, -0.2) in CRSwNP Trial 1 and -0.6 (95% CI: -0.9, -0.4) in CRsWNP Trial 2.

In a pre-specified pooled analysis of systemic corticosteroid use during the 24-week treatment period, there was no significant reduction in systemic corticosteroid use between the treatment arms. The proportion of patients taking systemic corticosteroid in XOLAIR was 2.3% compared to 6.2% in placebo. The odds-ratio of systemic corticosteroid use with XOLAIR compared to placebo was 0.4 (95% CI: 0.1, 1.5).

There were no sino-nasal surgeries reported, in either placebo or XOLAIR arms, in either Trial.

14.3 IgE-Mediated Food Allergy

The safety and efficacy of XOLAIR was evaluated in a multi-center, randomized, double-blind, placebo-controlled Food Allergy (FA) trial [NCT03881696] in 168 adult patients and pediatric patients 1 year of age to less than 56 years who were allergic to peanut and at least two other foods, including milk, egg, wheat, cashew, hazelnut, or walnut (i.e., studied foods). The FA trial enrolled patients who experienced dose-limiting symptoms (e.g., moderate to severe skin, respiratory or gastrointestinal symptoms) to a single dose of ≤100 mg of peanut protein and ≤300 mg protein for each of the other two foods (milk, egg, wheat, cashew, hazelnut, or walnut) during the screening double-blind placebo-controlled food challenge (DBPCFC). Patients with a history of severe anaphylaxis (defined as neurological compromise or requiring intubation) were excluded from the study. Patients were randomized 2:1 to receive a subcutaneous dosage of XOLAIR or placebo based on serum total IgE level (IU/mL), measured before the start of treatment, and by body weight according to Table 4 [see Dosage and Administration (2.4)] for 16 to 20 weeks. After 16 to 20 weeks of treatment, each patient completed a DBPCFC consisting of placebo and each of their 3 studied foods. Following the DBPCFC, the first 60 patients that included 59 pediatric patients and one adult patient who completed the double-blind, placebo-controlled phase of the study could continue to receive XOLAIR in a 24 to 28 week open-label extension.

Efficacy of XOLAIR is based on 165 pediatric patients who were included in the efficacy analyses provided below. The mean age of the pediatric patients was 8 years (age range: 1 to 17 years); 37% were less than 6 years of age, 38% were 6 to less than 12 years of age, and 25% were 12 to less than 18 years of age. Patient population were 56% male, 63% White, 13% Asian, 7% Black, 16% Other, and 55% of patients had a history of asthma.

The primary efficacy endpoint was the percentage of patients who were able to consume a single dose of ≥600 mg of peanut protein without dose-limiting symptoms (e.g., moderate to severe skin, respiratory or gastrointestinal symptoms) during DBPCFC. Table 16 shows XOLAIR treatment led to a statistically higher response rate (68%) than placebo (5%).

The secondary efficacy endpoints were the percentage of patients who were able to consume a single dose of ≥1000 mg of cashew, milk, or egg protein without dose-limiting symptoms during DBPCFC. The study met the secondary endpoints and demonstrated that XOLAIR treatment led to statistically higher response rates than placebo for all three foods. See Table 16 for details.

Table 16. DBPCFC Response Rates in Pediatric Patients for Single Dose of Peanut, Cashew, Milk or Egg Protein in FA Trial
Food, Challenge Dose	Response Rate* (%) (n/N)		Treatment Difference (%) (XOLAIR-Placebo) (95% CI)
Food, Challenge Dose	XOLAIR	Placebo	Treatment Difference (%) (XOLAIR-Placebo) (95% CI)
CI = Confidence interval; DBPCFC = Double-blind placebo-controlled food challenge; n = Number of responders; N = Total number of patients receiving food, challenge dose. Notes: Subjects without an exit DBPCFC or evaluable exit DBPCFC were counted as non-responders; P-values from two-sided Fisher's exact tests were <0.0001 for all the food challenge doses.
* Response defined as consumption of a single dose of the specified amount of food without dose-limiting symptoms. † Consumption of a single dose of ≥1000 mg of peanut protein was an additional secondary endpoint. The key secondary efficacy endpoints were the percentage of patients who were able to consume a single dose of ≥1000 mg of cashew, milk, or egg protein.
Peanut, ≥600 mg	68% (75/110)	5% (3/55)	63% (50%, 73%)
Peanut, ≥1000 mg†	65% (72/110)	0% (0/55)	65% (56%, 74%)
Cashew, ≥1000 mg	42% (27/64)	3% (1/30)	39% (20%, 53%)
Milk, ≥1000 mg	66% (25/38)	11% (2/19)	55% (29%, 73%)
Egg, ≥1000 mg	67% (31/46)	0% (0/19)	67% (49%, 80%)

Seventeen percent of XOLAIR treated patients were not able to consume >100 mg of peanut protein without moderate to severe dose-limiting symptoms. Eighteen, 22, and 41 percent of XOLAIR-treated patients were not able to consume >300 mg of milk, egg, or cashew protein, respectively, without moderate to severe dose-limiting symptoms.

Additional secondary analyses included the percentage of patients who were able to consume at least two or all three foods during DBPCFC. For two foods, 71% of XOLAIR treated patients were able to consume a single dose of ≥600 mg versus 5% in the placebo group and 67% were able to consume a single dose of ≥1000 mg versus 4% in the placebo group. For a single dose of ≥600 mg of three foods, the response rates were 48% in the XOLAIR group versus 4% in the placebo group and for a single dose of ≥1000 mg of three foods, the response rate in the XOLAIR group was 39% while none of the placebo patients were able to consume the challenge dose without symptoms.

The effectiveness of XOLAIR in adults is supported by the adequate and well-controlled trial of XOLAIR in pediatric patients, disease similarity in pediatric and adult patients, and pharmacokinetic (PK) similarity [see Clinical Pharmacology (12.3)].

While efficacy cannot be established from uncontrolled, open-label studies, for 38 pediatric patients who continued XOLAIR for 24-28 weeks in an open-label extension, the percentage of patients who were able to consume ≥600 mg of peanut protein and ≥1000 mg of egg, milk, and/or cashew protein without moderate to severe dose-limiting symptoms was maintained.

14.4 Chronic Spontaneous Urticaria

Adult and Adolescent Patients 12 Years of Age and Older

The safety and efficacy of XOLAIR for the treatment of chronic spontaneous urticaria (CSU), previously referred to as chronic idiopathic urticaria (CIU) was assessed in two placebo-controlled, multiple-dose clinical trials of 24 weeks' duration (CSU Trial 1; n= 319, [NCT01287117]) and 12 weeks' duration (CSU Trial 2; n=322, [NCT01292473]). Patients received XOLAIR 75 mg, 150 mg, or 300 mg or placebo by SC injection every 4 weeks in addition to their baseline level of H1 antihistamine therapy for 24 or 12 weeks, followed by a 16-week washout observation period. A total of 640 patients (165 males, 475 females) were included for the efficacy analyses. Most patients were white (84%) and the median age was 42 years (range 12–72).

Disease severity was measured by a weekly urticaria activity score (UAS7, range 0–42), which is a composite of the weekly itch severity score (range 0–21) and the weekly hive count score (range 0–21). All patients were required to have a UAS7 of ≥16, and a weekly itch severity score of ≥8 for the 7 days prior to randomization, despite having used an H1 antihistamine for at least 2 weeks.

The mean weekly itch severity scores at baseline were fairly balanced across treatment groups and ranged between 13.7 and 14.5 despite use of an H1 antihistamine at an approved dose. The reported median durations of CSU at enrollment across treatment groups were between 2.5 and 3.9 years (with an overall subject-level range of 0.5 to 66.4 years).

In both CSU Trials 1 and 2, patients who received XOLAIR 150 mg or 300 mg had greater decreases from baseline in weekly itch severity scores and weekly hive count scores than placebo at Week 12. Representative results from CSU Trial 1 are shown (Table 17); similar results were observed in CSU Trial 2. The 75-mg dose did not demonstrate consistent evidence of efficacy and is not approved for use.

Table 17. Change from Baseline to Week 12 in Weekly Itch Severity Score and Weekly Hive Count Score in CSU Trial 1*
	XOLAIR 75mg	XOLAIR 150mg	XOLAIR 300mg	Placebo
* Modified intent-to-treat (mITT) population: all patients who were randomized and received at least one dose of study medication. † Score measured on a range of 0–21
N	77	80	81	80
Weekly Itch Severity Score
Mean Baseline Score (SD)	14.5 (3.6)	14.1 (3.8)	14.2 (3.3)	14.4 (3.5)
Mean Change Week 12 (SD)	−6.46 (6.14)	−6.66 (6.28)	−9.40 (5.73)	−3.63 (5.22)
Difference in LS means vs. placebo	−2.96	−2.95	−5.80
95% CI for difference	−4.71, −1.21	−4.72, −1.18	−7.49, −4.10	-
Weekly Hive Count Score †
Mean Baseline Score (SD)	17.2 (4.2)	16.2 (4.6)	17.1 (3.8)	16.7 (4.4)
Mean Change Week 12 (SD)	−7.36 (7.52)	−7.78 (7.08)	−11.35 (7.25)	−4.37 (6.60)
Difference in LS means vs. placebo	−2.75	−3.44	−6.93
95% CI for difference	−4.95, −0.54	−5.57, −1.32	−9.10, −4.76	-

The mean weekly itch severity score at each study week by treatment groups is shown in Figure 2. Representative results from CSU Trial 1 are shown; similar results were observed in CSU Trial 2. The appropriate duration of therapy for CSU with XOLAIR has not been determined.

Figure 2. Mean Weekly Itch Severity Score by Treatment Group Modified Intent to Treat Patients in CSU Trial 1

In CSU Trial 1, a larger proportion of patients treated with XOLAIR 300 mg (36%) reported no itch and no hives (UAS7=0) at Week 12 compared to patients treated with XOLAIR 150 mg (15%), XOLAIR 75 mg (12%), and placebo group (9%). Similar results were observed in CSU Trial 2.