(omalizumab) 風濕免疫科 林科名醫師

Transcription

1 (omalizumab) 風濕免疫科 林科名醫師

2 生物製劑命名學 生物製劑依其製造機轉而有不同的命名字尾 : 1. cept: 以生物科技將特殊受體與人體 IgG1 之 Fc part 融合者稱之 2. mab: 指單株抗體 (monoclonal antibody) 3. ximab: 指部分結構源自於動物的嵌合式單株 抗體 (chimeric monoclonal antibody ) 4. zumab 或 mumab: 經由生物科技修飾, 以增進與人類抗體相似度之仿人類單株抗體 (humanized monoclonal antibody)

3 Xolair (omalizumab) a monoclonal antibody against immunoglobulin E (IgE) Metabolism: IgE complexes by reticuloendothelial system and endothelial cells in the liver. Bioavailability: 62% Half-life elimination: 26 days (asthma patients); 24 days (chronic idiopathic urticaria patients) Time to peak: 7-8 days Excretion: Primarily via hepatic degradation; intact IgG may be secreted in bile

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5 Indication Asthma according to IgE level and body weight Chronic idiopathic urticaria 150 or 300 mg every 4 weeks

6 Definition and classification of CIU

7 Urticaria is a dermatological disorder characterized by the sudden appearance of itchy hives (wheals), angioedema or both 1 A hive consists of three typical features: 1. Central swellingof variable size, usually surrounded by a reflex erythema 2. Associated itching(pruritus), or sometimes a burning sensation 3. Usually resolves within a few hours and always by 24 hours Hives: Superficial swellings with pale centres surrounded by a red flare Angioedema is typically characterized by: 1. Sudden, pronounced swellingof the lower dermis and subcutis 2. Sometimes pain rather than itching 3. Frequent involvement below mucous membranes 4. Up to 72 hours for resolution The terms itch/pruritus, and hive/wheal are interchangeable. For the purpose of this training tool, itch and hive will be used to describe these key symptoms of urticaria Angioedema of the lips: Pronounced swelling of soft tissue in the mouth 1. Zuberbier T, et al. Allergy 2014;69:868 87

8 Urticaria can be classified based on duration, frequency, and cause 1 Spontaneous Known causes (including autoimmune, infection) Chronic No obvious external specific trigger Unknown causes Urticaria Symptoms daily or almost daily for 6 weeks Acute Symptoms for <6 weeks Inducible Symptoms induced by a specific trigger, e.g. temperature, pressure, cholinergic Chronic idiopathic urticaria Chronic idiopathic urticaria (CIU) can be defined as the spontaneous daily, or almost daily, occurrence of itchy hives, angioedema or both, lasting for 6 weeks or more 1. Adapted from: Zuberbier T, et al. Allergy 2014;69:868 87

9 Epidemiology

10 Urticaria is more common than previously thought 1 CIU affects up to 1% of the population at any given time, accounting for approximately two-thirds of cases of CU 1 3 Female:male ratio is 2:1 1 All age groups can be affected, but peak incidence is between years of age 1 No apparent relationship between urticaria prevalence and education, income, occupation, place of residence or ethnic background 1 Evidence suggests that the prevalence of CU may be increasing 4 8 CU = chronic urticaria CIU = Chronic idiopathic urticaria. 1. Maurer M, et al. Allergy 2011;66:317 30; 2. Kozel MM, et al. Arch Dermatol 1998;134: ; 3. Saini SS. Curr Allergy Asthma Rep 2009;9:286 90; 4. Hellgren L. Acta Allergol. 1972;27:236 40; 5. Gaig P, et al. J Investig Allergol Clin Immunol.2004;14:214 20; 6. Zuberbier T, et al. Clin Exp Dermatol.2010;35:869 73; 7. Zazzali JL, et al. Ann Allergy Asthma Immunol. 2012;108:98 102; 8. Furue M, et al. J Dermatol. 2011;38:

11 CIU is a chronic disease whose duration is estimated to be 1 5 years in most cases 1,2 Of the diagnosed CIU patient population: 50% will resolve within 6 months of onset 2 20% will resolve within 3 years 2 20% will resolve within 5 10 years 2 <2% will resolve within 25 years 2 Years since diagnosis Year 1 Year 2 Year 3 Year 4 Year 5 Year 25 In very rare cases, CIU can persist for up to 50 years 1 CIU = Chronic idiopathic urticaria. 1. Maurer M, et al. Allergy 2011;66:317 30; 2. Adapted from: Beltrani VS. Clin Rev Allergy Immunol 2002;23:

12 Prognostic factors for CIU duration More severe disease 1,2 Studies suggest that although the duration of CIU is generally 1 5 years, it is likely to be longer in patients with: Concurrent angioedema 1,2 Concurrent inducible urticaria 1,3 A positive autologous serum skin test 1,4 CIU = Chronic idiopathic urticaria 1. Maurer M, et al. Allergy 2011;66:317 30; 2. Toubi E, et al. Allergy 2004;59:869 73; 3. Kozel M, et al. J Am Acad Dermatol 2001;45:387 91; 4. Staubach P, et al. Dermatology 2006;212:

13 Diagnosis of CIU

14 Recent revisions to the EAACI/GA 2 LEN/EDF/WAO guidelines have updated the CIU diagnosis steps 1 1. Physical examination of the patient This should include a diagnostic provocation test including drug, food and physical tests only where it is indicated by history 2. Take a thorough history Patients should be questioned regarding: Time-of-onset of disease Frequency/durationof and provoking factors* for hives and/or angioedema *eg. stomach or bowel problems; CSU = Chronic idiopathic urticaria; EAACI = European Academy of Allergy and Clinical Immunology; GA 2 LEN = Global Allergy and Asthma European Network; EDF = European Dermatology Forum; WAO = World Allergy Organization. 1. Zuberbier T, et al. Allergy 2014;69:868 87

15 Current treatments in CIU

16 UAS/ UAS7 蕁麻疹活性 ( 七日 ) 量表 Score 分數 0 None 沒有 1 Mild 輕微 2 Moderate 中度 Wheals 膨疹數量 None 沒有 < 20 wheals/24 hours <20 個 /24 小時內 wheals/24 hours 個 /24 小時內 Itch 搔癢程度 ( 癢的程度 ) None 完全不癢 Mild (present, but not annoying or troublesome) 有點癢感但不造成困擾 Moderate (troublesome, but does not interfere with normal daily activity or sleep) 癢感有造成困擾, 但不影響日常生活或睡眠 3 Intense 嚴重 > 50 wheals/24 hours or large confluent areas of wheals >50 個 /24 小時內或融合成大面積膨疹 Intense (severe itching, which is sufficiently troublesome to interfere with normal daily activity or sleep) 癢感很嚴重, 會影響日常生活或睡眠 計算方式是膨疹分數加上搔癢分數 一日最多 6 分, 七日最多 42 分

17 UAS7 is a measure of CIU severity over 7 days UAS7=28 42: severe CIU 1 typically with an intense itch and >50 hives over 24 hours or large confluent areas of hives UAS7=16 27:* moderate CIU 1 typically with a troublesome itch and up to 50 hives over 24 hours UAS7=7 15:mild CIU 1 typically with a mild itch and fewer than 20 hives over 24 hours 2 UAS7=1 6: ǂ well-controlled CIU; 1 typically with a mild itch and no hives or fewer than 20 hives over 24 hours 2 UAS7=0: ǂ itch-and hive-freeover 7 days 1 *UAS7 16 was an inclusion criterion for Phase III clinical trials of omalizumab in patients with refractory CIU; ǂ UAS7 6 (well controlled disease) and UAS7=0 (complete response) were key secondary endpoints in these trials; UAS7 = weekly Urticaria Activity Score. 1. Stull D, et al. EAACI 2014; 2. Zuberbier T, et al. Allergy 2014;69:

18 EAACI/GA 2 LEN/EDF/WAO guidelines 1 Treatment algorithm for urticaria according to the 2013 First line Second generation H 1 -antihistamines Second line If symptoms persist after 2 weeks Second generation H 1 -antihistamines at up to 4-fold increased dose Third line If symptoms persist after 1 4 further weeks Add on to second line:* Omalizumab, cyclosporin A or montelukast Exacerbations: short course (maximum 10 days) of corticosteroids A number of additional treatment options are mentioned in the EAACI/GA 2 LEN/EDF/WAO guidelines, but are not included in the recommended treatment algorithm due to limited supporting evidence; *the order of third-line treatments does not reflect preference; Licensed in Europe and the US; Not licensed for treatment in CIU.. EAACI = European Academy of Allergy and Clinical Immunology; GA 2 LEN = Global Allergy and Asthma European Network; EDF = European Dermatology Forum; WAO = World Allergy Organization. 1. Zuberbier T, et al. Allergy 2014;69:

19 2014 TDA Recommended CU Treatment Flow 1 st line Second-generation H1-antihistamine If symptoms persist after 1-2 weeks 2 nd line * If symptoms persist after 1-2 further weeks, Change to another 2 nd line Combination of the above 2 nd line Exacerbation: systemic steroid (maximum 10 days within 1 month) If symptoms persist after 4-6 further weeks 3 rd line H1 antihistamine and omalizumab are the licensed treatments available for CIU (FDA/EMA)

20 Other anti-inflammatory agents Alternative treatment EAACI evidence EAACI recommend BSACI grade MTX Very low Weak D (rare) BSACI Specific indication/comments/side effects Beneficial for corticosteroid-dependent chronic idiopathic urticaria (two patients). Efficacy in urticarial vasculitis (one patient) HCQ Very low Weak -- Improvement of QoL, but no reduction in urticaria scores or medication requirements Dapsone Very low Weak D (rare) Colchicine Ineffective -- D (rare) AZA Less evidence available Ketotifen Low Weak Several single case reports of successful treatments of urticarial vasculitis in resistant cases. Helped one patient with autoimmune thyroiditis to stop oral steroid treatment One patient showed total clearance of urticarial vasculitic rashes and chronic vasculitic ulceration previously unresponsive to steroids in combination with dapsone and HCQ 20 08Jun2014 TDA Urticaria Consensus

21 Conclusions CIU 的治療目標是能快速並完全控制症狀 1 CIU 的處置, 依據 2013 年更新並於 2014 年公布的國際 EAACI/ GA 2 LEN/ EDF/ WAO 指南 2,3, 建議 : 使用核准劑量的第二代 H1- 抗組織胺作為第一線治療 3 將第二代 H1- 抗組織胺的劑量提高到核准劑量的四倍作為第二線治療 3 針對難治型 CSU 的高劑量 H1- 抗組織胺療法, 可在現行療法額外添加 omalizumab 環孢黴素或 montelukast 3, 作為第三線治療 成人或青少年 (12 歲以上 )CSU/ CIU 患者, 對於 H1- 抗組織胺治療反應不佳 4,5, 仍有症狀者, 歐盟 / 美國核准改用 300 毫克的 omalizumab Montelukast 使用在蕁麻疹中, 相關療效的證據不足 3 1. Maurer M, et al. Allergy 2011;66:317 30; 2. Zuberbier T, et al. Allergy 2009;64: ; 3. Zuberbier T, et al. Allergy 2014;69:868 87; 4. Xolair SmPC 2014; 5. Xolair PI 2014.

22 Omalizumab in the Management of Chronic idiopathic urticaria

23 MYSTIQUE Omalizumab in H 1 -antihistaminerefractory CSU: Placebo-controlled, Dose-ranging Phase II Study Authors: Sarbjit Saini, MD; Marcus Maurer, MD; Allen Kaplan, MD; Sheldon Spector MD; Karin E. Rosén, MD, PhD; Hsin-Ju Hsieh, PhD; Edward Conner, MD; Dennis A. Wong, MD Saini S, et al. J Allergy Clin Immunol. 2011;128:567 73

24 Study Design Phase II Phase II, dose-ranging, prospective, multicentre, randomized (1:1:1:1), double-blind, placebo-controlled, parallel-group study Randomization Treatment period End of study OMA 600 mg (n=21) Screening Run-in OMA 300 mg (n=25) OMA 75 mg (n=23) 12-week follow-up period Placebo (n=21) Weeks Single dose OMA, omalizumab Saini S, et al. J Allergy Clin Immunol. 2011;128:567 73

25 Mean Change From Baseline to Week 4 in UAS7 Scores: Primary Efficacy Outcome Placebo OMA 75 mg OMA 300 mg OMA 600 mg Mean (SD) change in UAS7 scores p= p< p=0.047 OMA, omalizumab Saini S, et al. J Allergy Clin Immunol. 2011;128:567 73

26 Omalizumab Demonstrates Efficacy In CIU With Once Monthly Dosing Peak response at 4 weeks post-dose with gradual return to symptoms approximately 8 weeks post-dose suggesting monthly as a suitable frequency for omalizumab administration. Saini S, et al. J Allergy Clin Immunol. 2011;128:567 73

27 Safety Outcomes Phase II 44% and 40.7% of patients experienced at least 1 AE during the treatment and follow-up periods, respectively Majority of AEs were mild to moderate in severity and considered not related to study drug No serious AEs, clinically relevant laboratory findings, or deaths were reported during the treatment period One serious AE, chest pain in a patient with a prior history of chest pain was observed during the 12-week follow-up period (day 101) Diagnosed as atypical chest pain, likely musculoskeletal, OMA 300 mg group AE, adverse event; OMA, omalizumab Saini S, et al. J Allergy Clin Immunol. 2011;128:567 73

28 Phase III randomized, double-blind, placebo-controlled studies evaluating efficacy and safety of omalizumab in refractory Chronic idiopathic urticaria Authors: Maurer M, et al. N Engl J Med. 2013; 368: Kaplan A, et al. J Allergy Clin Immunol. 2013; 132:101-9 Saini SS, et al. J Invest Dermatol. 2014

29 ASTERIA I, ASTERIA II, GLACIAL Study Design Patients (12 75 years) with CIU refractory to standard of care ASTERIA I 24 week treatment 75 mg/150 mg/300 mg /Placebo 16 week follow-up ASTERIA II 12 week treatment 75 mg/150 mg/300 mg/placebo 16 week follow-up = monthly flat dosing = primary endpoint (Week 12) GLACIAL 24 week treatment 300 mg/placebo 16 week follow-up week screening period Background therapy throughout treatment period Presence of itch/hives prior to enrolment UAS7 Weekly itch score ASTERIA I (Q4881g) H 1 -antihistamines (approved doses) ASTERIA II (Q4882g) H 1 -antihistamines (approved doses) GLACIAL (Q4883g) H 1 -antihistamines up to 4x approved dose plus H 2 -blocker / LTRA 8 Weeks 8 Weeks >6 weeks 16 for at least 4 out of the 7 days in the week prior to randomization 8 for the 7 days prior to randomization Patients must have been on background therapy for at least 3consecutive days immediately prior to Day-14 screening visit

30 Primary and Secondary Endpoints Primary Endpoint Secondary Endpoints ASTERIA I ASTERIA II GLACIAL Change from baseline to Week 12 in weekly itch severity score (ISS) At Week 12: Change from baseline in UAS7 Change from baseline in weekly # of hives score Time to MID ( 5 points) response in weekly ISS Proportion of patients with UAS7 6 Proportion of weekly ISS MID responders Change from baseline in weekly size of largest hive score Change from baseline in DLQI Proportion of angioedema-free days from Week4 to Week12 of therapy Proportion of Complete Responders (UAS7=0)* Safety Same as ASTERIA I and ASTERIA II *Exploratory endpoint in ASTERIA II. Maurer M, et al. N Engl J Med. 2013; 368: Kaplan A, et al. J Allergy Clin Immunol. 2013; 132:101-9 Saini SS, et al. J Invest Dermatol [Epub ahead of print]

31 Baseline Demographics: Balanced across the Phase III studies ASTERIA I N=318 ASTERIA II N=322 GLACIAL N=335 Age (yr) Mean (SD) 41.2 (14.5) 42.5 (13.7) 43.1 (14.1) Age group (yr) Sex Race (5.7%) 10 (3.1%) 11 (3.3%) (43.1%) 135 (41.9%) 125 (37.3%) (46.5%) 159 (49.4%) 178 (53.1%) (4.7%) 18 (5.6%) 21 (6.3%) Female 231 (72.6%) 244 (75.8%) 241 (71.9%) Asian 14 (4.4%) 9 (2.8%) 9 (2.7%) Black 33 (10.4%) 28 (8.7%) 21 (6.3%) White 263 (82.7%) 272 (84.5%) 298 (89.0%) Weight (kg) Mean (SD) 82.2 (21.0) 82.4 (21.9) 83.9 (22.5) < 80 kg 158 (49.7%) 166 (51.6%) 168 (50.1%) BMI, Mean (SD) 29.3 (6.8) 29.8 (7.3) 29.8 (7.8)

32 Duration of CIU (years) Disease Characteristics: Balanced across the Phase III studies ASTERIA I N=318 ASTERIA II N=322 GLACIAL N=335 Mean (SD) 6.9 (9.1) 6.5 (8.6) 7.4 (9.5) Median Number of Previous CIU Medications, Mean (SD) 4.7 (2.8) 4.3 (2.7) 6.0 (2.6) In-Clinic UAS, Mean (SD) 5.3 (0.8) 5.3 (0.7) 5.2 (0.8) UAS7, Mean (SD) 31.1 (6.6) 30.7 (6.8) 30.9 (6.6) Weekly Itch Severity Score, Mean (SD) 14.3 (3.5) 14.0 (3.7) 14.0 (3.6) Weekly Number of Hives Score, Mean (SD) 16.8 (4.3) 16.7 (4.3) 16.9 (4.3) Presence of angioedema * 151 (47.5%) 131 (40.7%) 178 (53.1%) Presence of anti-fcɛri autoantibody (CU index test) Total IgE level (IU/mL) 80 (25.2%) 94 (29.3%) 103 (30.9%) Mean (SD) (387.8) (231.9) (287.7) Median *7 days prior to randomization Maurer M, et al. N Engl J Med. 2013; 368: Kaplan A, et al. J Allergy Clin Immunol. 2013; 132:101-9 Saini SS, et al. J Invest Dermatol [Epub ahead of print]

33 Mean Itch-Severity Score* by Week Time course and dose response in ASTERIA II and GLACIAL Fast onset of treatment effect Dose-response relationship Efficacy maintained over treatment period (12 and 24 weeks) Return of CIU symptoms was similar for 12 vs. 24 weeks of treatment. No evidence of rebound Placebo Omalizumab 75 mg Omalizumab 150 mg Omalizumab 300 mg = monthly flat dosing Mean weekly itch severity score Mean weekly itch severity score (BOCF) at visit by treatment group Modified intention to treat patients *Missing weekly score imputed by baseline; BOCF, baseline observation carried forward ASTERIA II background medication was H 1 -antihistamines (approved doses); GLACIAL background medication was H 1 - antihistamines (up to four times the approved dose) plus H 2 -antihistamines and/or LTRAs.

34 Responder Analysis: UAS7 6 at Week Percentage patients achieving UAS Statistically significant treatment effects for the 150 mg and 300 mg dose * p<0.05. PBO, placebo. ASTERIA II background medication was H 1 -antihistamines (approved doses); GLACIAL background medication was H 1 - antihistamines (up to four times the approved dose) plus H 2 -antihistamines and/or LTRAs.

35 Percentage patients achieving UAS7=0 Complete Responders: UAS7=0 at Week 12 Statistically significant treatment effect for 300 mg dose across all studies * p<0.05. PBO, placebo. ASTERIA II background medication was H 1 -antihistamines (approved doses); GLACIAL background medication was H 1 - antihistamines (up to four times the approved dose) plus H 2 -antihistamines and/or LTRAs.

36 Incidence of Adverse Events During Each Study No major imbalances between treatment groups ASTERIA I* ASTERIA II** GLACIAL* Placebo 75 mg 150 mg 300 mg Placebo 75 mg 150 mg 300 mg Placebo 300 mg Number of patients Any AE 53 (66.3%) 55 (78.6%) 72 (82.8%) 57 (70.4%) 48 (60.8%) 45 (59.2%) 59 (67.0%) 52 (65.8%) 65 (78.3%) 211 (83.7%) Serious AE 5 (6.3%) 2 (2.9%) 5 (5.7%) 2 (2.5%) 2 (2.5%) 1 (1.3%) 1 (1.1%) 5 (6.3%) 5 (6.0%) 18 (7.1%) AE leading to treatment withdrawal 7 (8.8%) 2 (2.9%) 4 (4.6%) 2 (2.5%) -- 3 (3.9%) 2 (2.3%) -- 6 (7.2%) 12 (4.8%) AE suspected to be caused by study drug 4 (5.0%) 6 (8.6%) 9 (10.3%) 14 (17.3%) 3 (3.8%) 7 (9.2%) 8 (9.1%) 7 (8.9%) 11 (13.3%) 28 (11.1%) Severe AE 8 (10.0%) 7 (10.0%) 8 (9.2%) 13 (16.0%) 7 (8.9%) 4 (5.3%) 5 (5.7%) 6 (7.6%) 13 (15.7%) 42 (16.7%) AE, adverse events *Study duration = 40 weeks; **Study duration = 28 weeks.

37 AEs of Frequency 3% (Treatment Period) Most frequently reported AEs were headache and nasopharyngitis ASTERIA I* ASTERIA II** GLACIAL* Placebo 75 mg 150 mg 300 mg Placebo 75 mg 150 mg 300 mg Placebo 300 mg Number of patients Any AE 41 (51.3%) 41 (58.6%) 60 (69.0%) 46 (56.8%) 32 (40.5%) 32 (42.1%) 42 (47.7%) 35 (44.3%) 53 (63.9%) 164 (65.1%) Diarrhoea (3.8%) 1 (1.3%) 2 (2.3%) 2 (2.5%) 5 (6.0%) 9 (3.6%) Nausea (6.0%) 10 (4.0%) Nasopharyngitis 10 (12.5%) 3 (4.3%) 11 (12.6%) 9 (11.1%) 4 (5.1%) 8 (10.5%) 5 (5.7%) 7 (8.9%) 7 (8.4%) 22 (8.7%) Sinusitis 4 (5.0%) 5 (7.1%) 4 (4.6%) 3 (3.7%) 1 (1.3%) 2 (2.6%) -- 3 (3.8%) 5 (6.0%) 19 (7.5%) Upper respiratory tract infection 3 (3.8%) 3 (4.3%) 3 (3.4%) 1 (1.2%) 4 (5.1%) (5.1%) 2 (2.4%) Bronchitis 5 (6.3%) 4 (5.7%) 2 (2.3%) 1 (1.2%) 2 (2.5%) 2 (2.6%) -- 3 (3.8%) Arthralgia -- 1 (1.4%) 5 (5.7%) 3 (3.7%) 1 (1.3%) 1 (1.3%) 1 (1.1%) 3 (3.8%) Headache 2 (2.5%) 4 (5.7%) 8 (9.2%) 5 (6.2%) 5 (6.3%) 1 (1.3%) 14 (15.9%) 6 (7.6%) 3 (3.6%) 18 (7.1%) 22 (8.7%) Migraine (3.4%) (3.6%) 4 (1.6%) Cough 2 (2.5%) 3 (4.3%) 2 (2.3%) (3.6%) 10 (4.0%) Idiopathic urticaria 2 (2.5%) 5 (7.1%) 1 (1.1%) 1 (1.2%) 1 (1.3%) 3 (3.9%) -- 1 (1.3%) 6 (7.2%) 7 (2.8%) Urticaria 6 (7.5%) 5 (7.1%) 4 (4.6%) 2 (2.5%) 1 (1.3%) 4 (5.3%) 1 (1.1%) 1 (1.3%) 7 (8.4%) 12 (4.8%) AE, adverse events *Treatment period = 24 weeks; **Treatment period = 12 weeks.

38 AE of Xolair in CIU >10%: Central nervous system: Headache (6% to 12%) 1% to 10%: Cardiovascular: Peripheral edema ( 2%) Central nervous system: Anxiety ( 2%), migraine ( 2%) Dermatologic: Alopecia ( 2%) Gastrointestinal: Toothache ( 2%) Genitourinary: Urinary tract infection ( 2%) Infection: Fungal infection ( 2%) Local: Injection site reaction (3%) Neuromuscular & skeletal: Arthralgia (3%), limb pain ( 2%), musculoskeletal pain ( 2%), myalgia ( 2%) Respiratory: Nasopharyngitis (9%), sinusitis (5%), upper respiratory tract infection (3%), asthma ( 2%), oropharyngeal pain ( 2%), sinus headache ( 2%), cough (2%), viral upper respiratory tract infection ( 2%) Miscellaneous: Fever ( 2%) uptodate

39 Conclusions Omalizumab 150 mg and 300 mg demonstrated a statisticallysignificant treatment effect in the weekly ISS. No new safety signals were identified compared to the known safety profile of omalizumab in allergic asthma.

40 Xolair (omalizumab) 採用簡單的給藥計畫 Xolair (omalizumab) 為凍晶粉末, 以水調配後經皮下注射給藥 * 4 核准劑量為每四週 300 mg (150 mg 兩劑 ) / 或是每四週 150 mg - 建議醫師應定時評估是否繼續患者的療程 -CIU 患者連續用藥超過 6 個月以上的長期臨床試驗經驗目前仍不足 患者施打 Xolair (omalizumab) 過後應留院觀察

41 FDA The FDA has reviewed safety studies that suggest a slightly increased risk of serious cardiovascular and cerebrovascular adverse events in patients being treated with Xolair (omalizumab). The review found no difference in the rates of cancer between patients treated with Xolair and those not treated with Xolair, but a potential cancer risk cannot be ruled out due to study limitations.