The Clinical Experience of Omalizumab Treatment In Patients with Refractory Chronic Urticaria Young-Hee Nam, 1 Joo-Hee Kim, 2 Hyun Jung Jin, 3 Eui-Kyung Hwang, 4 Yoo-Seob Shin, 4 Young-Min Ye, 4 Hae-Sim Park 4* 1 Department of Internal Medicine, Dong-A University School of Medicine 2 Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine 3 Department of Internal medicine, Yeungnam University College of Medicine 4 Department of Allergy and Clinical Immunology, Ajou University School of Medicine
Background Chronic urticaria (CU) is a skin disorder characterized by the spontaneous occurrence of widespread, transient wheals and pruritus, often accompanied by angioedema, persisting for 6 weeks. Zuberbier T et al. Allergy 2009;64:1417-26 DuBuske L et al. Am J Clin Dermatol 2007;8:271-83 Approximately 30% to 50% of patients with CIU reportedly produce IgG autoantibodies against either IgE or its highaffinity receptor (FceRI). Sabroe RA et al. J Allergy Clin Immunol 2002;110:492-9 Omalizumab, a recombinant humanized mab that selectively binds to IgE, inhibits the binding of IgE to the highaffinity IgE receptor (FceRI) on the surface of mast cells and basophils and reduces the number of FceRI receptors on basophils in atopic patients. Beck LA et al. J Allergy Clin Immunol 2005;1050:73-88
Several studies showed omalizumab is an effective for CU resistant to antihistamines. Kaplan AP et al. J Allergy Clin Immunol 2008;122:569-73 Saini S et al. J Allergy Clin Immunol 2011;128:567-73 Maurer M et al. J Allergy Clin Immunol 2011;128:202-9 Ferrer M et al. J Allergy Clin Immunol 2011;127:1300-2 Metz M et al. Allergy 2008;63:247-9 Spector SL et al. Ann Allergy Asthma Immunol 2007 Aug;99(2):190-3. However, there has been no report about efficacy and safety of omalizumab treatment in CU in Korean population.
Objective We investigated the efficacy of omalizumab in patients with CU symptomatic despite antihistamine therapy.
Subjects & Methods We conducted a retrospective study of patients who were treated with omalizumab for CU. Patients with refractory CU were defined as having symptoms for at least 6 weeks with persistent hives, and not controlled most days of the week, despite the use of a fourth-line therapy for more than 4 weeks, according to EAACI/GALEN guidelines. Omalizumab was administered every 2 or 4 weeks for 24 weeks, dosed according to the patient s body weight, and serum IgE levels. Urticaria activity score (UAS) and chronic urticaria-specific QOL (CU-QOL) questionnaires were completed every 4 weeks.
Treatment algorithm for CU Zuberbier T et al. Allergy 2009: 64: 1427 1443
Responses to omalizumab - Remission: no symptoms and no requirement for medications at least 4 weeks - Responsive: stepping down more than one level of therapy compared with baseline - Refractory: neither remission nor any symptom improvement during the treatment period
Urticaria Activity Score Parameters Score Wheal numbers None 0 Wheal distribution (% of BSA) 1 20 1 21 50 2 >50 3 None 0 <25% 1 25 50% 2 >50% 3 Wheal duration None 0 <4h 1 4 12h 2 >12h 3 Wheal size (diameter) None 0 <1cm 1 1 3cm 2 >3 cm 3 Pruritus None 0 Mild 1 Moderate 2 Severe 3 Ye et al. Clin Exp Dermatol 2012 in press
CU-QOL Lee et al. Korean J Asthma Allergy Clin Immunol 2010;30 Suppl 2:S384 문항질문 1 두드러기부위가가렵다 2 두드러기부위가부어불편하다 3 두드러기부위가화끈거리고열감이있어불편하다 4 밤에가려워서잠을설치게된다 5 두드러기로우울하다 6 두드러기로짜증이난다 7 두드러기로인해내모습이창피하다 8 두드러기로일상생활의만사가귀찮고의욕이없다 9 두드러기로인해내삶에대한자싞감이떨어진다 그렇지않았다 : 0 조금그랬다 : 1 보통이었다 : 2 꽤그랬다 : 3 많이그랬다 : 4 10 두드러기를일으킬지몰라새로운것 ( 음식이나환경등 ) 에노출되는것이두렵다 11 다른사람들과함께음식을먹어야하는상황에서눈치가보인다 12 두드러기를일으키는음식을가려먹어야하는것이힘들다 13 두드러기에대해다른사람들이놀려서스트레스를받는다 14 다른사람들이내두드러기에대해이야기하는것같아불편하다 15 두드러기로사람만나는것이꺼려진다 16 두드러기로내품위가떨어진것같은생각이든다 17 두드러기로인해다른사람에대해열등감을느낀다
Results
Table 1. Clinical characteristics of the subjects Clinical characteristics n=26 (%) Age * (y), (range) 43.1 ± 8.4 (28-58) Male sex (%) 14 (53.8) Duration of disease * (month), (range) 63 ± 72.7 (3-312) History of underlying disease 7 (26.9) History of allergic disease 22 (84.6) Atopy 17 (68) Angioedema 13 (50) Physical urticaria 13 (50) Atopic dermatitis 14 (53.8) NSAID hypersensitvity 16 (61.5) Family history of allergic disease 8 (30.8) Mean basal UAS * (n=18) (range) 12.11±1.97 (8-15) Mean basal QOL * (n=17) (range) 33.35±13.58 (11-60) Total IgE* (KU/ml) (range) 247.7 ± 274.6 (23-1205) Log total IgE* (KU/ml) (range) 2.18 ± 0.45 (1.36-3.08) ANA 5 (19.2) Anti-thyroglobulin antibody 6 (23.1) Anti-microsomal antibody 1 (7.7) NSAID, nonsteroidal antiinflammatory drug; UAS, urticaria activity score; QOL, quality of life; ANA, antinuclear antibody * Data presented as mean ± SD
Score (mean + SD) 80 UAS CU-QOL P = 0.001 P = 0.004 70 60 50 40 30 20 10 P = 0.001 P = 0.001 0 0 12 24 Anti-IgE antibody treatment (weeks) Figure 1. Changes in urticaria activity score (UAS) and chronic urticaria-specific quality of life (CU-QOL) scores during anti-ige antibody (omalizumab) treatment
Mean ± SD (equivalent dose of loratadine 10 mg/day, mg/week) 300 200 P = 0.001 100 0 0 4 8 12 16 20 24 (weeks) -100 Figure 2. Change in H1-antihistamine requirement during anti-ige antibody treatment
Table 2. Comparison of clinical parameters between remitted and non-remitted groups at week 24 Clinical parameters Group I (n=14) Group II (n=12) P value Age * (y) 43.86±7.33 42.17±9.71 0.595 Male sex (%) 7 (50) 7 (58.3) 0.713 Duration of disease * (month) 78.93±91.84 44.42±36.82 0.494 History of allergic diseases 14 (100) 8 (66.7) 0.033 Atopy 9 (69.2) 8 (66.7) > 0.9 Angioedema 6 (42.9) 7 (58.3) 0.695 Physical urticaria 8 (57.1) 5 (41.7) 0.695 NSAID hypersensitivity 6 (42.9) 10 (83.3) 0.051 Family history of allergic diseases 8 (57.1) 0 0.002 Baseline UAS * (range) 12.78±1.72 11.44±2.07 (8-15) 0.161 Baseline CU-QOL score * (range) 29.1129.11±11.84 40.88±13.32 0.074 Log serum total IgE* (KU/ml) 2.26±0.49 (1.36-2.91) 2.08±0.41 (1.4-3.08) 0.322 NSAID, nonsteroidal anti-inflammatory drug; UAS, urticaria activity score; CU-QOL, chronic urticaria-specific quality of life. * Data are presented as mean ± SD. Subjects who achieved remission at week 24. Subjects who could not achieve remission at week 24.
Recurred, and maintained baseline therapy (n = 5, 19.2%) Remitted group (n = 22, 84.6%) Recurred, but achieved step-down therapy (n = 3, 11.6%) Total enrolled subjects (n = 26) Maintain remission (n = 14, 53.8%) Responsive group (n = 19, 73.1%) Step-down therapy (n = 2, 7.7%) Non-remitted group (n = 4, 15.4%) Refractory state (n = 2, 7.7%) Figure.3. Clinical courses of the subjects
Conclusion Omalizumab is an effective and safe treatment for patients with refractory CU. The findings suggest that a personal or family history of allergic diseases may be a favorable factor for predicting remission. Further studies will be needed to investigate potential factors for differentiating favorable and unfavorable responders.
Question & Discussion