Anti-IL-5 recombinant humanized monoclonal antibody (Mepolizumab) for the treatment of atopic dermatitis

被引:279
作者
Oldhoff, JM
Darsow, U
Werfel, T
Katzer, K
Wulf, A
Laifaoui, J
Hijnen, DJ
Plötz, S
Knol, EF
Kapp, A
Bruijnzeel-Koomen, CAFM
Ring, J
de Bruin-Weller, MS
机构
[1] Univ Utrecht, Med Ctr, Dept Dermatol & Allergol, Utrecht, Netherlands
[2] Tech Univ Munich, Dept Dermatol & Allergy, D-8000 Munich, Germany
[3] GSF TUM, Div Environm Dermatol & Allergy, Munich, Germany
[4] Hannover Med Univ, Dept Dermatol & Allergol, Hannover, Germany
关键词
atopic dermatitis; anti-IL-5; eosinophils; mepolizumab; TARC;
D O I
10.1111/j.1398-9995.2005.00791.x
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background: Eosinophils may play an important role in the pathogenesis of atopic dermatitis (AD). Interleukin-5 is essential for eosinophil growth, differentiation and migration. A monoclonal antibody to human interleukin-5 (mepolizumab) was developed for atopic diseases. This study was designed to study the effect of mepolizumab in AD. Methods: Two single doses of 750 mg mepolizumab, given 1 week apart, were studied in patients with moderate to severe AD using a randomized, placebo-controlled parallel group design. The primary endpoint of 'success' to treatment was defined as the percentage of patients with at least 'marked improvement' after 2 weeks as assessed by the Physician's Global Assessment of Improvement (PGA). Furthermore, SCORing AD (SCORAD), pruritus scoring, number of blood eosinophils and serum thymus and activation-regulated chemokine (TARC) values served as secondary endpoints. Fluticason propionate cream 0.05%, once daily could be used as rescue medication from day 16 if no improvement was recorded. Results: Eighteen patients received mepolizumab and 22 placebo treatment. Peripheral blood eosinophil numbers were significantly reduced in the treatment group compared with placebo (P < 0.05). No clinical success was reached by PGA assessment (P = 0.115), SCORAD (P = 0.293), pruritus scoring and TARC values in the mepolizumab-treated group compared with placebo. However, modest improvement (< 50% improvement) assessed by PGA was scored significantly more in the mepolizumab-treated group compared with placebo (P < 0.05). Conclusion: Two single doses of 750 mg mepolizumab did not result in clinical success in patients with AD, despite a significant decrease in peripheral blood eosinophils.
引用
收藏
页码:693 / 696
页数:4
相关论文
共 17 条
[1]  
[Anonymous], ACTA DERM VENERE S92, DOI [10.2340/00015555924447, DOI 10.2340/00015555924447]
[2]  
Beck LA, 1997, J IMMUNOL, V159, P2962
[3]   Monoclonal anti-interleukin-5 treatment suppresses eosinophil but not T-cell functions [J].
Büttner, C ;
Lun, A ;
Splettstoesser, T ;
Kunkel, G ;
Renz, H .
EUROPEAN RESPIRATORY JOURNAL, 2003, 21 (05) :799-803
[4]   COOPERATION BETWEEN INTERLEUKIN-5 AND THE CHEMOKINE EOTAXIN TO INDUCE EOSINOPHIL ACCUMULATION IN-VIVO [J].
COLLINS, PD ;
MARLEAU, S ;
GRIFFITHSJOHNSON, DA ;
JOSE, PJ ;
WILLIAMS, TJ .
JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 182 (04) :1169-1174
[5]  
ELSNER J, 2002, ACI INT, V14, P151
[6]   Eosinophil's role remains uncertain as anti-interleukin-5 only partially depletes numbers in asthmatic airway [J].
Flood-Page, PT ;
Menzies-Gow, AN ;
Kay, AB ;
Robinson, DS .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2003, 167 (02) :199-204
[7]   Serum thymus and activation-regulated chemokine (TARC) and cutaneous T cell-attracting chemokine (CTACK) levels in allergic diseases: TARC and CTACK are disease-specific markers for atopic dermatitis [J].
Hijnen, DJ ;
de Bruin-Weller, M ;
Oosting, B ;
Lebre, C ;
de Jong, E ;
Bruijnzeel-Koomen, C ;
Knol, E .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2004, 113 (02) :334-340
[8]   Thymus and activation-regulated chemokine in atopic dermatitis: Serum thymus and activation-regulated chemokine level is closely related with disease activity [J].
Kakinuma, T ;
Nakamura, K ;
Wakugawa, M ;
Mitsui, H ;
Tada, Y ;
Saeki, H ;
Torii, H ;
Asahina, A ;
Onai, N ;
Matsushima, K ;
Tamaki, K .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2001, 107 (03) :535-541
[9]   Eosinophils and interleukin-5 - The debate continues [J].
Kay, AB ;
Menzies-Gow, A .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2003, 167 (12) :1586-1587
[10]   Clinical validation and guidelines for the SCORAD index: Consensus report of the European task force on atopic dermatitis [J].
Kunz, B ;
Oranje, AP ;
Labreze, L ;
Stalder, JF ;
Ring, J ;
Taieb, A .
DERMATOLOGY, 1997, 195 (01) :10-19