help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Published ahead of print on March 20, 2003, doi:10.1164/rccm.200206-525OC
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
200206-525OCv1
167/12/1655    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kips, J. C.
Right arrow Articles by Pauwels, R. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kips, J. C.
Right arrow Articles by Pauwels, R. A.
American Journal of Respiratory and Critical Care Medicine Vol 167. pp. 1655-1659, (2003)
© 2003 American Thoracic Society

Original Article

Effect of SCH55700, a Humanized Anti-Human Interleukin-5 Antibody, in Severe Persistent Asthma

A Pilot Study

Johan C. Kips, Brian J. O'Connor, Stephen J. Langley, Ashley Woodcock, Huib A. M. Kerstjens, Dirkje S. Postma, Mel Danzig, Francis Cuss and Romain A. Pauwels

Ghent University Hospital, Ghent, Belgium; Guy's, King's, and St Thomas's School of Medicine, London; Medicines Evaluation Unit, North West Lung Centre, Manchester, United Kingdom; University Hospital Groningen, Groningen, The Netherlands; and Schering-Plough Research Institute, Kenilworth, New Jersey

Correspondence and requests for reprints should be addressed to Johan C. Kips, M.D., Ph.D., Department of Respiratory Diseases, Ghent University Hospital, De Pintelaan 185, B 9000 Ghent, Belgium. E-mail: johan.kips{at}rug.ac.be

Antagonizing the effect of interleukin (IL)-5 is a potential new treatment strategy in allergic disorders. We evaluated the safety, biological activity, and pharmacokinetics of SCH55700, a humanized anti-human IL-5 antibody, in subjects with severe persistent asthma treated with oral or high doses of inhaled steroids. In a double-blind, randomized, multicenter trial, a rising single dose of SCH55700 (0.03 mg/kg [n = 2], 0.1 mg/kg [n = 4], 0.3 mg/kg [n = 6], or 1.0 mg/kg [n = 12]) or placebo (n = 8) was administered intravenously. SCH55700 dose dependently reduced circulating eosinophil counts. At a dose of 1.0 mg/kg, the decrease remained significant up to Day 30 [(0.07 ± 0.01) x 109/L versus (0.23 ± 0.04) x 109/L at baseline] (mean ± SEM) (p = 0.05). After administration of SCH55700 at 0.3 and 1.0 mg/kg, a trend toward improvement in baseline FEV1 was observed, which reached significance 24 hours after the 0.3-mg/kg dose (p = 0.019 versus placebo). No significant changes occurred in other clinical indices of disease activity. Adverse events were not different between active treatment and placebo. We conclude that SCH55700 is a biologically active anti-human IL-5 antibody that can be safely used in severe steroid-treated asthma. Its therapeutic potential needs to be addressed in specifically designed efficacy trials.

Key Words: anti-human interleukin-5 antibody • asthma • eosinophil • glucocorticosteroids • interleukin-5




This article has been cited by other articles:


Home page
 Int ImmunolHome page
T. Kouro and K. Takatsu
IL-5- and eosinophil-mediated inflammation: from discovery to therapy
Int. Immunol., October 9, 2009; (2009) dxp102v1.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
N. Mizutani, T. Nabe, and S. Yoshino
Complement C3a Regulates Late Asthmatic Response and Airway Hyperresponsiveness in Mice
J. Immunol., September 15, 2009; 183(6): 4039 - 4046.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
R. F. Lemanske Jr.
Asthma Therapies Revisited: What Have We Learned?
Proceedings of the ATS, May 1, 2009; 6(3): 312 - 315.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
P. Nair, M. M.M. Pizzichini, M. Kjarsgaard, M. D. Inman, A. Efthimiadis, E. Pizzichini, F. E. Hargreave, and P. M. O'Byrne
Mepolizumab for Prednisone-Dependent Asthma with Sputum Eosinophilia
N. Engl. J. Med., March 5, 2009; 360(10): 985 - 993.
[Abstract] [Full Text] [PDF]

Home page
 DMMHome page
A. T. Nials and S. Uddin
Mouse models of allergic asthma: acute and chronic allergen challenge
Dis. Model. Mech., November 1, 2008; 1(4-5): 213 - 220.
[Abstract] [Full Text] [PDF]

Home page
 Rheumatology (Oxford)Home page
K. Polzer, T. Karonitsch, T. Neumann, G. Eger, C. Haberler, A. Soleiman, B. Hellmich, E. Csernok, J. Distler, B. Manger, et al.
Eotaxin-3 is involved in Churg-Strauss syndrome - a serum marker closely correlating with disease activity
Rheumatology, June 1, 2008; 47(6): 804 - 808.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
N. A. Hanania
Targeting Airway Inflammation in Asthma: Current and Future Therapies
Chest, April 1, 2008; 133(4): 989 - 998.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
K. L. Asquith, H. S. Ramshaw, P. M. Hansbro, K. W. Beagley, A. F. Lopez, and P. S. Foster
The IL-3/IL-5/GM-CSF Common Receptor Plays a Pivotal Role in the Regulation of Th2 Immunity and Allergic Airway Inflammation
J. Immunol., January 15, 2008; 180(2): 1199 - 1206.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
E. M. Erin, G. R. Jenkins, O. M. Kon, A. S. Zacharasiewicz, G. C. Nicholson, H. Neighbour, R. C. Tennant, A. J. Tan, B. R. Leaker, A. Bush, et al.
Optimized Dialysis and Protease Inhibition of Sputum Dithiothreitol Supernatants
Am. J. Respir. Crit. Care Med., January 15, 2008; 177(2): 132 - 141.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
P. M. O'Byrne
The Demise of Anti IL-5 for Asthma, or Not
Am. J. Respir. Crit. Care Med., December 1, 2007; 176(11): 1059 - 1060.
[Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
P. Flood-Page, C. Swenson, I. Faiferman, J. Matthews, M. Williams, L. Brannick, D. Robinson, S. Wenzel, W. Busse, T. T. Hansel, et al.
A Study to Evaluate Safety and Efficacy of Mepolizumab in Patients with Moderate Persistent Asthma
Am. J. Respir. Crit. Care Med., December 1, 2007; 176(11): 1062 - 1071.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
M. Larche
Regulatory T Cells in Allergy and Asthma
Chest, September 1, 2007; 132(3): 1007 - 1014.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
Y. Ma, K. T. HayGlass, A. B. Becker, Y. Fan, X. Yang, S. Basu, G. Srinivasan, F. E. R. Simons, A. J. Halayko, and Z. Peng
Novel Recombinant Interleukin-13 Peptide-based Vaccine Reduces Airway Allergic Inflammatory Responses in Mice
Am. J. Respir. Crit. Care Med., September 1, 2007; 176(5): 439 - 445.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
T. Kallinich, K. C. Beier, U. Wahn, P. Stock, and E. Hamelmann
T-cell co-stimulatory molecules: their role in allergic immune reactions
Eur. Respir. J., June 1, 2007; 29(6): 1246 - 1255.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
S. D. Shapiro
Animal Models of Asthma: Pro: Allergic Avoidance of Animal (Model[s]) Is Not an Option
Am. J. Respir. Crit. Care Med., December 1, 2006; 174(11): 1171 - 1173.
[Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
P. C. Fulkerson, C. A. Fischetti, M. L. McBride, L. M. Hassman, S. P. Hogan, and M. E. Rothenberg
A central regulatory role for eosinophils and the eotaxin/CCR3 axis in chronic experimental allergic airway inflammation
PNAS, October 31, 2006; 103(44): 16418 - 16423.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
E. M. Erin, B. R. Leaker, G. C. Nicholson, A. J. Tan, L. M. Green, H. Neighbour, A. S. Zacharasiewicz, J. Turner, E. S. Barnathan, O. M. Kon, et al.
The Effects of a Monoclonal Antibody Directed against Tumor Necrosis Factor-{alpha} in Asthma
Am. J. Respir. Crit. Care Med., October 1, 2006; 174(7): 753 - 762.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
P. M. O'Byrne
Cytokines or their antagonists for the treatment of asthma.
Chest, July 1, 2006; 130(1): 244 - 250.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
L. Pang, M. Nie, L. Corbett, A. Sutcliffe, and A. J. Knox
Mast Cell beta-Tryptase Selectively Cleaves Eotaxin and RANTES and Abrogates Their Eosinophil Chemotactic Activities
J. Immunol., March 15, 2006; 176(6): 3788 - 3795.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
E. Lopez, V. del Pozo, T. Miguel, B. Sastre, C. Seoane, E. Civantos, E. Llanes, M. L. Baeza, P. Palomino, B. Cardaba, et al.
Inhibition of Chronic Airway Inflammation and Remodeling by Galectin-3 Gene Therapy in a Murine Model
J. Immunol., February 1, 2006; 176(3): 1943 - 1950.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. Ozaki, Y.-i. Seki, A. Fukushima, and M. Kubo
The Control of Allergic Conjunctivitis by Suppressor of Cytokine Signaling (SOCS)3 and SOCS5 in a Murine Model
J. Immunol., October 15, 2005; 175(8): 5489 - 5497.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
A. Joetham, K. Takeda, C. Taube, N. Miyahara, A. Kanehiro, A. Dakhama, and E. W. Gelfand
Airway Hyperresponsiveness in the Absence of CD4+ T Cells after Primary but Not Secondary Challenge
Am. J. Respir. Cell Mol. Biol., July 1, 2005; 33(1): 89 - 96.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
A V Kamath, I D Pavord, P R Ruparelia, and E R Chilvers
Is the neutrophil the key effector cell in severe asthma?
Thorax, July 1, 2005; 60(7): 529 - 530.
[Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
R. K. Kumar, C. Herbert, D. C. Webb, L. Li, and P. S. Foster
Effects of Anticytokine Therapy in a Mouse Model of Chronic Asthma
Am. J. Respir. Crit. Care Med., November 15, 2004; 170(10): 1043 - 1048.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
C.A. Ahlstrom-Emanuelsson, L. Greiff, M. Andersson, C.G.A. Persson, and J.S. Erjefalt
Eosinophil degranulation status in allergic rhinitis: observations before and during seasonal allergen exposure
Eur. Respir. J., November 1, 2004; 24(5): 750 - 757.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
R. Djukanovic, S. J. Wilson, M. Kraft, N. N. Jarjour, M. Steel, K. F. Chung, W. Bao, A. Fowler-Taylor, J. Matthews, W. W. Busse, et al.
Effects of Treatment with Anti-immunoglobulin E Antibody Omalizumab on Airway Inflammation in Allergic Asthma
Am. J. Respir. Crit. Care Med., September 15, 2004; 170(6): 583 - 593.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
U. Forssmann, I. Hartung, R. Balder, B. Fuchs, S. E. Escher, N. Spodsberg, Y. Dulkys, M. Walden, A. Heitland, A. Braun, et al.
n-Nonanoyl-CC Chemokine Ligand 14, a Potent CC Chemokine Ligand 14 Analogue That Prevents the Recruitment of Eosinophils in Allergic Airway Inflammation
J. Immunol., September 1, 2004; 173(5): 3456 - 3466.
[Abstract] [Full Text] [PDF]

Home page
 Arch DermatolHome page
M. F. Goldberg
The Skin Is Not the Predominant Problem in Incontinentia Pigmenti
Arch Dermatol, June 1, 2004; 140(6): 748 - 750.
[Full Text] [PDF]

Home page
 BloodHome page
A. D. Klion, M. A. Law, P. Noel, Y.-J. Kim, T. P. Haverty, and T. B. Nutman
Safety and efficacy of the monoclonal anti-interleukin-5 antibody SCH55700 in the treatment of patients with hypereosinophilic syndrome
Blood, April 15, 2004; 103(8): 2939 - 2941.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. Diehl, T. Krahl, L. Rinaldi, R. Norton, C. G. Irvin, and M. Rincon
Inhibition of NFAT Specifically in T Cells Prevents Allergic Pulmonary Inflammation
J. Immunol., March 15, 2004; 172(6): 3597 - 3603.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
M. J. Tobin
Asthma, Airway Biology, and Nasal Disorders in AJRCCM 2003
Am. J. Respir. Crit. Care Med., January 15, 2004; 169(2): 265 - 276.
[Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
A. B. Kay and A. Menzies-Gow
Eosinophils and Interleukin-5: The Debate Continues
Am. J. Respir. Crit. Care Med., June 15, 2003; 167(12): 1586 - 1587.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2003 American Thoracic Society 		  ATS 2008 State of the Art Course