Randomised, dose-ranging, placebo-controlled study of chimeric antibody to CD4 (keliximab) in chronic severe asthma

  title={Randomised, dose-ranging, placebo-controlled study of chimeric antibody to CD4 (keliximab) in chronic severe asthma},
  author={Onn Min Kon and B. S. Sihra and Chris Compton and Thomas Brent Leonard and A. Barry Kay and Neil C Barnes},
  journal={The Lancet},
The Effects of a Monoclonal Antibody Directed against Tumor Necrosis Factor-α in Asthma
Rationale: Neutralization of tumor necrosis factor-α (TNF-α) is an effective antiinflammatory therapy for several chronic inflammatory diseases.Methods and Objectives: We undertook a double-blind,
The effects of an anti-CD4 monoclonal antibody, keliximab, on peripheral blood CD4+ T-cells in asthma.
Keliximab, as an anti-CD4 monoclonal antibody, leads to a transient reduction in the number ofCD4+ T-cells and modulation of CD4+ receptor expression in severe asthmatics, in addition to a reduction in allergen-induced proliferation.
Anti-T cell strategies in asthma
Controlled clinical trials of cyclosporin A were effective in both chronic asthma and in a model of provoked asthma, and strategies targeting T cell co-stimulatory molecules and T-cell derived cytokines may be of therapeutic utility.
Evaluation of new drugs for asthma and COPD: Endpoints, biomarkers and clinical trial designs
Clinical trial designs range from studies on lung function, symptoms and exercise performance, inflammatory biomarkers, natural history of chronic stable disease, prevention and treatment of exacerbations, and effects on cachexia and muscle function to ex vivo whole blood stimulation to enable pharmacokinetic/pharmacodynamic modelling in establishing an optimal dosage regimen relatively early in human clinical studies.
The role of monoclonal antibodies in the treatment of severe asthma
An overview of present and future monoclonal antibody therapies for the treatment of patients with severe asthma is provided.
What is new in the management of childhood asthma?
It is evident that the current ICS are already very efficient and safe, it will be difficult to introduce further improved formulations, so the most fruitful effort shall be in developing patient friendly easy to use targeted delivery systems.
Biologic therapy for atopic asthma and beyond
The authors will review the existing efficacy and safety data from clinical trials of some of the new biologic therapies that are in development for severe asthma.
Asthma Refractory to Glucocorticoids
  • C. Corrigan
  • Medicine, Biology
    American journal of respiratory medicine : drugs, devices, and other interventions
  • 2002
Meta-analysis of trials of methotrexate in oral glucocorticoid-dependent asthma have confirmed that concomitant weekly metotrexate for a minimum of 3 to 6 months enables significant (approximately 20%) overall reduction in oral glucose requirements, although only approximately 60% of patients show a significant response.
Alternative strategies in the treatment of bronchial asthma
  • In ‘T Veen, Sterk, Bel
  • Medicine
    Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
  • 2000
Bronchial asthma is a common disease, of which most patients are adequately treated by standard therapy [1]. However, a small but worrying group of patients with asthma has severe, unremitting
What's in the pipeline? Prospects for monoclonal antibodies (mAbs) as therapies for lung diseases.
The scientific rationale for generating mAb therapies directed specifically toward COPD and asthma is discussed and it is believed that as a therapeutic class, mAbs offer the opportunity to alter symptoms, progression and outcome of chronic pulmonary diseases.


Double-blind, placebo-controlled study of cyclosporin A as a corticosteroid-sparing agent in corticosteroid-dependent asthma.
Predictable changes in renal function and blood pressure, and an increased incidence of hypertrichosis and paresthesia were observed in the patients treated with CsA, but these did not necessitate withdrawal from the study, and were reversed during a 4-wk run-out period.
Treatment of refractory rheumatoid arthritis with a chimeric anti-CD4 monoclonal antibody. Long-term followup of CD4+ T cell counts.
The prolonged decrease in CD4+ T cell numbers suggests that the capacity to reconstitute CD4- T cells in this patient population (treated with methotrexate) is limited.
CD4 T-lymphocyte activation in acute severe asthma. Relationship to disease severity and atopic status.
The serum concentrations of interferon-gamma and soluble IL-2R were significantly elevated in patients with acute severe asthma as compared with all the control groups and decreased as the patients improved clinically during the first 3-day period of hospital treatment.
CD4 antibody therapy in systemic lupus erythematosus.
CD4 monoclonal antibodies are effective in animal models for systemic lupus erythematosus, diabetes mellitus, rheumatoid arthritis, myasthenia gravis, and multiple sclerosis.
Identification of activated T lymphocytes and eosinophils in bronchial biopsies in stable atopic asthma.
Examination of mucosal biopsies obtained from both central and subsegmental bronchi showed that the highest number of CD45-, DC3-, DC4-, and CD8-positive cells were found in the group with asthma, and there was a significant increase in the number of interleukin-2 receptor (CD25)-positive cells.
General aspects of cytokine-release syndrome: timing and incidence of symptoms.
The potential for use of nonactivating anti-CD3 antibodies may obviate the symptom complex entirely and strategies to moderate CRS show promise.
Eosinophilic inflammation in asthma.
Eosinophilic inflammation of the airways is correlated with the severity of asthma and these cells are likely to play a part in the epithelial damage seen in this disease.