Biologics and the treatment of chronic rhinosinusitis

Abstract

The study by Gevaert et al1Gevaert P. Calus L. Van Zele T. Blomme K. De Ruyck N. Bauters W. et al.Omalizumab is effective in allergic and non-allergic patients with nasal polyps and asthma.J Allergy Clin Immunol. 2013; 131: 110-116Abstract Full Text Full Text PDF PubMed Scopus (480) Google Scholar reports positive results for a randomized, double-blind, placebo-controlled phase II trial using omalizumab for the management of allergic and nonallergic patients with nasal polyps and asthma. The primary end point was reduction in the nasal polyp score, and in contrast to an earlier, underpowered negative trial with omalizumab,2Pinto J.M. Mehta N. DiTineo M. Wang J. Baroody F.M. Naclerio R.M. A randomized, double-blind, placebo-controlled trial of anti-IgE for chronic rhinosinusitis.Rhinology. 2010; 48: 318-324PubMed Google Scholar the current study demonstrates a significant reduction in endoscopically graded polyp size, which was confirmed by changes in Lund-MacKay sinus computed tomographic scores. Improvement was also seen in most of the secondary end points, including nasal and asthma symptoms and quality-of-life questionnaire scores. The significance of these results is enhanced by the fact that improvement in upper and lower airway disease was seen independently of systemic atopy, further supporting the potential significance of local IgE production in the airways.The therapeutic mainstays for the treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP) are oral and intranasal corticosteroids, with endoscopic sinus surgery as a backup and antibiotics for frequent infectious exacerbations. As the authors point out, the subset of patients with the most severe CRSwNP and consequently those most likely to lack success with this standard treatment regimen are patients with comorbid asthma.3Fokkens W.J. Lund V.J. Mullol J. Bachert C. Alobid I. Baroody F. et al.The European position paper on rhinosinusitis and nasal polyps.Rhinol Suppl. 2012; 23: 1-298Google Scholar Hence this study, which was also enhanced by enrollment of 8 of 15 patients with aspirin-exacerbated airway disease in the treatment arm, demonstrated efficacy in the most difficult-to-treat subset of patients with polyps. In general, use of anti-IgE has been restricted to patients with allergic asthma or patients with CRSwNP with systemic signs of atopy. Although allergic status was measured, inclusion criteria for this current report consisted of the concomitant presence of asthma and nasal polyposis only, and equal numbers of allergic and nonallergic patients were enrolled in the treatment arm; both subgroups responded equally well to the treatment. Patients with CRSwNP with comorbid asthma have a very high incidence of local IgE production in the polyp tissue independently of systemic IgE.4Lamblin C. Gosset P. Salez F. Vandezande L.M. Perez T. Darras J. et al.Eosinophilic airway inflammation in nasal polyposis.J Allergy Clin Immunol. 1999; 104: 85-92Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar Although not proved, because omalizumab was equally efficacious in both the allergic and nonallergic subsets in this study, the presumed mechanism of action was neutralization of IgE produced locally within the polyp tissue and possibly the peripheral lower respiratory tissues as well. It should be noted that anecdotal evidence exists to support the use of omalizumab in patients with nonallergic asthma as well.These encouraging results suggest that more widespread application of omalizumab for CRSwNP might be an option for the treatment of patients with recalcitrant CRSwNP, despite the expense and regardless of asthma status or systemic atopy. Comparison studies of the cost and durability of anti-IgE versus repetitive surgery might favor the former, depending on the severity of the nasal polyposis. Moreover, the durability of the polyp response to omalizumab is currently unclear, and chronic maintenance therapy might be unnecessary to control polyp growth. However, in addition to cost, the question of toxicity could limit broad application. The rationale for the use of systemic biologic agents for the treatment of severe asthma, which has an uncommon but not insignificant mortality, is more easily supported. Although the side effects of anti-IgE therapy in this report and others have generally been negligible, issues have been raised in regard to 3 main areas: malignancy, cardiovascular disease, and anaphylaxis.5Chipps B. Filiomeni M. Spector S. Omalizumab: an update on safety and efficacy in moderate to severe asthma.Allergy Asthma Proc. 2012; 33: 337-385Crossref Scopus (18) Google Scholar However, a recent report using pooled data from 67 phase I to IV clinical trials indicated no difference in the rate of malignancy in omalizumab-treated versus placebo-treated patients.6Busse W. Buhl R. Fernandez Vidaurre C. Blogg M. Zhu J. Eisner M. et al.Omalizumab and the risk of malignancy: results from a pooled analysis.J Allergy Clin Immunol. 2012; 129: 983-989Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar Data evaluating the long-term risk of malignancy and potential cardiovascular risks should be available soon because the EXCELS study has been completed recently.7Long A.A. Fish J.E. Rahamaoui A. Miller M.K. Bradley M.S. Taki H.N. Demeo A.N. et al.Baseline characteristics of patients enrolled in EXCELS: a cohort study.Ann Allergy Asthma Immunol. 2009; 103: 212-219Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar The incidence of anaphylaxis is approximately 0.2%, mandating administration in a health care setting.5Chipps B. Filiomeni M. Spector S. Omalizumab: an update on safety and efficacy in moderate to severe asthma.Allergy Asthma Proc. 2012; 33: 337-385Crossref Scopus (18) Google ScholarCurrent treatment protocols for chronic rhinosinusitis (CRS) with or without nasal polyps are based on expert guidelines rather than randomized phase III clinical trials. The resultant, widespread nonspecific management of CRS with antibiotics, corticosteroids, and surgery, as currently used in the United States, leaves us with substantial residual morbidity. Moreover, the effect of frequent oral antibiotic use for CRS exacerbations on microbial resistance rates within a population has not been fully evaluated but is likely substantial. Hence there appears to be a compelling need for new strategies, including biologic agents, to treat this common disorder. The publication by Gevaert et al1Gevaert P. Calus L. Van Zele T. Blomme K. De Ruyck N. Bauters W. et al.Omalizumab is effective in allergic and non-allergic patients with nasal polyps and asthma.J Allergy Clin Immunol. 2013; 131: 110-116Abstract Full Text Full Text PDF PubMed Scopus (480) Google Scholar of this phase II proof-of-concept study with omalizumab further opens the door to more innovative strategies for the management of CRS in general and CRSwNP in particular. Earlier phase II studies with anti–IL-5 antibodies for CRSwNP by the same group of investigators indicated polyp shrinkage in a little more than half of the patients.8Gevaert P. Lang-Loidolt D. Lackner A. Stammberger H. Staudinger H. Van Zele T. et al.Nasal IL-5 levels determine the response to anti-IL-5 treatment in patients with nasal polyps.J Allergy Clin Immunol. 2006; 118: 1133-1141Abstract Full Text Full Text PDF PubMed Scopus (333) Google Scholar, 9Gevaert P. Van Bruaene N. Cattaert T. Van Steen K. Van Zele T. Acke F. et al.Mepolizumab, a humanized anti-IL-5 mAb, as a treatment option for severe nasal polyposis.J Allergy Clin Immunol. 2011; 128: 989-995Abstract Full Text Full Text PDF PubMed Scopus (441) Google Scholar This subgroup of patients who responded to anti–IL-5 with polyp shrinkage also demonstrated a decrease in some of the indicators of TH2 inflammation in nasal secretions. The initial pilot trial suggested that nasal IL-5 levels could predict responders,8Gevaert P. Lang-Loidolt D. Lackner A. Stammberger H. Staudinger H. Van Zele T. et al.Nasal IL-5 levels determine the response to anti-IL-5 treatment in patients with nasal polyps.J Allergy Clin Immunol. 2006; 118: 1133-1141Abstract Full Text Full Text PDF PubMed Scopus (333) Google Scholar but the follow-up study9Gevaert P. Van Bruaene N. Cattaert T. Van Steen K. Van Zele T. Acke F. et al.Mepolizumab, a humanized anti-IL-5 mAb, as a treatment option for severe nasal polyposis.J Allergy Clin Immunol. 2011; 128: 989-995Abstract Full Text Full Text PDF PubMed Scopus (441) Google Scholar did not confirm this. Therefore despite the encouraging results, no clinical or laboratory parameter was identified that could predict therapeutic response and thereby enhance the success rate. Although it is difficult to compare these results using anti–IL-5 directly with the current study, omalizumab appeared to demonstrate substantially greater polyp shrinkage and subjective improvement, even when compared only with the anti–IL-5 responder subgroup. Larger phase III clinical trials with either biologic agent will be necessary to confirm efficacy and improved outcomes versus standard therapy.The use of mouse models and human trials with biologic agents have provided important insights into the pathophysiology of asthma.10Bochner B. Gleich G. What targeting eosinophils has taught us about their role in diseases.J Allergy Clin Immunol. 2010; 126: 16-25Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar Widely accepted mouse models for nasal polyposis or CRS do not exist, but human trials with anti-IgE and anti–IL-5 open lines of inquiry in regard to the pathophysiology of these disorders. Studies on the mechanism of action of omalizumab in asthmatic patients have indicated that this drug leads to a reduction in free circulating IgE levels, with secondary reductions in the high-affinity IgE receptors present on mast cells, basophils, and dendritic cells.11Avila P.C. Does anti-IgE therapy help in asthma? Efficacy and controversies.Annu Rev Med. 2007; 58: 185-203Crossref PubMed Scopus (32) Google Scholar In addition, reductions have also been observed in bronchial eosinophilia and TH2 cytokine levels.11Avila P.C. Does anti-IgE therapy help in asthma? Efficacy and controversies.Annu Rev Med. 2007; 58: 185-203Crossref PubMed Scopus (32) Google Scholar Interestingly, despite polyp shrinkage, this new study by Gevaert et al1Gevaert P. Calus L. Van Zele T. Blomme K. De Ruyck N. Bauters W. et al.Omalizumab is effective in allergic and non-allergic patients with nasal polyps and asthma.J Allergy Clin Immunol. 2013; 131: 110-116Abstract Full Text Full Text PDF PubMed Scopus (480) Google Scholar does not show the expected changes in nasal secretion levels of either eosinophil cationic protein or IL-5, suggesting that polyp eosinophilia, although not directly measured, is unchanged in treated patients. Studies in asthmatic patients have generally used longer treatment protocols however, and it is possible that longer durations of omalizumab treatment would reduce eosinophil cationic protein and peripheral eosinophilia in polyps as well. The authors have interpreted these results to suggest that the effect on nasal polyps (shrinkage) must primarily be through direct effects on IgE, IgE receptors, and presumably mast cells, as opposed to secondary reductions in eosinophilia. Although this is not completely clear, the current findings do suggest the hypothesis that polyp swelling might be more dependent on IgE and mast cell mediators as opposed to eosinophil degranulation. The greater reduction in polyp size in this study with anti-IgE in comparison with earlier trials with anti–IL-5 also provides some support to this hypothesis. Traditionally, the eosinophil has been considered the key cell type mediating tissue damage and polyp formation, but other recent reports have begun to re-evaluate the importance of mast cells in patients with CRSwNP.12Takabayashi T. Kato A. Peters A.T. Suh L. Carter R. Norton J. et al.Glandular mast cells with distinct phenotype are highly elevated in chronic rhinosinusitis with nasal polyps.J Allergy Clin Immunol. 2012; 130: 410-420.e5Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar, 13Schleimer R. Kato A. Kern R.C. Eosinophils in CRS.in: Lee J. Rosenberg H. Eosinophils in health and disease. Elsevier, Amsterdam2012Google Scholar Overall, however, this raises the therapeutic question of potentially targeting both mast cells and eosinophils for the management of CRSwNP and asthma as well. To this point, the Siglec (sialic acid immunoglobulin-like lectins) group of cell-surface proteins might present just such a target. Among them, Siglec-8 is uniquely expressed by human eosinophils, mast cells, and basophils. Engaging this structure with antibodies has the therapeutic potential to neutralize all 3 cell types, suggesting the tantalizing potential to address a wide array of TH2 disorders.14Kiwamoto T. Kawasaki N. Paulson J.C. Bochner B.S. Siglec-8 as a drugable target to treat eosinophil and mast cell-associated conditions.Pharmacol Ther. 2012; 135: 327-336Crossref PubMed Scopus (128) Google Scholar The study by Gevaert et al1Gevaert P. Calus L. Van Zele T. Blomme K. De Ruyck N. Bauters W. et al.Omalizumab is effective in allergic and non-allergic patients with nasal polyps and asthma.J Allergy Clin Immunol. 2013; 131: 110-116Abstract Full Text Full Text PDF PubMed Scopus (480) Google Scholar reports positive results for a randomized, double-blind, placebo-controlled phase II trial using omalizumab for the management of allergic and nonallergic patients with nasal polyps and asthma. The primary end point was reduction in the nasal polyp score, and in contrast to an earlier, underpowered negative trial with omalizumab,2Pinto J.M. Mehta N. DiTineo M. Wang J. Baroody F.M. Naclerio R.M. A randomized, double-blind, placebo-controlled trial of anti-IgE for chronic rhinosinusitis.Rhinology. 2010; 48: 318-324PubMed Google Scholar the current study demonstrates a significant reduction in endoscopically graded polyp size, which was confirmed by changes in Lund-MacKay sinus computed tomographic scores. Improvement was also seen in most of the secondary end points, including nasal and asthma symptoms and quality-of-life questionnaire scores. The significance of these results is enhanced by the fact that improvement in upper and lower airway disease was seen independently of systemic atopy, further supporting the potential significance of local IgE production in the airways. The therapeutic mainstays for the treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP) are oral and intranasal corticosteroids, with endoscopic sinus surgery as a backup and antibiotics for frequent infectious exacerbations. As the authors point out, the subset of patients with the most severe CRSwNP and consequently those most likely to lack success with this standard treatment regimen are patients with comorbid asthma.3Fokkens W.J. Lund V.J. Mullol J. Bachert C. Alobid I. Baroody F. et al.The European position paper on rhinosinusitis and nasal polyps.Rhinol Suppl. 2012; 23: 1-298Google Scholar Hence this study, which was also enhanced by enrollment of 8 of 15 patients with aspirin-exacerbated airway disease in the treatment arm, demonstrated efficacy in the most difficult-to-treat subset of patients with polyps. In general, use of anti-IgE has been restricted to patients with allergic asthma or patients with CRSwNP with systemic signs of atopy. Although allergic status was measured, inclusion criteria for this current report consisted of the concomitant presence of asthma and nasal polyposis only, and equal numbers of allergic and nonallergic patients were enrolled in the treatment arm; both subgroups responded equally well to the treatment. Patients with CRSwNP with comorbid asthma have a very high incidence of local IgE production in the polyp tissue independently of systemic IgE.4Lamblin C. Gosset P. Salez F. Vandezande L.M. Perez T. Darras J. et al.Eosinophilic airway inflammation in nasal polyposis.J Allergy Clin Immunol. 1999; 104: 85-92Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar Although not proved, because omalizumab was equally efficacious in both the allergic and nonallergic subsets in this study, the presumed mechanism of action was neutralization of IgE produced locally within the polyp tissue and possibly the peripheral lower respiratory tissues as well. It should be noted that anecdotal evidence exists to support the use of omalizumab in patients with nonallergic asthma as well. These encouraging results suggest that more widespread application of omalizumab for CRSwNP might be an option for the treatment of patients with recalcitrant CRSwNP, despite the expense and regardless of asthma status or systemic atopy. Comparison studies of the cost and durability of anti-IgE versus repetitive surgery might favor the former, depending on the severity of the nasal polyposis. Moreover, the durability of the polyp response to omalizumab is currently unclear, and chronic maintenance therapy might be unnecessary to control polyp growth. However, in addition to cost, the question of toxicity could limit broad application. The rationale for the use of systemic biologic agents for the treatment of severe asthma, which has an uncommon but not insignificant mortality, is more easily supported. Although the side effects of anti-IgE therapy in this report and others have generally been negligible, issues have been raised in regard to 3 main areas: malignancy, cardiovascular disease, and anaphylaxis.5Chipps B. Filiomeni M. Spector S. Omalizumab: an update on safety and efficacy in moderate to severe asthma.Allergy Asthma Proc. 2012; 33: 337-385Crossref Scopus (18) Google Scholar However, a recent report using pooled data from 67 phase I to IV clinical trials indicated no difference in the rate of malignancy in omalizumab-treated versus placebo-treated patients.6Busse W. Buhl R. Fernandez Vidaurre C. Blogg M. Zhu J. Eisner M. et al.Omalizumab and the risk of malignancy: results from a pooled analysis.J Allergy Clin Immunol. 2012; 129: 983-989Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar Data evaluating the long-term risk of malignancy and potential cardiovascular risks should be available soon because the EXCELS study has been completed recently.7Long A.A. Fish J.E. Rahamaoui A. Miller M.K. Bradley M.S. Taki H.N. Demeo A.N. et al.Baseline characteristics of patients enrolled in EXCELS: a cohort study.Ann Allergy Asthma Immunol. 2009; 103: 212-219Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar The incidence of anaphylaxis is approximately 0.2%, mandating administration in a health care setting.5Chipps B. Filiomeni M. Spector S. Omalizumab: an update on safety and efficacy in moderate to severe asthma.Allergy Asthma Proc. 2012; 33: 337-385Crossref Scopus (18) Google Scholar Current treatment protocols for chronic rhinosinusitis (CRS) with or without nasal polyps are based on expert guidelines rather than randomized phase III clinical trials. The resultant, widespread nonspecific management of CRS with antibiotics, corticosteroids, and surgery, as currently used in the United States, leaves us with substantial residual morbidity. Moreover, the effect of frequent oral antibiotic use for CRS exacerbations on microbial resistance rates within a population has not been fully evaluated but is likely substantial. Hence there appears to be a compelling need for new strategies, including biologic agents, to treat this common disorder. The publication by Gevaert et al1Gevaert P. Calus L. Van Zele T. Blomme K. De Ruyck N. Bauters W. et al.Omalizumab is effective in allergic and non-allergic patients with nasal polyps and asthma.J Allergy Clin Immunol. 2013; 131: 110-116Abstract Full Text Full Text PDF PubMed Scopus (480) Google Scholar of this phase II proof-of-concept study with omalizumab further opens the door to more innovative strategies for the management of CRS in general and CRSwNP in particular. Earlier phase II studies with anti–IL-5 antibodies for CRSwNP by the same group of investigators indicated polyp shrinkage in a little more than half of the patients.8Gevaert P. Lang-Loidolt D. Lackner A. Stammberger H. Staudinger H. Van Zele T. et al.Nasal IL-5 levels determine the response to anti-IL-5 treatment in patients with nasal polyps.J Allergy Clin Immunol. 2006; 118: 1133-1141Abstract Full Text Full Text PDF PubMed Scopus (333) Google Scholar, 9Gevaert P. Van Bruaene N. Cattaert T. Van Steen K. Van Zele T. Acke F. et al.Mepolizumab, a humanized anti-IL-5 mAb, as a treatment option for severe nasal polyposis.J Allergy Clin Immunol. 2011; 128: 989-995Abstract Full Text Full Text PDF PubMed Scopus (441) Google Scholar This subgroup of patients who responded to anti–IL-5 with polyp shrinkage also demonstrated a decrease in some of the indicators of TH2 inflammation in nasal secretions. The initial pilot trial suggested that nasal IL-5 levels could predict responders,8Gevaert P. Lang-Loidolt D. Lackner A. Stammberger H. Staudinger H. Van Zele T. et al.Nasal IL-5 levels determine the response to anti-IL-5 treatment in patients with nasal polyps.J Allergy Clin Immunol. 2006; 118: 1133-1141Abstract Full Text Full Text PDF PubMed Scopus (333) Google Scholar but the follow-up study9Gevaert P. Van Bruaene N. Cattaert T. Van Steen K. Van Zele T. Acke F. et al.Mepolizumab, a humanized anti-IL-5 mAb, as a treatment option for severe nasal polyposis.J Allergy Clin Immunol. 2011; 128: 989-995Abstract Full Text Full Text PDF PubMed Scopus (441) Google Scholar did not confirm this. Therefore despite the encouraging results, no clinical or laboratory parameter was identified that could predict therapeutic response and thereby enhance the success rate. Although it is difficult to compare these results using anti–IL-5 directly with the current study, omalizumab appeared to demonstrate substantially greater polyp shrinkage and subjective improvement, even when compared only with the anti–IL-5 responder subgroup. Larger phase III clinical trials with either biologic agent will be necessary to confirm efficacy and improved outcomes versus standard therapy. The use of mouse models and human trials with biologic agents have provided important insights into the pathophysiology of asthma.10Bochner B. Gleich G. What targeting eosinophils has taught us about their role in diseases.J Allergy Clin Immunol. 2010; 126: 16-25Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar Widely accepted mouse models for nasal polyposis or CRS do not exist, but human trials with anti-IgE and anti–IL-5 open lines of inquiry in regard to the pathophysiology of these disorders. Studies on the mechanism of action of omalizumab in asthmatic patients have indicated that this drug leads to a reduction in free circulating IgE levels, with secondary reductions in the high-affinity IgE receptors present on mast cells, basophils, and dendritic cells.11Avila P.C. Does anti-IgE therapy help in asthma? Efficacy and controversies.Annu Rev Med. 2007; 58: 185-203Crossref PubMed Scopus (32) Google Scholar In addition, reductions have also been observed in bronchial eosinophilia and TH2 cytokine levels.11Avila P.C. Does anti-IgE therapy help in asthma? Efficacy and controversies.Annu Rev Med. 2007; 58: 185-203Crossref PubMed Scopus (32) Google Scholar Interestingly, despite polyp shrinkage, this new study by Gevaert et al1Gevaert P. Calus L. Van Zele T. Blomme K. De Ruyck N. Bauters W. et al.Omalizumab is effective in allergic and non-allergic patients with nasal polyps and asthma.J Allergy Clin Immunol. 2013; 131: 110-116Abstract Full Text Full Text PDF PubMed Scopus (480) Google Scholar does not show the expected changes in nasal secretion levels of either eosinophil cationic protein or IL-5, suggesting that polyp eosinophilia, although not directly measured, is unchanged in treated patients. Studies in asthmatic patients have generally used longer treatment protocols however, and it is possible that longer durations of omalizumab treatment would reduce eosinophil cationic protein and peripheral eosinophilia in polyps as well. The authors have interpreted these results to suggest that the effect on nasal polyps (shrinkage) must primarily be through direct effects on IgE, IgE receptors, and presumably mast cells, as opposed to secondary reductions in eosinophilia. Although this is not completely clear, the current findings do suggest the hypothesis that polyp swelling might be more dependent on IgE and mast cell mediators as opposed to eosinophil degranulation. The greater reduction in polyp size in this study with anti-IgE in comparison with earlier trials with anti–IL-5 also provides some support to this hypothesis. Traditionally, the eosinophil has been considered the key cell type mediating tissue damage and polyp formation, but other recent reports have begun to re-evaluate the importance of mast cells in patients with CRSwNP.12Takabayashi T. Kato A. Peters A.T. Suh L. Carter R. Norton J. et al.Glandular mast cells with distinct phenotype are highly elevated in chronic rhinosinusitis with nasal polyps.J Allergy Clin Immunol. 2012; 130: 410-420.e5Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar, 13Schleimer R. Kato A. Kern R.C. Eosinophils in CRS.in: Lee J. Rosenberg H. Eosinophils in health and disease. Elsevier, Amsterdam2012Google Scholar Overall, however, this raises the therapeutic question of potentially targeting both mast cells and eosinophils for the management of CRSwNP and asthma as well. To this point, the Siglec (sialic acid immunoglobulin-like lectins) group of cell-surface proteins might present just such a target. Among them, Siglec-8 is uniquely expressed by human eosinophils, mast cells, and basophils. Engaging this structure with antibodies has the therapeutic potential to neutralize all 3 cell types, suggesting the tantalizing potential to address a wide array of TH2 disorders.14Kiwamoto T. Kawasaki N. Paulson J.C. Bochner B.S. Siglec-8 as a drugable target to treat eosinophil and mast cell-associated conditions.Pharmacol Ther. 2012; 135: 327-336Crossref PubMed Scopus (128) Google Scholar Omalizumab is effective in allergic and nonallergic patients with nasal polyps and asthmaJournal of Allergy and Clinical ImmunologyVol. 131Issue 1PreviewAdult patients with nasal polyps often have comorbid asthma, adding to the serious effect on the quality of life of these patients. Nasal polyps and asthma might represent a therapeutic challenge; inflammation in both diseases shares many features, such as airway eosinophilia, local IgE formation, and a TH2 cytokine profile. Omalizumab is a human anti-IgE mAb with proved efficacy in patients with severe allergic asthma. Omalizumab could be a treatment option for patients with nasal polyps and asthma. Full-Text PDF Should clinicians use omalizumab for the treatment of nasal polyps?Journal of Allergy and Clinical ImmunologyVol. 132Issue 1PreviewWe read with interest the article entitled “Omalizumab is effective in allergic and nonallergic patients with nasal polyps and asthma” by Gevaert et al1 and the accompanying editorial by Kern.2 The study provides excellent clinical and biomarker data in a small group of patients, strongly implicating that IgE plays a role in the pathophysiology of nasal polyps in asthmatic individuals with and without positive skin test results. Full-Text PDF