Drugs

, Volume 77, Issue 16, pp 1713–1721 | Cite as

Pharmacological Management of Chronic Rhinosinusitis: Current and Evolving Treatments

  • Daniel M. Beswick
  • Stacey T. Gray
  • Timothy L. Smith
Leading Article

Abstract

Chronic rhinosinusitis (CRS) is an inflammatory sinonasal condition with multiple etiologic factors that is associated with a vast economic cost. Treatment is most frequently pharmacologic and has centered on agents that ameliorate inflammation, decrease bacterial or pathogen load, and facilitate egress of mucus or purulence from the sinonasal cavity. Nasal saline irrigations, topical nasal steroids, certain antibiotics, and systemic steroids have shown some efficacy in the management of CRS. Recently, biologic therapeutics that target specific inflammatory pathways associated with subsets of CRS have been developed and evaluated. Early data evaluating these biologic treatments suggest a potential role in treating a subset of CRS with refractory, poorly controlled disease. Additional studies are necessary to identify which patients would benefit most from biologic therapies and to assess the cost of these therapies compared with the benefit they provide. This review describes the pathophysiology of CRS and summarizes both established and novel biologic pharmacologic treatments.

Notes

Compliance with Ethical Standards

Funding

No sources of funding were directly used for this project.

Conflict of interest

Timothy L. Smith was previously a consultant for Intersect ENT. This relationship ended in 2015. He is supported by a grant for this investigation from the National Institute on Deafness and Other Communication Disorders (NIDCD), one of the National Institutes of Health, Bethesda, MD, USA (R01 DC005805; PI/PD: TL Smith). Public clinical trial registration (http://www.clinicaltrials.gov) ID: NCT01332136. This funding organization did not contribute to the design or conduct of this study; collection, management, analysis, or interpretation of the data; and preparation, review, approval or decision to submit this manuscript for publication.

References

  1. 1.
    Bhattacharyya N. Incremental health care utilization and expenditures for chronic rhinosinusitis in the United States. Ann Otol Rhinol Laryngol. 2011;120(7):423–7.CrossRefPubMedGoogle Scholar
  2. 2.
    Orlandi RR, Kingdom TT, Hwang PH, Smith TL, Alt JA, Baroody FM, et al. International consensus statement on allergy and rhinology: rhinosinusitis. Int Forum Allergy Rhinol. 2016;6(Suppl 1):S22–209.PubMedGoogle Scholar
  3. 3.
    Akdis CA, Bachert C, Cingi C, Dykewicz MS, Hellings PW, Naclerio RM, et al. Endotypes and phenotypes of chronic rhinosinusitis: a PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology. J Allergy Clin Immunol. 2013;131(6):1479–90.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Lam K, Kern RC, Luong A. Is there a future for biologics in the management of chronic rhinosinusitis? Int Forum Allergy Rhinol. 2016;6(9):935–42.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Amini-Vaughan ZJ, Martinez-Moczygemba M, Huston DP. Therapeutic strategies for harnessing human eosinophils in allergic inflammation, hypereosinophilic disorders, and cancer. Curr Allergy Asthma Rep. 2012;12(5):402–12.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Zhang N, Van Zele T, Perez-Novo C, Van Bruaene N, Holtappels G, DeRuyck N, et al. Different types of T-effector cells orchestrate mucosal inflammation in chronic sinus disease. J Allergy Clin Immunol. 2008;122(5):961–8.CrossRefPubMedGoogle Scholar
  7. 7.
    Oue S, Ramezanpour M, Paramasivan S, Miljkovic D, Cooksley CM, Bassiouni A, et al. Increased IL-13 expression is independently associated with neo-osteogenesis in patients with chronic rhinosinusitis. J Allergy Clin Immunol. 2017. doi: 10.1016/j.jaci.2017.05.021
  8. 8.
    Palmqvist P, Lundberg P, Persson E, Johansson A, Lundgren I, Lie A, et al. Inhibition of hormone and cytokine-stimulated osteoclastogenesis and bone resorption by interleukin-4 and interleukin-13 is associated with increased osteoprotegerin and decreased RANKL and RANK in a STAT6-dependent pathway. J Biol Chem. 2006;281(5):2414–29.CrossRefPubMedGoogle Scholar
  9. 9.
    Harvey R, Hannan SA, Badia L, Scadding G. Nasal saline irrigations for the symptoms of chronic rhinosinusitis. Cochrane Database Syst Rev. 2007;18(3):CD006394. doi: 10.1002/14651858.CD006394.pub2.Google Scholar
  10. 10.
    Rudmik L, Hoy M, Schlosser RJ, Harvey RJ, Welch KC, Lund V, et al. Topical therapies in the management of chronic rhinosinusitis: an evidence-based review with recommendations. Int Forum Allergy Rhinol. 2013;3(4):281–98.CrossRefPubMedGoogle Scholar
  11. 11.
    Pynnonen MA, Mukerji SS, Kim HM, Adams ME, Terrell JE. Nasal saline for chronic sinonasal symptoms: a randomized controlled trial. Arch Otolaryngol Head Neck Surg. 2007;133(11):1115–20.CrossRefPubMedGoogle Scholar
  12. 12.
    Liang J, Lane AP. Topical drug delivery for chronic rhinosinusitis. Curr Otorhinolaryngol Rep. 2013;1(1):51–60.CrossRefPubMedGoogle Scholar
  13. 13.
  14. 14.
    Sastre J, Mosges R. Local and systemic safety of intranasal corticosteroids. J Investig Allergol Clin Immunol. 2012;22(1):1–12.PubMedGoogle Scholar
  15. 15.
    Chong LY, Head K, Hopkins C, Philpott C, Schilder AG, Burton MJ. Intranasal steroids versus placebo or no intervention for chronic rhinosinusitis. Cochrane Database Syst Rev. 2016;4:CD011996.PubMedGoogle Scholar
  16. 16.
    Chong LY, Head K, Hopkins C, Philpott C, Burton MJ, Schilder AG. Different types of intranasal steroids for chronic rhinosinusitis. Cochrane Database Syst Rev. 2016;4:CD011993. doi: 10.1002/14651858.CD011993.pub2.PubMedGoogle Scholar
  17. 17.
    Head K, Chong LY, Hopkins C, Philpott C, Burton MJ, Schilder AG. Short-course oral steroids alone for chronic rhinosinusitis. Cochrane Database Syst Rev. 2016;4:CD011991. doi: 10.1002/14651858.CD011991.pub2.PubMedGoogle Scholar
  18. 18.
    Leung RM, Dinnie K, Smith TL. When do the risks of repeated courses of corticosteroids exceed the risks of surgery? Int Forum Allergy Rhinol. 2014;4(11):871–6.CrossRefPubMedGoogle Scholar
  19. 19.
    Harvey RJ, Wallwork BD, Lund VJ. Anti-inflammatory effects of macrolides: applications in chronic rhinosinusitis. Immunol Allergy Clin North Am. 2009;29(4):689–703.CrossRefPubMedGoogle Scholar
  20. 20.
    Head K, Chong LY, Piromchai P, Hopkins C, Philpott C, Schilder AG, et al. Systemic and topical antibiotics for chronic rhinosinusitis. Cochrane Database Syst Rev. 2016;4:CD011994. doi: 10.1002/14651858.CD011994.pub2.PubMedGoogle Scholar
  21. 21.
    Mosholder AD, Mathew J, Alexander JJ, Smith H, Nambiar S. Cardiovascular risks with azithromycin and other antibacterial drugs. N Engl J Med. 2013;368(18):1665–8.CrossRefPubMedGoogle Scholar
  22. 22.
    Smith SS, Evans CT, Tan BK, Chandra RK, Smith SB, Kern R. National burden of antibiotic use for adult rhinosinusitis. J Allergy Clin Immunol. 2013;132(5):1230–2.CrossRefPubMedGoogle Scholar
  23. 23.
    Desrosiers MY, Salas-Prato M. Treatment of chronic rhinosinusitis refractory to other treatments with topical antibiotic therapy delivered by means of a large-particle nebulizer: results of a controlled trial. Otolaryngol Head Neck Surg. 2001;125(3):265–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Wei JL, Sykes KJ, Johnson P, He J, Mayo MS. Safety and efficacy of once-daily nasal irrigation for the treatment of pediatric chronic rhinosinusitis. Laryngoscope. 2011;121(9):1989–2000.PubMedGoogle Scholar
  25. 25.
    Jervis-Bardy J, Boase S, Psaltis A, Foreman A, Wormald PJ. A randomized trial of mupirocin sinonasal rinses versus saline in surgically recalcitrant staphylococcal chronic rhinosinusitis. Laryngoscope. 2012;122(10):2148–53.CrossRefPubMedGoogle Scholar
  26. 26.
    Lanza DC, Dhong HJ, Tantilipikorn P, Tanabodee J, Nadel DM, Kennedy DW. Fungus and chronic rhinosinusitis: from bench to clinical understanding. Ann Otol Rhinol Laryngol Suppl. 2006;196:27–34.CrossRefPubMedGoogle Scholar
  27. 27.
    Sacks PL, Harvey RJ, Rimmer J, Gallagher RM, Sacks R. Topical and systemic antifungal therapy for the symptomatic treatment of chronic rhinosinusitis. Cochrane Database Syst Rev. 2011;8:CD008263. doi: 10.1002/14651858.CD008263.pub2.Google Scholar
  28. 28.
    Holgate ST, Peters-Golden M, Panettieri RA, Henderson WR Jr. Roles of cysteinyl leukotrienes in airway inflammation, smooth muscle function, and remodeling. J Allergy Clin Immunol. 2003;111(1 Suppl):S18–34. doi: 10.1067/mai.2003.25.CrossRefPubMedGoogle Scholar
  29. 29.
    Smith TL, Sautter NB. Is montelukast indicated for treatment of chronic rhinosinusitis with polyposis? Laryngoscope. 2014;124(8):1735–6.CrossRefPubMedGoogle Scholar
  30. 30.
    Garcia-Marcos L, Schuster A, Perez-Yarza EG. Benefit-risk assessment of antileukotrienes in the management of asthma. Drug Saf. 2003;26(7):483–518.CrossRefPubMedGoogle Scholar
  31. 31.
    Wentzel JL, Soler ZM, DeYoung K, Nguyen SA, Lohia S, Schlosser RJ. Leukotriene antagonists in nasal polyposis: a meta-analysis and systematic review. Am J Rhinol Allergy. 2013;27(6):482–9.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F, et al. EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012. A summary for otorhinolaryngologists. Rhinology. 2012;50(1):1–12.PubMedGoogle Scholar
  33. 33.
    Dahlen B, Nizankowska E, Szczeklik A, Zetterstrom O, Bochenek G, Kumlin M, et al. Benefits from adding the 5-lipoxygenase inhibitor zileuton to conventional therapy in aspirin-intolerant asthmatics. Am J Respir Crit Care Med. 1998;157(4 Pt 1):1187–94.CrossRefPubMedGoogle Scholar
  34. 34.
    Hopkins C, Andrews P, Holy CE. Does time to endoscopic sinus surgery impact outcomes in chronic rhinosinusitis? Retrospective analysis using the UK clinical practice research data. Rhinology. 2015;53(1):18–24.PubMedGoogle Scholar
  35. 35.
    Hopkins C, Rimmer J, Lund VJ. Does time to endoscopic sinus surgery impact outcomes in Chronic Rhinosinusitis? Prospective findings from the National Comparative Audit of Surgery for Nasal Polyposis and Chronic Rhinosinusitis. Rhinology. 2015;53(1):10–7.PubMedGoogle Scholar
  36. 36.
    Benninger MS, Sindwani R, Holy CE, Hopkins C. Early versus delayed endoscopic sinus surgery in patients with chronic rhinosinusitis: impact on health care utilization. Otolaryngol Head Neck Surg. 2015;152(3):546–52.CrossRefPubMedGoogle Scholar
  37. 37.
    Smith KA, Rudmik L. Impact of continued medical therapy in patients with refractory chronic rhinosinusitis. Int Forum Allergy Rhinol. 2014;4(1):34–8.CrossRefPubMedGoogle Scholar
  38. 38.
    Patel ZM, Thamboo A, Rudmik L, Nayak JV, Smith TL, Hwang PH. Surgical therapy vs continued medical therapy for medically refractory chronic rhinosinusitis: a systematic review and meta-analysis. Int Forum Allergy Rhinol. 2017;7(2):119–27.CrossRefPubMedGoogle Scholar
  39. 39.
    Chin D, Harvey RJ. Nasal polyposis: an inflammatory condition requiring effective anti-inflammatory treatment. Curr Opin Otolaryngol Head Neck Surg. 2013;21(1):23–30.CrossRefPubMedGoogle Scholar
  40. 40.
    Rudmik L, Smith TL. Evidence-based practice: postoperative care in endoscopic sinus surgery. Otolaryngol Clin North Am. 2012;45(5):1019–32.CrossRefPubMedGoogle Scholar
  41. 41.
    Rudmik L, Soler ZM, Orlandi RR, Stewart MG, Bhattacharyya N, Kennedy DW, et al. Early postoperative care following endoscopic sinus surgery: an evidence-based review with recommendations. Int Forum Allergy Rhinol. 2011;1(6):417–30.CrossRefPubMedGoogle Scholar
  42. 42.
    Mendelsohn D, Jeremic G, Wright ED, Rotenberg BW. Revision rates after endoscopic sinus surgery: a recurrence analysis. Ann Otol Rhinol Laryngol. 2011;120(3):162–6.CrossRefPubMedGoogle Scholar
  43. 43.
    Fajt ML, Wenzel SE. Biologic therapy in asthma: entering the new age of personalized medicine. J Asthma. 2014;51(7):669–76.CrossRefPubMedGoogle Scholar
  44. 44.
    Bachert C, Holtappels G. Pathophysiology of chronic rhinosinusitis, pharmaceutical therapy options. GMS Curr Top Otorhinolaryngol Head Neck Surg. 2015;14:Doc09.PubMedPubMedCentralGoogle Scholar
  45. 45.
    Bachert C, Zhang N. Chronic rhinosinusitis and asthma: novel understanding of the role of IgE ‘above atopy’. J Intern Med. 2012;272(2):133–43.CrossRefPubMedGoogle Scholar
  46. 46.
    Strunk RC, Bloomberg GR. Omalizumab for asthma. N Engl J Med. 2006;354(25):2689–95.CrossRefPubMedGoogle Scholar
  47. 47.
    Presta LG, Lahr SJ, Shields RL, Porter JP, Gorman CM, Fendly BM, et al. Humanization of an antibody directed against IgE. J Immunol. 1993;151(5):2623–32.PubMedGoogle Scholar
  48. 48.
    Casale TB, Condemi J, LaForce C, Nayak A, Rowe M, Watrous M, et al. Effect of omalizumab on symptoms of seasonal allergic rhinitis: a randomized controlled trial. JAMA. 2001;286(23):2956–67.CrossRefPubMedGoogle Scholar
  49. 49.
    Chervinsky P, Casale T, Townley R, Tripathy I, Hedgecock S, Fowler-Taylor A, et al. Omalizumab, an anti-IgE antibody, in the treatment of adults and adolescents with perennial allergic rhinitis. Ann Allergy Asthma Immunol. 2003;91(2):160–7.CrossRefPubMedGoogle Scholar
  50. 50.
    Grundmann SA, Hemfort PB, Luger TA, Brehler R. Anti-IgE (omalizumab): a new therapeutic approach for chronic rhinosinusitis. J Allergy Clin Immunol. 2008;121(1):257–8.CrossRefPubMedGoogle Scholar
  51. 51.
    Mendez R. Omalizumab induces resolution of fungal sinusitis in a 15 year old asthmatic patient. J Allergy Clin Immunol. 2006;117(2 Suppl):S8.CrossRefGoogle Scholar
  52. 52.
    Penn R, Mikula S. The role of anti-IgE immunoglobulin therapy in nasal polyposis: a pilot study. Am J Rhinol. 2007;21(4):428–32.CrossRefPubMedGoogle Scholar
  53. 53.
    Pinto JM, Mehta N, DiTineo M, Wang J, Baroody FM, Naclerio RM. A randomized, double-blind, placebo-controlled trial of anti-IgE for chronic rhinosinusitis. Rhinology. 2010;48(3):318–24.PubMedGoogle Scholar
  54. 54.
    Gevaert P, Calus L, Van Zele T, Blomme K, De Ruyck N, Bauters W, et al. Omalizumab is effective in allergic and nonallergic patients with nasal polyps and asthma. J Allergy Clin Immunol. 2013;131(1):110–116e1.CrossRefPubMedGoogle Scholar
  55. 55.
    Subcutaneous Omalizumab for Treatment of Chronic Rhinosinusitis With Nasal Polyposis. ClinicalTrials.gov Identifier NCT01066104. https://clinicaltrials.gov/ct2/show/results/NCT01066104?term=omalizumab+nasal&rank=2&sect=X7016. Accessed 20 May 2017.
  56. 56.
    Chandra RK, Clavenna M, Samuelson M, Tanner SB, Turner JH. Impact of omalizumab therapy on medication requirements for chronic rhinosinusitis. Int Forum Allergy Rhinol. 2016;6(5):472–7.CrossRefPubMedGoogle Scholar
  57. 57.
    Arm JP, Bottoli I, Skerjanec A, Floch D, Groenewegen A, Maahs S, et al. Pharmacokinetics, pharmacodynamics and safety of QGE031 (ligelizumab), a novel high-affinity anti-IgE antibody, in atopic subjects. Clin Exp Allergy. 2014;44(11):1371–85.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Gauvreau GM, Arm JP, Boulet LP, Leigh R, Cockcroft DW, Davis BE, et al. Efficacy and safety of multiple doses of QGE031 (ligelizumab) versus omalizumab and placebo in inhibiting allergen-induced early asthmatic responses. J Allergy Clin Immunol. 2016;138(4):1051–9.CrossRefPubMedGoogle Scholar
  59. 59.
    Bachert C, Zhang L, Gevaert P. Current and future treatment options for adult chronic rhinosinusitis: focus on nasal polyposis. J Allergy Clin Immunol. 2015;136(6):1431–40 (quiz 41).CrossRefPubMedGoogle Scholar
  60. 60.
    Cao PP, Li HB, Wang BF, Wang SB, You XJ, Cui YH et al. Distinct immunopathologic characteristics of various types of chronic rhinosinusitis in adult Chinese. J Allergy Clin Immunol. 2009;124(3):478–84, 484.e1–2.Google Scholar
  61. 61.
    Hamilos DL, Leung DY, Wood R, Cunningham L, Bean DK, Yasruel Z, et al. Evidence for distinct cytokine expression in allergic versus nonallergic chronic sinusitis. J Allergy Clin Immunol. 1995;96(4):537–44.CrossRefPubMedGoogle Scholar
  62. 62.
    Simon H, Yousefi S, Schranz C, Schapowal A, Bachert C, Blaser K. Direct demonstration of delayed eosinophil apoptosis as a mechanism causing tissue eosinophilia. J Immunol. 1997;158(8):3902–8.PubMedGoogle Scholar
  63. 63.
  64. 64.
    Gevaert 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(5):1133–41.CrossRefPubMedGoogle Scholar
  65. 65.
    Effect of Reslizumab in Chronic Rhinosinusitis. Clinical Trials.gov Identifier NCT02799446. 2017. https://clinicaltrials.gov/ct2/show/study/NCT02799446?term=reslizumab+nasal&rank=1. Accessed 22 Aug 2017
  66. 66.
  67. 67.
    Gevaert 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(5):989–95.e1–8.Google Scholar
  68. 68.
    Mepolizumab in Nasal Polyposis. Clinical Trials.gov Identifier NCT01362244. 2016. https://clinicaltrials.gov/ct2/show/study/NCT01362244?term=mepolizumab+nasal+polyps&rank=2&sect=X10256. Accessed 20 May 2017.
  69. 69.
    Effect of Mepolizumab in Severe Bilateral Nasal Polyps. ClinicalTrials.gov Identifier NCT03085797. https://clinicaltrials.gov/ct2/show/record/NCT03085797. Accessed 9 Aug 2017.
  70. 70.
    Kolbeck R, Kozhich A, Koike M, Peng L, Andersson CK, Damschroder MM et al. MEDI-563, a humanized anti-IL-5 receptor alpha mAb with enhanced antibody-dependent cell-mediated cytotoxicity function. J Allergy Clin Immunol. 2010;125(6):1344–53.e2.Google Scholar
  71. 71.
    Molfino NA, Gossage D, Kolbeck R, Parker JM, Geba GP. Molecular and clinical rationale for therapeutic targeting of interleukin-5 and its receptor. Clin Exp Allergy. 2012;42(5):712–37.CrossRefPubMedGoogle Scholar
  72. 72.
    Giannetti MP, Cardet JC. Interleukin-5 antagonists usher in a new generation of asthma therapy. Curr Allergy Asthma Rep. 2016;16(11):80.CrossRefPubMedGoogle Scholar
  73. 73.
    Study of Benralizumab (KHK4563) in Patients With Eosinophilic Chronic Rhinosinusitis. ClinicalTrials.gov Identifier: NCT02772419. https://clinicaltrials.gov/ct2/show/study/NCT02772419. Accessed 9 Aug 2017.
  74. 74.
    Vatrella A, Fabozzi I, Calabrese C, Maselli R, Pelaia G. Dupilumab: a novel treatment for asthma. J Asthma Allergy. 2014;7:123–30.CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Wenzel S, Ford L, Pearlman D, Spector S, Sher L, Skobieranda F, et al. Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med. 2013;368(26):2455–66.CrossRefPubMedGoogle Scholar
  76. 76.
  77. 77.
    Bachert C, Mannent L, Naclerio RM, Mullol J, Ferguson BJ, Gevaert P, et al. Effect of subcutaneous dupilumab on nasal polyp burden in patients with chronic sinusitis and nasal polyposis: a randomized clinical trial. JAMA. 2016;315(5):469–79.CrossRefPubMedGoogle Scholar
  78. 78.
    Rhinologic disorders: a health priority for the future. 26th Congress of the European Rhinologic Society; 3–7 July 2016; Stockholm.Google Scholar
  79. 79.
    A Controlled Clinical Study of Dupilumab in Patients With Nasal Polyps (SINUS-24). ClinicalTrials.gov Identifier: NCT02912468. https://clinicaltrials.gov/ct2/show/NCT02912468. Accessed 9 Aug 2017.
  80. 80.
    Controlled Clinical Study of Dupilumab in Patients With Nasal Polyps (SINUS-52). ClinicalTrials.gov Identifier: NCT02898454. https://clinicaltrials.gov/ct2/show/record/NCT02898454. Accessed 9 Aug 2017.
  81. 81.
    Bagnasco D, Ferrando M, Varricchi G, Passalacqua G, Canonica GW. A critical evaluation of anti-IL-13 and anti-IL-4 strategies in severe asthma. Int Arch Allergy Immunol. 2016;170(2):122–31.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Daniel M. Beswick
    • 1
  • Stacey T. Gray
    • 2
    • 3
  • Timothy L. Smith
    • 1
  1. 1.Department of OtolaryngologyOregon Health and Science UniversityPortlandUSA
  2. 2.Department of OtolaryngologyHarvard Medical SchoolBostonUSA
  3. 3.Department of OtolaryngologyMassachusetts Eye and Ear InfirmaryBostonUSA

Personalised recommendations