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Good clinical practice or a tool for marketing?
Guest editorial
Good clinical practice or a tool for marketing? When to use antihistamines, intranasal corticosteroids, intranasal anticholinergics, and antileukotrienes for nasal symptoms is debated by specialists and general practitioners. General guidelines have been provided by the Joint Task Force on Practice Parameters in Allergy, Asthma, and Immunology.1 The parameters are not specific, and the management of each patient should be individualized, based on the totality of the patient’s symptoms and severity. Cost-effectiveness along with step-up and step-down approaches should also be used for each patient. Realistically, it seems that for most physicians (nonspecialists), treatment decisions for rhinitis medication use are related to Food and Drug Administration indications, formulary restrictions, and subsequent marketing. Approval of specific drug indications depends on appropriate research protocols that confirm the hypothesis chosen for the study, eg, safety or efficacy. Once the indication is approved, aggressive marketing is used to influence the use of the medication. In the past, marketing was primarily aimed at the prescribing physician, but an ever-increasing use of direct-to-consumer advertising is taking place, in print and in audiovisual media.2,3 How much of the research and marketing is truly for the good of the patient as opposed to a tool for pharmaceutical sales? The article by Pitsios et al4 in this issue of the Annals provides information for consideration regarding the ultimate intent of the study and the resultant effect that may be expected on prescribing patterns. The efficacy and safety of the newer intranasal corticosteroid preparations has been well documented in the literature since the mid-1990s.5–7 Multiple well-designed research studies8 –11 have looked at preseasonal and seasonal control of seasonal (and perennial) allergic rhinitis symptoms. Intranasal corticosteroid preparations have been shown to act very quickly, to be localized in effect, and to have a much greater efficacy than second-generation antihistamines.5 The study by Pitsios et al4 confirms previous success in using intranasal corticosteroids to control seasonal allergic rhinitis (SAR) symptoms. The study uses nedocromil sodium as the comparator for the study. This molecule has been available for study since the late 1980s and is available for pulmonary and ocular use in the United States but has never been released for intranasal use.12 Nedocromil sodium has been successful in managing ongoing SAR symptoms, with an onset of effect within 2 hours of administration.13 As a chromone, it has also demonstrated a preventive or prophylactic effect. The effect of nedocromil sodium compared with mometasone furoate in the study by Pitsios et al4 was as expected. No control group
638
was available to compare the exact level of response between the 2 study drugs. Marketing for the preseasonal use of intranasal corticosteroids and antihistamines is now being peformed in the United States. In view of the known rapid onset and efficacy of intranasal corticosteroids and antihistamines, is it appropriate to consider prophylactic preseasonal administration of these agents with continuation of treatment throughout the season? As previously noted, the practice parameters from the Joint Task Force do not give specific guidance regarding the timing and coordination of intranasal corticosteroid and antihistamine use in the patient with allergic rhinitis.1 In contrast, the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines use the same nomenclature as that being used for asthma since inception of the National Asthma Education and Prevention Program standards.14 –17 This nomenclature includes classification of the rhinitis presentation as “intermittent” or “persistent.” These terms are consistent with the association of underlying pathogenesis and the desired medication effect. The ARIA guidelines suggest the initial use of second-generation antihistamines, with the use of intranasal corticosteroids reserved for more frequent symptoms (⬎4 d/wk). The antihistamine class can be considered the acute reliever medication (similar to 2-agonists), and the intranasal corticosteroid class becomes the controller/preventive (anti-inflammatory) medication. When control is achieved, the medications can be reduced to the lowest dose that will maintain adequate control. It is interesting that the study by Pitsios et al4 of preseasonal treatment of SAR was completed in the European Academy of Allergology and Clinical Immunology theater, where rhinitis management is based on the proven effectiveness of the ARIA guidelines. One of the major considerations for the treatment of allergic rhinitis is the direct cost of medications and the indirect cost of quality-of-life issues.18 As practitioners, our responsibility is to balance these aspects to the best of our ability. The least expensive intranasal corticosteroid has been shown to cost $1.54 per day, as determined by health care management records.19,20 Because this figure is now several years old, the current cost is certainly higher. Here lies the conundrum: is it appropriate to recommend preseasonal use of intranasal corticosteroids and antihistamines when these agents have been shown to have a rapid onset of effect and excellent control of symptoms (in season) when not used in a preseasonal manner? There is no doubt that information in the study by Pitsios et al4 can be used for marketing directly to the patient and to the prescribing physician. Direct-to-consumer marketing is
ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY
being extensively used by pharmaceutical companies to influence patient perception of available medications for specific disease entities.21–23 Allergic rhinitis is one of the major audiovisual disease entities that has been selected for patient promotion. This same information will be provided to nonspecialist prescribing physicians, who do not have the knowledge of current literature and the appropriate available options for medication use. As allergy specialists and patient advocates, do we have the responsibility to our patients to critically review a study and determine whether the hypothesis will result in good clinical practice or use as a marketing tool? JAMES R. CLAFLIN, MD Oklahoma Allergy and Asthma Clinic Oklahoma City, Oklahoma REFERENCES 1. Dykewicz MS, Fineman S, Skoner DP, et al. Diagnosis and management of rhinitis: complete guidelines of the Joint Task Force on Practice Parameters in Allergy, Asthma, and Immunology. Ann Allergy Asthma Immunol. 1998;81:478 –518. 2. Brownfield ED, Bernhardt JM. Direct-to-consumer drug advertisements on network television: an exploration of quantity, frequency, and placement. J Health Commun. 2004;9:561–562. 3. Deshpande A, Menon A. Direct-to-consumer advertising and its utility in health care decision making: a consumer perspective. J Health Commun. 2004:9:499 –513. 4. Pitsios C, Papadopoulos D, Kompoti E, et al. Efficacy and safety of mometasone furoate vs nedocromil sodium as prophylactic treatment for moderate/severe seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 2006;96:671– 676. 5. Nielsen LP, Dahl R. Comparison of intranasal corticosteroids and antihistamines in allergic rhinitis: a review of randomized, controlled trials. Am J Respir Med. 2003;2:55– 65. 6. Transgrud AJ, Whitaker AL. Intranasal corticosteroids for allergic rhinitis. Pharmacotherapy. 2002;22:1458 –1467. 7. Lumry W. A review of the preclinical and clinical data of newer intranasal steroids used in the treatment of allergic rhinitis. J Allergy Clin Immunol. 1999;104(pt 1):S150 –S158. 8. van Drunen C, Meltzer EO. Nasal allergies and beyond: a clinical review of the pharmacology, efficacy, and safety of mometasone furoate. Allergy. 2005;60(suppl 80):5–19.
VOLUME 96, MAY, 2006
9. Onrust SV, Lamb HM. Mometasone furoate: a review of its intranasal use in allergic rhinitis. Drugs. 1998;56:725–745. 10. Munk ZM, Gross GN. Preseasonal, once daily triamcinolone acetonide nasal aerosol for seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 1997;78:325–331. 11. Graft D, Aaronson D. A placebo- and active-controlled randomized trial of prophylactic treatment of seasonal allergic rhinitis with mometasone furoate aqueous nasal spray. J Allergy Clin Immunol. 1996;98:724 –731. 12. Sipila P, Sorri M. Double-blind comparison of nedocromil sodium (1% nasal spray) and placebo in rhinitis caused by birch pollen. Clin Otolaryngol Allied Sci. 1987;12:365–370. 13. Donnelly A, Casale TB. Nedocromil sodium is rapidly effective in the therapy of seasonal allergic rhinitis. J Allergy Clin Immunol. 1993;91:997–1004. 14. Bachert C, van Cauwenberge P. The WHO ARIA (Allergic Rhinitis and its Impact on Asthma) initiative. Chem Immunol Allergy. 2003;82:119 –126. 15. Demoly P, Allaert FA. Validation of the classification of ARIA (Allergic Rhinitis and its Impact on Asthma). Allergy. 2003;58: 672– 675. 16. Storms WW. Rethinking our approach to allergic rhinitis management. Ann Allergy Asthma Immunol. 2002;88(suppl 1): 30 –35. 17. Bousquet F, Lund VJ. Implementation of guidelines for seasonal allergic rhinitis: a randomized controlled trial. Allergy. 2003;58:733–741. 18. Dupclay L Jr, Doyle J. Assessment of intranasal corticosteroid use in allergic rhinitis: benefits, costs, and patient preferences. Am J Manag Care. 2002;8(suppl):S335–S340. 19. Reissman D, Price T, Leibman SW. Cost efficiency of intranasal corticosteroid prescribing patterns in the management of allergic rhinitis. J Manag Care Pharm. 2004;10(suppl):S9 –S13. 20. Hadley JA, Cost-effective pharmacotherapy for inhalant allergic rhinitis. Otolaryngol Clin North Am. 2003;36:825– 836. 21. Kaphingst KA, Dejong W. A content analysis of direct-toconsumer television prescription drug advertisements. J Health Commun. 2004;9:515–528. 22. Chao BA. Evaluating the educational content of direct-toconsumer fulfillment materials. Am J Health Syst Pharm. 2005; 62:620 – 625. 23. Gilbody S, Wilson P. Benefits and harms of direct-to-consumer advertising: a systematic review. Qual Saf Health Care. 2005; 14:246 –250.
639
Good clinical practice or a tool for marketing? When to use antihistamines, intranasal corticosteroids, intranasal anticholinergics, and antileukotrienes for nasal symptoms is debated by specialists and general practitioners. General guidelines have been provided by the Joint Task Force on Practice Parameters in Allergy, Asthma, and Immunology.1 The parameters are not specific, and the management of each patient should be individualized, based on the totality of the patient’s symptoms and severity. Cost-effectiveness along with step-up and step-down approaches should also be used for each patient. Realistically, it seems that for most physicians (nonspecialists), treatment decisions for rhinitis medication use are related to Food and Drug Administration indications, formulary restrictions, and subsequent marketing. Approval of specific drug indications depends on appropriate research protocols that confirm the hypothesis chosen for the study, eg, safety or efficacy. Once the indication is approved, aggressive marketing is used to influence the use of the medication. In the past, marketing was primarily aimed at the prescribing physician, but an ever-increasing use of direct-to-consumer advertising is taking place, in print and in audiovisual media.2,3 How much of the research and marketing is truly for the good of the patient as opposed to a tool for pharmaceutical sales? The article by Pitsios et al4 in this issue of the Annals provides information for consideration regarding the ultimate intent of the study and the resultant effect that may be expected on prescribing patterns. The efficacy and safety of the newer intranasal corticosteroid preparations has been well documented in the literature since the mid-1990s.5–7 Multiple well-designed research studies8 –11 have looked at preseasonal and seasonal control of seasonal (and perennial) allergic rhinitis symptoms. Intranasal corticosteroid preparations have been shown to act very quickly, to be localized in effect, and to have a much greater efficacy than second-generation antihistamines.5 The study by Pitsios et al4 confirms previous success in using intranasal corticosteroids to control seasonal allergic rhinitis (SAR) symptoms. The study uses nedocromil sodium as the comparator for the study. This molecule has been available for study since the late 1980s and is available for pulmonary and ocular use in the United States but has never been released for intranasal use.12 Nedocromil sodium has been successful in managing ongoing SAR symptoms, with an onset of effect within 2 hours of administration.13 As a chromone, it has also demonstrated a preventive or prophylactic effect. The effect of nedocromil sodium compared with mometasone furoate in the study by Pitsios et al4 was as expected. No control group
638
was available to compare the exact level of response between the 2 study drugs. Marketing for the preseasonal use of intranasal corticosteroids and antihistamines is now being peformed in the United States. In view of the known rapid onset and efficacy of intranasal corticosteroids and antihistamines, is it appropriate to consider prophylactic preseasonal administration of these agents with continuation of treatment throughout the season? As previously noted, the practice parameters from the Joint Task Force do not give specific guidance regarding the timing and coordination of intranasal corticosteroid and antihistamine use in the patient with allergic rhinitis.1 In contrast, the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines use the same nomenclature as that being used for asthma since inception of the National Asthma Education and Prevention Program standards.14 –17 This nomenclature includes classification of the rhinitis presentation as “intermittent” or “persistent.” These terms are consistent with the association of underlying pathogenesis and the desired medication effect. The ARIA guidelines suggest the initial use of second-generation antihistamines, with the use of intranasal corticosteroids reserved for more frequent symptoms (⬎4 d/wk). The antihistamine class can be considered the acute reliever medication (similar to 2-agonists), and the intranasal corticosteroid class becomes the controller/preventive (anti-inflammatory) medication. When control is achieved, the medications can be reduced to the lowest dose that will maintain adequate control. It is interesting that the study by Pitsios et al4 of preseasonal treatment of SAR was completed in the European Academy of Allergology and Clinical Immunology theater, where rhinitis management is based on the proven effectiveness of the ARIA guidelines. One of the major considerations for the treatment of allergic rhinitis is the direct cost of medications and the indirect cost of quality-of-life issues.18 As practitioners, our responsibility is to balance these aspects to the best of our ability. The least expensive intranasal corticosteroid has been shown to cost $1.54 per day, as determined by health care management records.19,20 Because this figure is now several years old, the current cost is certainly higher. Here lies the conundrum: is it appropriate to recommend preseasonal use of intranasal corticosteroids and antihistamines when these agents have been shown to have a rapid onset of effect and excellent control of symptoms (in season) when not used in a preseasonal manner? There is no doubt that information in the study by Pitsios et al4 can be used for marketing directly to the patient and to the prescribing physician. Direct-to-consumer marketing is
ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY
being extensively used by pharmaceutical companies to influence patient perception of available medications for specific disease entities.21–23 Allergic rhinitis is one of the major audiovisual disease entities that has been selected for patient promotion. This same information will be provided to nonspecialist prescribing physicians, who do not have the knowledge of current literature and the appropriate available options for medication use. As allergy specialists and patient advocates, do we have the responsibility to our patients to critically review a study and determine whether the hypothesis will result in good clinical practice or use as a marketing tool? JAMES R. CLAFLIN, MD Oklahoma Allergy and Asthma Clinic Oklahoma City, Oklahoma REFERENCES 1. Dykewicz MS, Fineman S, Skoner DP, et al. Diagnosis and management of rhinitis: complete guidelines of the Joint Task Force on Practice Parameters in Allergy, Asthma, and Immunology. Ann Allergy Asthma Immunol. 1998;81:478 –518. 2. Brownfield ED, Bernhardt JM. Direct-to-consumer drug advertisements on network television: an exploration of quantity, frequency, and placement. J Health Commun. 2004;9:561–562. 3. Deshpande A, Menon A. Direct-to-consumer advertising and its utility in health care decision making: a consumer perspective. J Health Commun. 2004:9:499 –513. 4. Pitsios C, Papadopoulos D, Kompoti E, et al. Efficacy and safety of mometasone furoate vs nedocromil sodium as prophylactic treatment for moderate/severe seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 2006;96:671– 676. 5. Nielsen LP, Dahl R. Comparison of intranasal corticosteroids and antihistamines in allergic rhinitis: a review of randomized, controlled trials. Am J Respir Med. 2003;2:55– 65. 6. Transgrud AJ, Whitaker AL. Intranasal corticosteroids for allergic rhinitis. Pharmacotherapy. 2002;22:1458 –1467. 7. Lumry W. A review of the preclinical and clinical data of newer intranasal steroids used in the treatment of allergic rhinitis. J Allergy Clin Immunol. 1999;104(pt 1):S150 –S158. 8. van Drunen C, Meltzer EO. Nasal allergies and beyond: a clinical review of the pharmacology, efficacy, and safety of mometasone furoate. Allergy. 2005;60(suppl 80):5–19.
VOLUME 96, MAY, 2006
9. Onrust SV, Lamb HM. Mometasone furoate: a review of its intranasal use in allergic rhinitis. Drugs. 1998;56:725–745. 10. Munk ZM, Gross GN. Preseasonal, once daily triamcinolone acetonide nasal aerosol for seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 1997;78:325–331. 11. Graft D, Aaronson D. A placebo- and active-controlled randomized trial of prophylactic treatment of seasonal allergic rhinitis with mometasone furoate aqueous nasal spray. J Allergy Clin Immunol. 1996;98:724 –731. 12. Sipila P, Sorri M. Double-blind comparison of nedocromil sodium (1% nasal spray) and placebo in rhinitis caused by birch pollen. Clin Otolaryngol Allied Sci. 1987;12:365–370. 13. Donnelly A, Casale TB. Nedocromil sodium is rapidly effective in the therapy of seasonal allergic rhinitis. J Allergy Clin Immunol. 1993;91:997–1004. 14. Bachert C, van Cauwenberge P. The WHO ARIA (Allergic Rhinitis and its Impact on Asthma) initiative. Chem Immunol Allergy. 2003;82:119 –126. 15. Demoly P, Allaert FA. Validation of the classification of ARIA (Allergic Rhinitis and its Impact on Asthma). Allergy. 2003;58: 672– 675. 16. Storms WW. Rethinking our approach to allergic rhinitis management. Ann Allergy Asthma Immunol. 2002;88(suppl 1): 30 –35. 17. Bousquet F, Lund VJ. Implementation of guidelines for seasonal allergic rhinitis: a randomized controlled trial. Allergy. 2003;58:733–741. 18. Dupclay L Jr, Doyle J. Assessment of intranasal corticosteroid use in allergic rhinitis: benefits, costs, and patient preferences. Am J Manag Care. 2002;8(suppl):S335–S340. 19. Reissman D, Price T, Leibman SW. Cost efficiency of intranasal corticosteroid prescribing patterns in the management of allergic rhinitis. J Manag Care Pharm. 2004;10(suppl):S9 –S13. 20. Hadley JA, Cost-effective pharmacotherapy for inhalant allergic rhinitis. Otolaryngol Clin North Am. 2003;36:825– 836. 21. Kaphingst KA, Dejong W. A content analysis of direct-toconsumer television prescription drug advertisements. J Health Commun. 2004;9:515–528. 22. Chao BA. Evaluating the educational content of direct-toconsumer fulfillment materials. Am J Health Syst Pharm. 2005; 62:620 – 625. 23. Gilbody S, Wilson P. Benefits and harms of direct-to-consumer advertising: a systematic review. Qual Saf Health Care. 2005; 14:246 –250.
639