Oral immunotherapy: Ready for prime time?

Oral immunotherapy: Ready for prime time?

CORRESPONDENCE 289 J ALLERGY CLIN IMMUNOL VOLUME 127, NUMBER 1 3. Schering-Plough. Trial number: P05067. Available at: http://www.clinicalstudyresul...

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3. Schering-Plough. Trial number: P05067. Available at: http://www.clinicalstudyresults. org/documents/company-study_4364_0.pdf. Document dated March 26, 2008. Accessed June 30, 2010. 4. Keith PK, Scadding GK. Are intranasal corticosteroid all equally consistent in managing ocular symptoms of seasonal allergic rhinitis? Curr Med Res Opin 2009;25:2021-41. 5. Antman EM, Ferguson JJ. Should evidence-based proof of efficacy as defined for a specific therapeutic agent be extrapolated to encompass a therapeutic class of agents? Circulation 2003;108:2604-7. 6. Baumann D, Bachert C, H€ogger P. Dissolution in nasal fluid, retention and antiinflammatory activity of fluticasone furoate in human nasal tissue ex vivo. Clin Exp Allergy 2009;39:1540-50. 7. Martin BG, Ratner PH, Hampel FC, Andrews CP, Toler T, Wu W, et al. Optimal dose selection of fluticasone furoate nasal spray for the treatment of seasonal allergic rhinitis in adults and adolescents. Allergy Asthma Proc 2007;28:216-25. 8. Jacobs R, Martin B, Hampel F, Toler W, Ellsworth A, Philpot E. Effectiveness of fluticasone furoate 110 mg once daily in the treatment of nasal and ocular symptoms of seasonal allergic rhinitis in adults and adolescents sensitized to mountain cedar pollen. Curr Med Res Opin 2009;25:1393-401. 9. Fokkens WJ, Jogi R, Reinartz S, Sidorenko I, Sitkauskiene B, Van Oene C, et al. Once daily fluticasone furoate nasal spray is effective in seasonal allergic rhinitis caused by grass pollen. Allergy 2007;62:1078-84. 10. Kaiser HB, Naclerio RM, Given J, Toler TN, Ellsworth EE. Fluticasone furoate nasal spray: a single treatment option for the symptoms of seasonal allergic rhinitis. J Allergy Clin Immunol 2007;119:1430-7. 11. Andrews CP, Martin BG, Jacobs RL, Mohar DE, Diaz JD, Amar NJ, et al. Fluticasone furoate nasal spray is more effective than fexofenadine for nighttime symptoms of seasonal allergy. Allergy Asthma Proc 2009;30:128-38. Available online November 3, 2010. doi:10.1016/j.jaci.2010.08.046

Reply To the Editor: We thank Drs Keith and Lee1 for their interest in our prospective, placebo-controlled study of mometasone furoate nasal spray (MFNS) for the ocular symptoms of seasonal allergic rhinitis (SAR)2 and appreciate their furnishing the data regarding the effects of fluticasone furoate on individual ocular symptoms of SAR. Drs Keith and Lee1 mention the results of a second prospective trial evaluating MFNS for relief of ocular symptoms. While this trial has not been published in a primary article, results from the trial have been available publicly through the clinicalstudyresults.org Web site.3 In addition, results from this study were included in a meta-analysis of the effect of MFNS on ocular symptoms in seasonal allergic rhinitis that was presented at the European Academy of Allergy and Clinical Immunology 2009 meeting4; this analysis is currently being prepared for submission as a full manuscript. Six randomized controlled trials (total N 5 1839) that reported change in total ocular symptom score after treatment with MFNS or placebo were included in the analysis, which showed that MFNS demonstrated significant superiority to placebo in relieving ocular symptoms of tearing, itching, and redness at 15 days and over days 1 to 15. Although Drs Keith and Lee base their comments regarding the ocular efficacy of MFNS solely on the results of the 2 studies they mention, the results of the meta-analysis may provide a more complete picture of the results that can be expected in clinical practice. Drs Keith and Scadding5 have previously noted that in light of the lack of comparative clinical data showing superior efficacy of one intranasal corticosteroid over another, agents may be distinguished on the basis of differences in safety profiles. A review of prescribing information for fluticasone furoate and MFNS suggests that there may be differences in the potential for adverse events between these 2 agents, particularly those associated with ocular corticosteroid exposure. In a 12-month study of 806

adults and adolescents, 12 patients receiving fluticasone furoate experienced intraocular pressure that increased above normal levels, versus none for placebo; 7 patients receiving fluticasone furoate developed cataracts during the study (as assessed by slit lamp examination), versus 1 patient receiving placebo.6 In a 12month safety study of MFNS, none of the 139 patients receiving active treatment developed cataracts as assessed by slit lamp examination, and no significant change from baseline in mean intraocular pressure was noted.7 Though we feel it is reasonable to conclude from the collected evidence that efficacy on ocular symptoms of SAR is an intranasal corticosteroid class effect, variations within the class may exist in efficacy and in safety. Bruce M. Prenner, MDa Bobby Q. Lanier, MDb David I. Bernstein, MDc Tulin Shekar, MSd Ariel Teper, MDd From athe Allergy Associates Medical Group, San Diego, Calif; bthe University of North Texas, North Texas Health Science Center, Fort Worth, Tex; cthe Division of Immunology-Allergy, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio; and dMerck Research Laboratories, Kenilworth, NJ. E-mail: [email protected] aaamg.com. Supported by Merck & Co, formerly Schering Corp. Disclosure of potential conflict of interest: B. Q. Lanier receives research support from Merck, Novartis, Alcon Labs, Genentech, AstraZeneca, and Teva and serves as medical director for ACAAI. D. I. Bernstein has consultant arrangements with Merck and receives research support from Schering-Plough and Merck. T. Shekar and A. Teper are employed by Merck & Co, Inc. B. M. Prenner receives research support from Abbot, Aerovent, Alcon, Amgen, Amphastar, Boehringer Ingelheim, Forrest, Genentech, GlaxoSmithKline, Map Pharmaceuticals, Meda, Novartis, Pharmaxis, Sanofi-Aventis, the Schering-Plough Research Institute, Sepracor, Skyepharma, UCB, and Wyeth; has consultant arrangements with Abbott, Astellas, AstraZeneca, Dynavax, Critical Therapeutics, Genentech, GlaxoSmithKline, King Pharmaceuticals, Meda, Merck, Novartis, Protein Design Labs, Sanofi-Aventis, Schering-Plough, Sciele Pharma, Stallergenes, and Teva; and is on the speakers’ bureau for Altana, Allergan, AstraZeneca, Astellas, Genentech, GlaxoSmithKline, Meda, Merck, Novartis, Sanofi-Aventis, Sepracor, Schering-Plough, and Teva. REFERENCES 1. Keith P, Lee LA. Fluticasone furoate nasal spray is the only intranasal corticosteroid to consistently reduce the ocular symptoms of seasonal allergic rhinitis. J Allergy Clin Immunol 2011;127:288-9. 2. Prenner BM, Lanier BQ, Bernstein DI, Shekar T, Teper A. Mometasone furoate nasal spray reduces the ocular symptoms of seasonal allergic rhinitis. J Allergy Clin Immunol 2010;125:1247-53. 3. Schering-Plough. Trial no. P05067. Available at: http://www.clinicalstudyresults. org/drugdetails/?drug_name_id5150&sort5c.company_name&page52&drug_id5 4364. Accessed June 30, 2010. 4. Bielory L, Canonica G. Mometasone furoate nasal spray significantly reduces individual ocular symptoms in subjects with seasonal allergic rhinitis [Abstract]. Allergy 2009;64(suppl 90):592. 5. Keith PK, Scadding GK. Comment on: Are intranasal corticosteroids all equally consistent in managing ocular symptoms of seasonal allergic rhinitis? Curr Med Res Opin 2010;26:1140. 6. Veramyst [prescribing information]. Research Triangle Park (NC): GlaxoSmithKline; 2009. 7. Nasonex [prescribing information]. Kenilworth (NJ): Schering Corp (now Merck & Co); 2009. Available online November 4, 2010. doi:10.1016/j.jaci.2010.08.045

Oral immunotherapy: Ready for prime time? To the Editor: In the July 2010 issue of the Journal, Thyagarajan et al1 published an editorial titled ‘‘Peanut oral immunotherapy is not

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ready for clinical use.’’ At the end of the article, they extend their conclusion to other foods as well. The authors state that ‘‘the major issue to address is whether the likelihood of patients experiencing accidental food reactions over a given period is more or less than the percentage of patients who cannot tolerate OIT.’’1 We feel that this comparison is not the correct one. Patients who cannot tolerate oral immunotherapy (OIT) were not in any danger of death. In fact, no patient even required hospitalization for adverse reactions as a result of OIT. On the other hand, accidental ingestion of an allergenic food may be fatal.2 These cases are not adequately represented in the medical literature because often these reactions occur outside the hospital. In Israel alone, for example, there were at least 3 fatal cases of milk allergy in the past 5 years. All of these cases involved youngsters who, although aware of their medical condition, were exposed to hidden allergen. The knowledge of these deaths came to our attention through the media, and we gathered the information, not without difficulty, from their caregivers (Levy M et al, manuscript in preparation). The authors also raise some concerns regarding patient selection and dosing under various circumstances. Similar concerns have been raised in the treatment of allergic rhinitis by subcutaneous immunotherapy (SCIT),3 a treatment that was introduced more than a century ago and is one of the cornerstones of therapy for our specialty. In fact, the comparison of SCIT to OIT is quite revealing. Although the benefits of SCIT for airborne allergens are unquestionable, this treatment modality is not lifesaving but rather improves the quality of life. Yet despite the widespread use of SCIT as a treatment modality, the side effects of SCIT are potentially fatal.3 In contrast, more than 15 publications show that OIT increases the threshold of sensitivity to the allergenic food and thus is potentially lifesaving, without significant risk. We agree with the authors that there should be strict guidelines regarding the administration of these treatments to avoid dangerous overuse. Defining these guidelines may reduce the risk and enable a significant proportion of the at-risk population to benefit from this promising treatment. In addition, an adoption of these guidelines will help establish third-party reimbursement for such services, enabling the implementation of such a program. Restricting treatment of patients with food allergy to clinical trials would preclude the benefits from reaching the population at large. We believe that the time for OIT for clinical use has indeed arrived and strongly support the development of guidelines to expand its use and prevent further food allergy–related morbidity and mortality. Yitzhak Katz, MDa,b Michael R. Goldberg, MD, PhDa Miguel Stein, MDa Michael Levy, MDa From athe Allergy and Immunology Institute, Assaf Harofeh Medical Center, Zerifin; and bthe Department of Pediatrics, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. E-mail: [email protected] Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.

REFERENCES 1. Thyagarajan A, Varshney P, Jones SM, Sicherer S, Wood R, Vickery BP, et al. Peanut oral immunotherapy is not ready for clinical use. J Allergy Clin Immunol 2010;126:31-2. 2. Atkins D, Bock SA. Fatal anaphylaxis to foods: epidemiology, recognition and prevention. Curr Allergy Asthma Rep 2009;3:179-85.

3. Frew AJ. Allergen immunotherapy. J Allergy Clin Immunol 2010;125: S306-13. Available online October 30, 2010. doi:10.1016/j.jaci.2010.08.053

Office-based oral immunotherapy for food allergy is safe and effective To the Editor: The editorial by Thyagarajan et al,1 ‘‘Peanut oral immunotherapy is not ready for clinical use,’’ in the July 2010 issue of the Journal argues for limiting oral immunotherapy (OIT) to academic centers. They admonish physicians to ‘‘first, do no harm’’ but then go on to discount the effects of food allergy managed only by avoidance. The authors point out that several important questions remain unanswered and that there is a risk of reactions to OIT as well as the risk of reactions managed with avoidance.2,3 They do not, however, discuss the frequency of near-fatal and fatal reactions caused by accidental exposures and occurring during OIT. To our knowledge, the only death caused by OIT occurred during a formal trial at an academic center and was caused by a dosing error. Many more deaths have resulted from accidental exposure. Comparing the harm caused by OIT to the harm caused by an avoidance strategy cannot ignore the risk of death. The authors do not discuss the psychosocial impact of food allergy on patients and families. Children with peanut allergy reported more impairment of daily activities and social interactions than children with rheumatologic disease4 and greater anxiety about eating reactions than children with diabetes.5 The significant morbidity of food allergy managed by avoidance should not be ignored. Implicit in the editorial is the notion that OIT in an academic setting is inherently more appropriate than when a board-certified allergist/immunologist in an office setting controls the entire experience. On the basis of our experience, representing the completed treatment of more than 175 patients in 3 different locations, we reject this notion. Although controlled trials may answer some of the questions regarding OIT, subcutaneous immunotherapy for aeroallergen sensitivity and coronary artery bypass grafting became part of routine clinical practice and afforded many patients significant clinical benefits before the completion of randomized, controlled trials. These procedures were later subject to controlled investigation that led to important refinements. There is no reason, a priori, that OIT should not be treated the same way. We believe that although OIT is not without risk, it is a potentially life-altering treatment. Fully informed patients and parents should be free to choose the management approach that is best for themselves and their families. Richard L. Wasserman, MD, PhDa Robert W. Sugerman, MDa Nana Mireku-Akomeah, MDa Lyndon Mansfield, MDb James W. Baker, MDc From aDallasAllergyImmunology, Dallas, Tex; bWestern Sky Medical Research, El Paso, Tex; and cBaker Allergy, Asthma, and Dermatology Research Center, Lake Oswego, Ore. E-mail: [email protected]