Multiple-allergen and single-allergen immunotherapy strategies in polysensitized patients: Looking at the published evidence
2012; Elsevier BV; Volume: 129; Issue: 4 Linguagem: Inglês
10.1016/j.jaci.2011.11.019
ISSN1097-6825
AutoresMoisés A. Calderón, Linda Cox, Thomas B. Casale, Philippe Moingeon, Pascal Demoly,
Tópico(s)Dermatology and Skin Diseases
ResumoIn allergen immunotherapy there is debate as to whether polysensitized patients are best treated with many allergens simultaneously (chosen according to the sensitization profile, a predominantly North American approach) or a single allergen (chosen according to the most clinically problematic allergy, a predominantly European approach). In patients seeking treatment for moderate-to-severe respiratory allergies, polysensitization is more prevalent (range, 50% to 80%) than monosensitization in both the United States and Europe. Safe, effective, single-allergen preparations will most likely have been tested in polysensitized patients. In robust, large-scale clinical trials of grass pollen sublingual tablets, polysensitized patients benefited at least as much from allergen immunotherapy as monosensitized patients. A recent review of multiallergen immunotherapy concluded that simultaneous delivery of multiple unrelated allergens can be clinically effective but that there was a need for additional investigation of therapy with more than 2 allergen extracts (particularly in sublingual allergen immunotherapy). More work is also required to determine whether single-allergen and multiallergen immunotherapy protocols elicit distinct immune responses in monosensitized and polysensitized patients. Sublingual and subcutaneous multiallergen immunotherapy in polysensitized patients requires more supporting data to validate its efficacy in practice. In allergen immunotherapy there is debate as to whether polysensitized patients are best treated with many allergens simultaneously (chosen according to the sensitization profile, a predominantly North American approach) or a single allergen (chosen according to the most clinically problematic allergy, a predominantly European approach). In patients seeking treatment for moderate-to-severe respiratory allergies, polysensitization is more prevalent (range, 50% to 80%) than monosensitization in both the United States and Europe. Safe, effective, single-allergen preparations will most likely have been tested in polysensitized patients. In robust, large-scale clinical trials of grass pollen sublingual tablets, polysensitized patients benefited at least as much from allergen immunotherapy as monosensitized patients. A recent review of multiallergen immunotherapy concluded that simultaneous delivery of multiple unrelated allergens can be clinically effective but that there was a need for additional investigation of therapy with more than 2 allergen extracts (particularly in sublingual allergen immunotherapy). More work is also required to determine whether single-allergen and multiallergen immunotherapy protocols elicit distinct immune responses in monosensitized and polysensitized patients. Sublingual and subcutaneous multiallergen immunotherapy in polysensitized patients requires more supporting data to validate its efficacy in practice. In the field of allergen immunotherapy, there is much debate as to whether polysensitized patients are best treated with several allergens (chosen according to the individual's sensitization profile)1Cox L. Nelson H. Lockey R. Calabria C. Chacko T. Finegold I. et al.Allergen immunotherapy: a practice parameter third update.J Allergy Clin Immunol. 2011; 127: S1-S55Abstract Full Text Full Text PDF PubMed Scopus (828) Google Scholar or a single allergen (corresponding to the most clinically problematic allergy).2van Cauwenberge P. Bachert C. Passalacqua G. Bousquet J. Canonica G.W. Durham S.R. et al.Consensus statement on the treatment of allergic rhinitis. European Academy of Allergology and Clinical Immunology.Allergy. 2000; 55: 116-134Crossref PubMed Scopus (605) Google Scholar We looked at the evidence for the efficacy and safety of these 2 approaches in polysensitized patients. We consider here that single-allergen immunotherapy includes the use of extracts containing several closely related allergens (eg, a 5-grass-pollen extract). Conversely, we consider that multiallergen immunotherapy refers to mixtures with little or no cross-reactivity (eg, grass pollen, tree pollen, weed pollen, house dust mite [HDM], and animal dander).Polysensitization is more prevalent than monosensitizationData from 11,355 participants in the first European Community Respiratory Health Survey (median age, 34 years) tested with a panel of 4 to 9 skin prick tests, 4 to 5 serum allergen-specific IgE measurements, or both showed that, depending on the center and the test methods, 57.0% to 67.8% of European populations were not sensitized to any of the test allergens, 16.2% to 19.6% were monosensitized, and 12.8% to 25.3% were polysensitized.3Bousquet P.J. Castelli C. Daures J.P. Heinrich J. Hooper R. Sunyer J. et al.Assessment of allergen sensitization in a general population-based survey (European Community Respiratory Health Survey I).Ann Epidemiol. 2010; 20: 797-803Abstract Full Text Full Text PDF PubMed Scopus (57) Google ScholarSkin sensitization to common indoor and outdoor allergens in the US general population aged 6 to 59 years was investigated in the second and third National Health and Nutrition Examination Surveys (NHANES II [1976-1980] and NHANES III [1988-1994]). In NHANES III 10,863 patients participated in skin testing: 45.7% were not sensitized to any of the test allergens, 15.5% were monosensitized, and 38.8% were polysensitized.4Arbes Jr., S.J. Gergen P.J. Elliott L. Zeldin D.C. Prevalences of positive skin test responses to 10 common allergens in the US population: results from the third National Health and Nutrition Examination Survey.J Allergy Clin Immunol. 2005; 116: 377-383Abstract Full Text Full Text PDF PubMed Scopus (542) Google Scholar Baatenburg de Jong et al5Baatenburg de Jong A. Dikkeschei L.D. Brand P.L. Sensitization patterns to food and inhalant allergens in childhood: a comparison of non-sensitized, monosensitized, and polysensitized children.Pediatr Allergy Immunol. 2011; 22: 166-171Crossref PubMed Scopus (87) Google Scholar tested allergen sensitization in 9044 children referred to a regional clinical laboratory in The Netherlands: 60.1% were found not to be sensitized to any of the 13 food and inhalant allergens tested, 12.4% were monosensitized, 18.9% were sensitized to 2 to 4 allergens, and 8.6% were sensitized to 5 or more allergens. Hence polysensitization is more prevalent than monosensitization in the general population.Polysensitization is much more prevalent in patients consulting allergists. In the French Odissee study, 62% of 4227 patients registered by 264 physicians were polysensitized.6Didier A. Chartier A. Demonet G. [Specific sublingual immunotherapy: for which profiles of patients in practice? Midterm analysis of ODISSEE (observatory of the indication and management of respiratory allergies [rhinitis and/or conjunctivitis and/or allergic asthma] by specific sublingual immunotherapy)].Rev Fr Allergol. 2010; 50: 426-433Crossref Scopus (21) Google Scholar In a US study of 1338 patients with objectively diagnosed mild-to-moderate asthma, Craig et al7Craig T.J. King T.S. Lemanske Jr., R.F. Wechsler M.E. Icitovic N. Zimmerman Jr., R.R. et al.Aeroallergen sensitization correlates with PC(20) and exhaled nitric oxide in subjects with mild-to-moderate asthma.J Allergy Clin Immunol. 2008; 121: 671-677Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar reported that only 5% were not sensitized and that 81% of the sensitized patients reacted to 3 or more allergens. The use of component-based diagnostic tests with purified natural or recombinant allergens has revealed that a significant minority of polysensitized patients have IgE against highly cross-reactive panallergens (ranging from 10% for calcium-binding proteins to around 40% for profilin).8Mari A. Scala E. Allergenic extracts for specific immunotherapy: to mix or not to mix?.Int Arch Allergy Immunol. 2006; 141: 57-60Crossref PubMed Scopus (10) Google Scholar Similarly, the majority of participants in recent allergen immunotherapy clinical trials were polysensitized.9Malling H.J. Montagut A. Melac M. Patriarca G. Panzner P. Seberova E. et al.Efficacy and safety of 5-grass pollen sublingual immunotherapy tablets in patients with different clinical profiles of allergic rhinoconjunctivitis.Clin Exp Allergy. 2009; 39: 387-393Crossref PubMed Scopus (96) Google Scholar, 10Emminger W. Durham S.R. Riis B. Maloney J. Nolte H. The efficacy of single-grass-allergen-immunotherapy-tablet treatment in mono- and multi-sensitized allergic rhinitis patients: findings from a post hoc analysis.J Allergy Clin Immunol. 2009; 123: S75Abstract Full Text Full Text PDF Google ScholarStrategies for allergen immunotherapy in polysensitized patientsMeta-analyses of double-blind, placebo-controlled (DBPC) trials and recent, large, well-designed, well-powered studies using standardized allergen preparations have generated high levels of evidence in favor of the efficacy of allergen immunotherapy.11Calderón M. Mösges R. Hellmich M. Demoly P. Towards evidence-based medicine in specific grass pollen immunotherapy.Allergy. 2010; 65: 420-434Crossref PubMed Scopus (30) Google Scholar However, the European and US practice guidelines for subcutaneous allergen immunotherapy (SCIT) differ significantly. In Europe most formulations are single-allergen extracts, whereas preparations in the United States contain an average of 8 different components.12Cox L. Jacobsen L. Comparison of allergen immunotherapy practice patterns in the United States and Europe.Ann Allergy Asthma Immunol. 2009; 103: 451-459Abstract Full Text Full Text PDF PubMed Scopus (151) Google Scholar The prevailing view in Europe is that (1) a polysensitized patient is not necessarily polyallergic and (2) depending on the seasonality of multiple allergen exposure, multiple allergies do not always constitute a clinical problem. The most troublesome allergy is then treated with a single-allergen preparation.2van Cauwenberge P. Bachert C. Passalacqua G. Bousquet J. Canonica G.W. Durham S.R. et al.Consensus statement on the treatment of allergic rhinitis. European Academy of Allergology and Clinical Immunology.Allergy. 2000; 55: 116-134Crossref PubMed Scopus (605) Google Scholar The predominant view in the United States is that there is an advantage in treating as many of the patient's actual or potential sensitizations/allergies as possible.1Cox L. Nelson H. Lockey R. Calabria C. Chacko T. Finegold I. et al.Allergen immunotherapy: a practice parameter third update.J Allergy Clin Immunol. 2011; 127: S1-S55Abstract Full Text Full Text PDF PubMed Scopus (828) Google Scholar American allergists prefer to include all relevant allergens because of the concern over the significant time investment needed in SCIT, especially during the build-up phase. If a patient with both seasonal grass and weed symptoms and perennial cat-induced symptoms is only treated for one of these 3 allergens after a lengthy build-up schedule, the allergist might have difficulties explaining the use of this strategy if exposure to the 2 untreated allergens provokes troublesome symptoms. In this situation standard US practice is to treat all relevant allergens.Single-allergen sublingual allergen immunotherapy in monosensitized versus polysensitized patientsEfficacyGiven that only a small proportion of allergic patients are monosensitized, most clinical trials of allergen immunotherapy will have been performed in polysensitized participants (unless monosensitization is an inclusion criterion). Most such trials include a sensitization screening panel of single-allergen extracts. Malling et al9Malling H.J. Montagut A. Melac M. Patriarca G. Panzner P. Seberova E. et al.Efficacy and safety of 5-grass pollen sublingual immunotherapy tablets in patients with different clinical profiles of allergic rhinoconjunctivitis.Clin Exp Allergy. 2009; 39: 387-393Crossref PubMed Scopus (96) Google Scholar performed a post hoc analysis of a recent multinational, well-powered, DBPC clinical trial of a once-daily 5-grass-pollen sublingual tablet formulation (Table I).13Didier A. Malling H.J. Worm M. Horak F. Jäger S. Montagut A. et al.Optimal dose, efficacy, and safety of once-daily sublingual immunotherapy with a 5-grass pollen tablet for seasonal allergic rhinitis.J Allergy Clin Immunol. 2007; 120: 1338-1345Abstract Full Text Full Text PDF PubMed Scopus (439) Google Scholar The Average Rhinoconjunctivitis Total Symptom Score during the pollen season in the placebo group and 2 treatment groups did not differ significantly according to sensitization status. Malling et al9Malling H.J. Montagut A. Melac M. Patriarca G. Panzner P. Seberova E. et al.Efficacy and safety of 5-grass pollen sublingual immunotherapy tablets in patients with different clinical profiles of allergic rhinoconjunctivitis.Clin Exp Allergy. 2009; 39: 387-393Crossref PubMed Scopus (96) Google Scholar concluded that sensitization status was not a significant baseline covariate and that "the risk-benefit ratio validates the use of 300 IR [five-grass pollen] tablets in clinical practice in all of these patient subgroups, regardless of … sensitization status." However, the trial in question featured a somewhat narrow definition of polysensitization/polyallergy; patients sensitized to allergens other than grass pollen were included in the study only if the said allergens did not induce potentially confounding symptoms during the grass pollen season. Hence a common clinical situation for which multiallergen immunotherapy is often considered (ie, ≥1 seasonal allergies with a concomitant allergy to ≥1 perennial allergens, such as animal dander or HDM) was not taken into account by the latter study.Table ISummary of 2 large-scale DBPC clinical trials of single-allergen grass pollen sublingual tablet formulations in polysensitized and monosensitized patients with allergic rhinoconjunctivitisMalling et al9Malling H.J. Montagut A. Melac M. Patriarca G. Panzner P. Seberova E. et al.Efficacy and safety of 5-grass pollen sublingual immunotherapy tablets in patients with different clinical profiles of allergic rhinoconjunctivitis.Clin Exp Allergy. 2009; 39: 387-393Crossref PubMed Scopus (96) Google ScholarEmminger et al10Emminger W. Durham S.R. Riis B. Maloney J. Nolte H. The efficacy of single-grass-allergen-immunotherapy-tablet treatment in mono- and multi-sensitized allergic rhinitis patients: findings from a post hoc analysis.J Allergy Clin Immunol. 2009; 123: S75Abstract Full Text Full Text PDF Google ScholarStudy description and populationPost hoc analysis of a DBPC clinical study of a total of 628 adults with moderate-to-severe grass pollen–induced allergic rhinoconjunctivitisPost hoc analysis of year 1 of a 3-year DBPC clinical study of a total of 568 adults with grass pollen–induced allergic rhinoconjunctivitisSLIT formulationOnce-daily sublingual tablets containing extracts of 5 related grass pollens at doses of 100, 300, or 500 IR or placeboOnce-daily sublingual tablets containing Phleum pratense pollen extract) at a dose of 75,000 SQ-T/2,800 bioequivalent allergen units or placeboSLIT regimenOnce daily, with 4 months of preseasonal treatment and then coseasonal treatmentOnce daily, with 4 months of preseasonal treatment and then coseasonal treatmentEfficacy end pointARTSSARTSS plus 2 additional ocular symptoms (eye redness and grittiness)Sensitization groupsMonosensitization vs polysensitization (>51.5% of the participants were polysensitized)Monosensitization to grass pollen (28%); polysensitization to grass pollen and tree pollen (and possibly other allergens [37%]); polysensitization to grass pollen and ≥1 other allergens (but not tree pollen [35%])Efficacy resultsPlacebo group (ARTSS)Overall: 4.93 ± 3.23Monosensitized: 4.59 ± 3.06Polysensitized: 5.18 ± 3.34300-IR group (ARTSS)Overall: 3.58 ± 2.98Monosensitized: 3.93 ± 3.01Polysensitized: 3.25 ± 2.93500-IR groupOverall: 3.74 ± 3.14Monosensitized: 3.74 ± 2.90Polysensitized: 3.74 ± 3.35No direct monosensitization vs polysensitization comparison but significantly lower (P < .0001) median symptom scores (by 31%, 44%, and 30% for the treated monosensitized, polysensitized grass plus tree, and polysensitized grass plus other patients, respectively) and medication scores (by 49%, 27% and 60%, respectively) than for placeboSafety profileSimilar safety profiles across all sensitivity/sensitization subgroupsNot reportedARTSS, Average Rhinoconjunctivitis Total Symptom Score; IR, index of reactivity. Open table in a new tab The results of a similar post hoc analysis of the first year of a 3-year DBPC trial14Durham S.R. Yang W.H. Pedersen M.R. Johansen N. Rak S. Sublingual immunotherapy with once-daily grass allergen tablets: a randomized controlled trial in seasonal allergic rhinoconjunctivitis.J Allergy Clin Immunol. 2006; 117: 802-809Abstract Full Text Full Text PDF PubMed Scopus (481) Google Scholar evaluating the efficacy of sublingual allergen immunotherapy (SLIT) with a once-daily Phleum pratense tablet were reported in abstract format by Emminger et al.10Emminger W. Durham S.R. Riis B. Maloney J. Nolte H. The efficacy of single-grass-allergen-immunotherapy-tablet treatment in mono- and multi-sensitized allergic rhinitis patients: findings from a post hoc analysis.J Allergy Clin Immunol. 2009; 123: S75Abstract Full Text Full Text PDF Google Scholar Three sensitization groups were constituted (Table I): grass pollen monosensitization, polysensitization to grass pollen and tree pollen (and possibly other allergens), and polysensitization to grass pollen and at least 1 other allergen (but not tree pollen). A narrow definition of polysensitization/polyallergy was again applied: patients with confounding allergies were not included. Compared with the placebo group, all 3 sensitization groups had significantly lower median daily symptom (all P < .0001) and medication (all P < .0001) scores (Table I). Indeed, the tree-polysensitized group showed the greatest reduction in median daily symptoms, and the non–tree-polysensitized group showed the greatest reduction in median daily medication scores, although the statistical significance of these differences was not tested. Hence single-allergen SLIT was again found to be clinically effective in both polysensitized and monosensitized patients.Ciprandi et al15Ciprandi G. Cadario G. Di Gioacchino M. Gangemi S. Minelli M. Ridolo E. et al.Sublingual immunotherapy in polysensitized allergic patients with rhinitis and/or asthma: allergist choices and treatment efficacy.J Biol Regul Homeost Agents. 2009; 23: 165-171PubMed Google Scholar, 16Ciprandi G. Cadario G. Valle C. Ridolo E. Verini M. Di Gioacchino M. et al.Sublingual immunotherapy in polysensitized patients: effect on quality of life.J Investig Allergol Clin Immunol. 2010; 20: 274-279PubMed Google Scholar, 17Ciprandi G. Incorvaia C. Puccinelli P. Scurati S. Masieri S. Frati F. The POLISMAIL lesson: sublingual immunotherapy may be prescribed also in polysensitized patients.Int J Immunopathol Pharmacol. 2010; 23: 637-640PubMed Google Scholar have published several reports on the use of primarily single-allergen SLIT in polysensitized adults and children. In a prospective, open, observational study, 165 polysensitized adult patients with confirmed allergic rhinitis, asthma, or both (Global Initiative for Asthma criteria) received 1 year of SLIT with a single extract, and 65 received a mixture of 2 extracts.15Ciprandi G. Cadario G. Di Gioacchino M. Gangemi S. Minelli M. Ridolo E. et al.Sublingual immunotherapy in polysensitized allergic patients with rhinitis and/or asthma: allergist choices and treatment efficacy.J Biol Regul Homeost Agents. 2009; 23: 165-171PubMed Google Scholar The mean number of skin sensitizations per patient was 3.65, with the most common being grasses (81.6%), Parietaria species (48.4%), and Dermatophagoides species (46.7%). The significant decrease in symptom and medication scores for the study population as a whole and the lack of systemic reactions after 1 year of treatment in both groups prompted the authors to conclude that single-allergen SLIT (administered to 71% of the patients) was safe and effective in polysensitized patients. Efficacy results for the groups of patients treated with single and multiple allergens were not reported separately. A further report on a similar cohort of 167 polysensitized patients treated primarily (73.6%) with a sublingual single-allergen extract (grass or HDM) stated that the mean score on the Rhinoconjunctivitis Quality of Life Questionnaire improved from 3.96 at baseline to 2.89 after 1 year of allergen immunotherapy relative to placebo (P < .01: a 1-point reduction is considered clinically relevant).16Ciprandi G. Cadario G. Valle C. Ridolo E. Verini M. Di Gioacchino M. et al.Sublingual immunotherapy in polysensitized patients: effect on quality of life.J Investig Allergol Clin Immunol. 2010; 20: 274-279PubMed Google Scholar Likewise, a significant improvement in quality of life was observed after 2 years of SLIT in 87 patients (two thirds of whom received a single allergen extract).17Ciprandi G. Incorvaia C. Puccinelli P. Scurati S. Masieri S. Frati F. The POLISMAIL lesson: sublingual immunotherapy may be prescribed also in polysensitized patients.Int J Immunopathol Pharmacol. 2010; 23: 637-640PubMed Google Scholar However, the open design and the lack of a control group decreased the level of evidence provided by this work.SafetyIn the study analyzed by Malling et al,9Malling H.J. Montagut A. Melac M. Patriarca G. Panzner P. Seberova E. et al.Efficacy and safety of 5-grass pollen sublingual immunotherapy tablets in patients with different clinical profiles of allergic rhinoconjunctivitis.Clin Exp Allergy. 2009; 39: 387-393Crossref PubMed Scopus (96) Google Scholar most of the adverse reactions to active treatment were local (eg, oral pruritus or throat irritation) and mild to moderate in severity and resolved spontaneously without further action.13Didier A. Malling H.J. Worm M. Horak F. Jäger S. Montagut A. et al.Optimal dose, efficacy, and safety of once-daily sublingual immunotherapy with a 5-grass pollen tablet for seasonal allergic rhinitis.J Allergy Clin Immunol. 2007; 120: 1338-1345Abstract Full Text Full Text PDF PubMed Scopus (439) Google Scholar There were no obvious safety profile differences between polysensitized and monosensitized participants.9Malling H.J. Montagut A. Melac M. Patriarca G. Panzner P. Seberova E. et al.Efficacy and safety of 5-grass pollen sublingual immunotherapy tablets in patients with different clinical profiles of allergic rhinoconjunctivitis.Clin Exp Allergy. 2009; 39: 387-393Crossref PubMed Scopus (96) Google Scholar Ciprandi et al15Ciprandi G. Cadario G. Di Gioacchino M. Gangemi S. Minelli M. Ridolo E. et al.Sublingual immunotherapy in polysensitized allergic patients with rhinitis and/or asthma: allergist choices and treatment efficacy.J Biol Regul Homeost Agents. 2009; 23: 165-171PubMed Google Scholar did not observe any systemic reactions and concluded that predominantly single-allergen SLIT was safe in both polysensitized and monosensitized patients.Single-allergen SCIT in monosensitized versus polysensitized patientsTo the best of our knowledge, no single-allergen SCIT trials have been specifically designed to compare efficacy in monosensitized and polysensitized patients. However, a recent, large-scale, DBPC randomized controlled trial demonstrating the safety and efficacy of single-allergen SCIT featured a high proportion of polysensitized patients (77%).18Frew A.J. Powell R.J. Corrigan C.J. Durham S.R. Efficacy and safety of specific immunotherapy with SQ allergen extract in treatment-resistant seasonal allergic rhinoconjunctivitis.J Allergy Clin Immunol. 2006; 117: 319-325Abstract Full Text Full Text PDF PubMed Scopus (336) Google Scholar There were no significant differences between the polysensitized and monosensitized subgroups in terms of symptom score, medication score, quality of life, and overall satisfaction.Multiallergen immunotherapyDespite the widespread use of multiallergen immunotherapy, a recent review has highlighted the low level of evidence for the efficacy and safety of this approach (whether for SCIT or SLIT). A comprehensive search of the English-language and non–English-language literature on multiallergen immunotherapy for patients with allergic rhinitis and asthma published between 1961 and 2007 by Nelson19Nelson H.S. Multiallergen immunotherapy for allergic rhinitis and asthma.J Allergy Clin Immunol. 2009; 123: 763-769Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar identified 13 studies in which 2 or more unrelated allergens were simultaneously administered. Few were well-designed, well-powered DBPC trials. Head-to-head comparative data with single-allergen regimens were rarely provided. Population sizes ranged from 24 to 208. Nelson concluded that simultaneous delivery of multiple unrelated allergens can be clinically effective but that there was a need for additional investigation of therapy with more than 2 allergen extracts (particularly in SLIT).Of course, the investigation of multiallergen immunotherapy in monosensitized patients is discouraged for ethical reasons. Hence most head-to-head studies have compared single-allergen immunotherapy in monosensitized patients with multiallergen immunotherapy in polysensitized patients. Some multiallergen mixtures also face formulation problems (at least with respect to the regulatory situation in Europe) because correct dosage and pharmaceutical stability can be hard to achieve, with a documented risk of proteolytic degradation of allergens in mixtures containing cockroach or mold extracts.20Nelson H.S. Iklé D. Buchmeier A. Studies of allergen extract stability: the effects of dilution and mixing.J Allergy Clin Immunol. 1996; 98: 382-388Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar, 21Plunkett G. Stability of allergen extracts used in skin testing and immunotherapy.Curr Opin Otolaryngol Head Neck Surg. 2008; 16: 285-291Crossref PubMed Scopus (21) Google ScholarMultiallergen SLIT in polysensitized patientsTo examine whether the efficacy of SLIT with a single allergen was reduced by combination with other allergen extracts, Amar et al22Amar S.M. Harbeck R.J. Sills M. Silveira L.J. O'Brien H. Nelson H.S. Response to sublingual immunotherapy with grass pollen extract: monotherapy versus combination in a multiallergen extract.Allergy Clin Immunol. 2009; 124: 150-156Abstract Full Text Full Text PDF Scopus (126) Google Scholar randomized 54 patients to one of three 10-month treatment arms with placebo, single-allergen SLIT (standardized timothy extract administered as drops: 19 μg of Phl p 5 daily) or multiallergen SLIT (the same dose of timothy extract plus 9 additional pollen extracts) and scored symptoms and medication intake during the 2008 grass pollen season in Denver, Colorado. The authors referred to "predominantly polysensitized patients," according to the results of skin prick tests. There were no significant symptom or medication score differences versus placebo in either treatment group. The researchers ascribed this finding to very low grass pollen counts and the small sample size. However, significant posttreatment changes in various immune parameters for the single-allergen group (but not the multiallergen group) prompted Amar et al22Amar S.M. Harbeck R.J. Sills M. Silveira L.J. O'Brien H. Nelson H.S. Response to sublingual immunotherapy with grass pollen extract: monotherapy versus combination in a multiallergen extract.Allergy Clin Immunol. 2009; 124: 150-156Abstract Full Text Full Text PDF Scopus (126) Google Scholar to suggest that the coadministration of multiple allergens interfered with the effectiveness of timothy grass SLIT.Multiallergen SCIT in polysensitized patientsEfficacyBousquet et al23Bousquet J. Becker W.M. Hejjaoui A. Chanal I. Lebel B. Dhivert H. et al.Differences in clinical and immunologic reactivity of patients allergic to grass pollens and to multiple-pollen species. II. Efficacy of a double-blind, placebo-controlled, specific immunotherapy with standardized extracts.J Allergy Clin Immunol. 1991; 88: 43-53Abstract Full Text PDF PubMed Scopus (154) Google Scholar performed a DBPC trial of a rush SCIT protocol in 70 immunotherapy-naive adults with allergic rhinitis (with or without asthma). Patients monosensitized to orchard grass received orchard grass extract SCIT or a placebo, whereas polysensitized patients received SCIT with the same dose of orchard grass extract and up to 3 other (many seasonal) allergens. Only the monosensitized patients showed a significant clinical effect of the standardized active treatment versus placebo. The authors suggested that polysensitized patients might require higher doses of allergen for equivalent efficacy.Kim et al24Kim K.W. Kim E.A. Kwon B.C. Kim E.S. Song T.W. Sohn M.H. et al.Comparison of allergic indices in monosensitized and polysensitized patients with childhood asthma.J Korean Med Sci. 2006; 21: 1012-1016Crossref PubMed Scopus (37) Google Scholar also compared multiallergen SCIT in polysensitized patients with single-allergen SCIT in monosensitized patients. The study investigated 130 children with allergic asthma: 62 (mean ± SD age, 7.6 ± 0.3 years) were polysensitized to HDM and an average of 4 other allergens and received corresponding mixtures, whereas 68 (mean ± SD age, 6.3 ± 0.3 years) were monosensitized to HDM and received HDM-only extracts. Both groups received the same dose of HDM antigen. The (nonoptimal) scoring system comprised a single interview-based assessment of dyspnea, wheezing, and cough intensity (on a 0- to 2-point scale) before immunotherapy and then again after at least 18 months of immunotherapy. The polysensitized patients had a signif
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