Empfehlungen zur Überprüfung der Wirksamkeit und Verlaufsdokumentation von Mepolizumab bei chronischer Rhinosinusitis mit Nasenpolypen (CRSwNP) im deutschen Gesundheitssystem ­ Empfehlungen des Ärzteverbandes Deutscher Allergologen (AeDA) und der AGs Klinische Immunologie, Allergologie und Umweltmedizin und Rhinologie und Rhinochirurgie der Deutschen Gesellschaft für HNO-Heilkunde, Kopf- und Halschirurgie (DGHNOKHC).

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the mucous membranes of the nose and sinuses. Eosinophilic inflammation is described as a common endotype. The anti-IL5 antibody mepolizumab was approved in November 2021 as an add-on therapy to intranasal glucocorticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps when systemic glucocorticosteroids or surgery do not provide adequate disease control. While national and international recommendations exist for the use of mepolizumab in CRSwNP, it has not yet been adequately specified how this therapy is to be monitored, what follow-up documentation is necessary, and when it should be terminated if necessary. METHODS: A literature search was performed to analyze previous data on the treatment of CRSwNP with mepolizumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to and including 10/2022 were considered. RESULTS: Based on the international literature and previous experience by an expert panel, recommendations for follow-up, adherence to therapy intervals and possible therapy breaks, as well as termination of therapy when using mepolizumab for the indication CRSwNP in the German health care system are given on the basis of a documentation sheet. CONCLUSIONS: Understanding the immunological basis of CRSwNP opens up new non-surgical therapeutic approaches with biologics for patients with severe, uncontrolled courses. Here, we provide recommendations for follow-up, adherence to therapy intervals, possible therapy pauses, or discontinuation of therapy when mepolizumab is used as add-on therapy with intranasal glucocorticosteroids to treat adult patients with severe CRSwNP that cannot be adequately controlled with systemic glucocorticosteroids and/or surgical intervention.

New European Academy of Allergy and Clinical Immunology definition on pollen season mirrors symptom load for grass and birch pollen-induced allergic rhinitis.

BACKGROUND: The use of allergen immunotherapy (AIT) for allergic rhinitis and its clinical efficacy in clinical trials depends on the effective determination of pollen allergen exposure time periods. We evaluate pollen data from Germany to examine the new definitions on pollen season and peak pollen period start and end as proposed by the European Academy of Allergy and Clinical Immunology (EAACI) in a recently published Position Paper. The aim was to demonstrate the ability of these definitions to mirror symptom loads for grass and birch pollen-induced allergic rhinitis based on real-life data. METHODS: Data coming from four pollen monitoring stations in the Berlin and Brandenburg area in Germany and for 3 years (2014-2016) were used to investigate the correlation of season definitions, birch and grass pollen counts and total nasal symptom and mediation scores as reported by patients in "Patients Hay fever Diaries" (PHDs). After the identification of pollen periods on the basis of the EACCI criteria, a statistical analysis was employed, followed by a detailed graphical investigation. RESULTS: The analysis revealed that the definitions of pollen season as well as peak pollen period start and end as proposed by the EAACI are correlated to symptom loads for grass and birch pollen-induced allergic rhinitis reported by patients in PHDs. CONCLUSION: Based on our analysis, the validity of the EAACI definitions on pollen season is confirmed. Their use is recommended in future clinical trials on AIT as well as in daily routine for optimal patient care.

Randomized controlled trials define shape of dose response for Pollinex Quattro Birch allergoid immunotherapy.

BACKGROUND: The Birch Allergoid, Tyrosine Adsorbate, Monophosphoryl Lipid A (POLLINEX® Quattro Plus 1.0 ml Birch 100%) is an effective, well-tolerated short course subcutaneous immunotherapy. We performed 2 phase II studies to determine its optimal cumulative dose. METHODS: The studies were conducted in Germany, Austria and Poland (EudraCT numbers: 2012-004336-28 PQBirch203 and 2015-000984-15 PQBirch204) using a wide range of cumulative doses. In both studies, subjects were administered 6 therapy injections weekly outside the pollen season. Conjunctival Provocation Tests were performed at screening, baseline and 3-4 weeks after completing treatment, to quantify the reduction in Total Symptom Scores (as the primary endpoint) with each cumulative dose. Multiple Comparison Procedure and Modeling analysis was used to test for the dose response, shape of the curve and estimation of the median effective dose (ED50 ), a measure of potency. RESULTS: Statistically significant dose responses (P < .01 & .001) were seen, respectively. The highest cumulative dose in PQBirch204 (27 300 standardized units [SU]) approached a plateau. Potency of the PQBirch was demonstrated by an ED50 2723 SU, just over half the current dose. Prevalence of treatment-emergent adverse events was similar for active doses, most being short-lived and mild. Compliance was over 85% in all groups. CONCLUSION: Increasing the cumulative dose of PQBirch 5.5-fold from 5100 to 27 300 SU achieved an absolute point difference from placebo of 1.91, a relative difference 32.3% and an increase in efficacy of 50%, without compromising safety. The cumulative dose response was confirmed to be curvilinear in shape.

Short course of grass allergen peptides immunotherapy over 3 weeks reduces seasonal symptoms in allergic rhinoconjunctivitis with/without asthma: A randomized, multicenter, double-blind, placebo-controlled trial.

BACKGROUND: Immunotherapy with peptide hydrolysates from Lolium perenne (LPP) is an alternative treatment for seasonal allergic rhinitis with or without asthma. The aim of this study was to assess the clinical efficacy and safety of a cumulative dose of 170 µg LPP administered subcutaneously over 3 weeks. METHODS: In a randomized, double-blind, placebo-controlled trial, 554 adults with grass pollen rhinoconjunctivitis were randomized (1:2 ratio) to receive 8 subcutaneous injections of placebo or 170 µg LPP administered in increasing doses in 4 visits over 3 weeks. The primary outcome was the combined symptom and medication score (CSMS) measured over the peak pollen season. Reactivity to conjunctival provocation test (CPT) and quality of life (QOL) was assessed as secondary endpoints. RESULTS: The mean reduction in CSMS in the LPP vs placebo group was -15.5% (P = .041) during the peak period and -17.9% (P = .029) over the entire pollen season. LPP-treated group had a reduced reactivity to CPT (P < .001) and, during the pollen season, a lower rhinoconjunctivitis QOL global score (P = .005) compared with placebo group. Mostly mild and WAO grade 1 early systemic reaction (ESR) were observed ≤30 minutes in 10.5% of LPP-treated patients, whereas 3 patients with a medical history of asthma (<1%) experienced a serious ESR that resolved with rescue medication. CONCLUSION: Lolium perenne pollen peptides administered over 3 weeks before the grass pollen season significantly reduced seasonal symptoms and was generally safe and well-tolerated.

Ultra-short-course booster is effective in recurrent grass pollen-induced allergic rhinoconjunctivitis.

BACKGROUND: A relevant proportion of allergic rhinoconjunctivitis (ARC) patients experience recurrent symptoms after successfully completing allergen immunotherapy (AIT). This prospective, controlled, noninterventional study used internationally standardized instruments to determine the clinical effects of a preseasonal, ultra-short-course booster AIT on clinical outcome parameters. METHODS: This two-arm study included patients aged ≥12 years with recurrent grass pollen-induced seasonal AR who had completed a successful course of any grass pollen AIT at least 5 years before enrolment. Overall, 56 patients received one preseasonal short-course booster AIT using tyrosine-absorbed grass pollen allergoids containing the adjuvant monophosphoryl lipid A (MPL® ); 51 control patients received symptomatic medication. The combined symptom and medication score (CSMS) was recorded in the (peak) grass pollen season. Furthermore, concomitant (antiallergic) medication use, the patients' state of health, Mini Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ) results and safety/tolerability of the treatment were assessed. RESULTS: The CSMS in the peak grass pollen season was significantly lower in the booster AIT group (Δ=38.4%, P<.01). Moreover, significantly more patients in this group used no concomitant antiallergic medication throughout the peak grass pollen season. Twice as many patients in the booster AIT group as in the control group reported having a better state of health than in the preceding season. MiniRQLQ results showed significant differences favouring the booster AIT. The booster AIT was generally well tolerated, with only two patients reporting mild, grade 1 systemic adverse events. CONCLUSION: Booster AIT using tyrosine-absorbed allergoids containing the adjuvant MPL® effectively prevents re-occurrence of symptoms in patients with grass pollen-induced ARC.

Dose-response relationship of a new Timothy grass pollen allergoid in comparison with a 6-grass pollen allergoid.

BACKGROUND: Subcutaneous allergen immunotherapy with grass pollen allergoids has been proven to be effective and safe in the treatment of patients with allergic rhinoconjunctivitis. Based on the extensive cross-reactivity among Pooideae species, it has been suggested that grass pollen extracts could be prepared from a single species, rather than from a multiple species mixture. OBJECTIVE: To find the optimal dose of a Phleum pratense (P. pratense) allergoid preparation and compare its efficacy and safety to a 6-grass pollen allergoid preparation. METHODS: In this double-blind, placebo-controlled study (EudraCT: 2011-000674-58), three doses of P. pratense allergoid (1800 therapeutic units (TU), standard-dose 6000 TU and 18 000 TU) were compared with placebo and the marketed 6-grass pollen allergoid (6000 TU). In a pre-seasonal dosing regimen, 102 patients were randomized to five treatment groups and received nine subcutaneous injections. The primary efficacy endpoint was the change in weal size (late-phase reaction [LPR]) in response to the intracutaneous testing (ICT) before and after treatment, comparing the active allergoids to placebo. Secondary outcomes were the change in Total Nasal Symptom Score (TNSS) assessed in the allergen exposure chamber (AEC), the changes in P. pratense-serum-specific IgG4 and the incidence of adverse events (AEs). RESULTS: All three doses of the P. pratense and the 6-grass pollen allergoid preparations were significantly superior to placebo for the primary outcome, whereas there were no significant differences in the change in TNSS. Compared to the standard-dose, the high-dose of P. pratense did not produce any additional significant benefit, but showed a slight increase in AEs. Yet this increase in AEs was lower than for the 6-grass pollen preparation. CONCLUSIONS & CLINICAL RELEVANCE: The standard-dose of the new P. pratense allergoid was comparable to the marketed 6-grass pollen preparation at equal dose for the parameters measured.

Defining pollen exposure times for clinical trials of allergen immunotherapy for pollen-induced rhinoconjunctivitis - an EAACI position paper.

BACKGROUND: Clinical efficacy of pollen allergen immunotherapy (AIT) has been broadly documented in randomized controlled trials. The underlying clinical endpoints are analysed in seasonal time periods predefined based on the background pollen concentration. However, any validated or generally accepted definition from academia or regulatory authorities for this relevant pollen exposure intensity or period of time (season) is currently not available. Therefore, this Task Force initiative of the European Academy of Allergy and Clinical Immunology (EAACI) aimed to propose definitions based on expert consensus. METHODS: A Task Force of the Immunotherapy and Aerobiology and Pollution Interest Groups of the EAACI reviewed the literature on pollen exposure in the context of defining relevant time intervals for evaluation of efficacy in AIT trials. Underlying principles in measuring pollen exposure and associated methodological problems and limitations were considered to achieve a consensus. RESULTS: The Task Force achieved a comprehensive position in defining pollen exposure times for different pollen types. Definitions are presented for 'pollen season', 'high pollen season' (or 'peak pollen period') and 'high pollen days'. CONCLUSION: This EAACI position paper provides definitions of pollen exposures for different pollen types for use in AIT trials. Their validity as standards remains to be tested in future studies.

A randomized DBPC trial to determine the optimal effective and safe dose of a SLIT-birch pollen extract for the treatment of allergic rhinitis: results of a phase II study.

BACKGROUND: Sublingual immunotherapy (SLIT) is a potential efficacious and safe treatment option for patients with respiratory, IgE-mediated allergic diseases. A combined tolerability, dose-finding study with a sublingual liquid birch pollen preparation (SB) was conducted. METHODS: Two hundred and sixty-nine adults with birch-pollen-induced AR were randomized to placebo, SB: 3333, 10,000, 20,000 or 40,000 AUN/ml. Differences in symptom scores following a titrated nasal provocation test (TNPT) at baseline and after 5 months of treatment were determined. Safety, tolerability, birch-pollen-specific immunoglobulin levels and peak nasal inspiratory flow (PNIF) were also measured (all measures determined outside the birch pollen season). RESULTS: In all treatment groups, an improvement in symptom scores after treatment compared to baseline was observed, with an additional stepwise improvement in the active groups compared to placebo, which was significant in high-dose groups (P = 0.008 and P < 0.001, respectively). For this primary endpoint, a significant linear dose-response curve was observed: the higher the dose, the better the improvement observed. Likewise, active treatment resulted in an increase in PNIF and serum IgG levels compared to placebo. The highest improvements were found in the 40,000 AUN/ml group. All active dosages resulted in more adverse reactions than placebo, which were mainly mild and well-controlled. CONCLUSIONS: A multicentre trial evaluated the dose-response and tolerability of SB. All active treatment groups showed better responses than placebo for both primary and secondary parameters. The results indicate that, within the studied dose range, SB 40,000 AUN/ml is the most optimal effective and safe dose (ClinicalTrials.gov: NCT01639768).

A high polymerized grass pollen extract is efficacious and safe in a randomized double-blind, placebo-controlled study using a novel up-dosing cluster-protocol.

BACKGROUND: Cluster immunotherapy represents an interesting alternative to conventional up-dosing schedules because it allows achieving the maintenance dose within a shorter time interval. In this study, the efficacy and safety of cluster immunotherapy with a high polymerized allergen extract of a grass/rye pollen mixture have been evaluated in a randomized, double-blind, placebo-controlled, multicenter study. METHODS: In total, 121 patients with allergic rhinoconjunctivitis due to grass pollen were randomized 1 : 1 to verum or placebo group. A short cluster up-dosing schedule of only 1 week was applied to achieve the maintenance dose which was administered monthly during the study period of 1 year. Total combined symptom and medication score (TCS) was defined as primary outcome parameter. Secondary outcome parameters were individual symptom and medication scores, 'well days,' global improvement as well as immunological effects and nasal allergen challenge. The safety profile was evaluated based on the European academy of allergy and clinical immunology grading system. RESULTS: Significant reduction in the verum compared to the placebo group (intention-to-treat, population, verum: n = 55; placebo: n = 47) was found regarding TCS (P = 0.005), rhinoconjunctivitis total symptom score (RTSS, P = 0.006), and total rescue medication score (TRMS, P = 0.002). Additionally, secondary outcomes such as 'well days,' nasal challenge results, and increase of specific IgG4 were in favor of the active treatment. All systemic adverse reactions (0.8% of all injections in the verum group) were of mild intensity. No severe reactions related to the study medication were observed. CONCLUSION: Cluster immunotherapy with high polymerized grass pollen extracts resulted in significant clinical efficacy and has been shown to be a safe treatment for grass pollen-allergic patients.

Depigmented-polymerized mixed grass/birch pollen extract immunotherapy is effective in polysensitized patients.

BACKGROUND: Although many patients with allergic rhinoconjunctivitis have symptoms due to sensitization with more than one pollen allergen, and mixed pollen extracts are widely used for allergen immunotherapy in practice, there are few published trials. METHODS: We performed a 2-year multicentre, double-blind, placebo-controlled trial of subcutaneous immunotherapy with mixed depigmented-polymerized birch and grass pollen extract in 285 patients with allergic rhinoconjunctivitis symptomatic during both birch and grass pollen seasons. Primary outcome was combined symptom and medication score (SMS) assessed by daily visual analogue scales (VAS). Analysis included a placebo-based analysis examining the effect of treatment only on days when placebo patients were symptomatic. RESULTS: There was a significant reduction in median SMS for actively treated patients (median 5.70 (interquartile range 2.62-10.02) compared with 7.07 (3.47-10.71) for placebo, P = 0.0385). Rhinitis quality-of-life scores were significantly better for active compared with placebo, and other secondary endpoints were not significantly different. Placebo-based analysis showed a 33.7% reduced SMS at year 2 for active treatment compared with placebo on days when placebo patients were symptomatic. Both birch pollen- and grass pollen-specific IgG4 increased with active treatment. CONCLUSIONS: This study shows efficacy of mixed pollen extracts for immunotherapy for patients symptomatic to both birch and grass pollen allergens. The relatively modest effect may reflect 50% dose reduction for each allergen in the mixture. It supports VAS for symptom assessment and placebo-based analysis as useful for the analysis of immunotherapy trials. The safety of modified extracts may allow study of mixed extracts without dose reduction to improve efficacy.

Specific subcutaneous immunotherapy with recombinant grass pollen allergens: first randomized dose-ranging safety study.

BACKGROUND: Allergen-specific immunotherapy (SIT) with native allergen extracts and allergoids has been performed successfully for decades. Preliminary studies revealed the use of recombinant allergen-preparations as a promising option for SIT. OBJECTIVE: The present study was designed to investigate the dose-ranging safety in SCIT with a mixture of five recombinant grass pollen allergens containing equimolar amounts of rPhl p 1, rPhl p2, rPhl p 5a, rPhl p 5b and rPhl p 6, adsorbed to aluminium hydroxide. METHODS: A randomized, double blind, placebo-controlled, dose-ranging safety study (EudraCT number 2007-002808-18) was performed in 50 patients with allergic rhinoconjunctivitis, with or without asthma. Patients were randomized to groups of 10 to receive maximum doses of 20, 40, 80 or 120 µg of total grass pollen recombinant protein or placebo. The primary end-point of this trial was the number of patients with at least one systemic reaction with possible, probable or definite relationship to the study medication determined at the end of the up-dosing phase. Secondary end-points included titrated intracutaneous test with natural six-grass pollen extract, allergen-specific conjunctival provocation test as well as IgG and IgE-levels throughout the study. RESULTS: Eight of the 50 patients revealed systemic reactions grade 1 or 2 corresponding to the primary end-point definition. No systemic reactions grade 3 or 4 occurred in any dosage group. The systemic reactions were well distributed among the active groups. Results of secondary end-points imply that the study medication is effective and provokes immunological effects. CONCLUSIONS AND CLINICAL RELEVANCE: The first DBPC SCIT-DRF with a mixture of recombinant Phleum allergens (Phl p 1, 2, 5a, 5b, 6) in patients with rhinoconjunctivitis plus/minus asthma showed no major side effects in very high doses up to 120 µg.

Cyclamen europaeum nasal spray, a novel phytotherapeutic product for the management of acute rhinosinusitis: a randomized double-blind, placebo-controlled trial.

AIM: To evaluate the efficacy and safety of a phytotherapeutic nasal spray containing Cyclamen europaeum (CE) in the treatment of acute rhinosinusitis (ARS). MATERIAL/METHODS: We performed a randomized, double-blind, placebo-controlled trial of CE nasal spray once daily for 15 days in 99 adult patients with moderate-to-severe ARS who also received amoxicillin 500 mg three times daily for the first 8 days. The primary endpoint was the change in mean total symptom scores (TSS) on day 7. Secondary endpoints included individual symptom scores (nasal congestion, mucus secretion, facial pain, impairment of smell) and endoscopic findings on days 7 and 15 and others. RESULTS: No statistically significant difference in TSS was noted for CE versus placebo on day 7. Moreover, the individual scores were not statistically different between the groups for the ITT-population on day 7. However, both a reduction in facial pain and an improvement in endoscopically-assessed mucosal obstruction significantly favoured CE on day 7. The most common adverse events were nasal burning and mild epistaxis, but no severe adverse events were documented. CONCLUSION: In summary, this is the first randomized controlled trial on phytotherapy in patients with moderate-to-severe ARS demonstrating clinical safety and some encouraging effects of CE which merit to investigate phytotherapeutic products in further large-scale clinical trials.

A randomized placebo-controlled trial of rush preseasonal depigmented polymerized grass pollen immunotherapy.

BACKGROUND: Specific subcutaneous immunotherapy (SCIT) for seasonal rhinoconjunctivitis with unmodified allergen extracts is effective, but limited by risk of side-effects and involves treatment over 3 years. We examined a depigmented polymerized grass pollen extract for immunogenicity and for clinical efficacy in a rush preseasonal regimen. METHODS: Depigmented polymerized grass pollen extract was tested for proliferation and cytokine production by peripheral blood mononuclear cells. A prospective, double-blind, placebo-controlled trial of 195 grass pollen allergic patients treated with preseasonal rush immunotherapy using depigmented polymerized allergenic extract of mixed grass pollen was performed over 2 years. Primary outcome was combined symptom and medication score (SMS) during the peak of the second grass pollen season. Secondary outcomes included combined score over the whole season, during the first grass pollen season, individual symptom and medication scores, quality of life, well days/hell days and responder analysis. Adverse events were classified using the EAACI scale. Grass pollen-specific IgE and IgG4 were measured before and during treatment. RESULTS: Depigmented polymerized extract stimulated dose-dependent T-cell proliferation and cytokine production. Patients treated with preseasonal SCIT showed improved combined scores during peak season at year 2 (median 3.93, interquartile range 0.77-6.27 vs median 5.86 for placebo, 3.11-8.36, P < 0.01). Most secondary outcomes were significantly better for active treatment. Side-effects were minimal, with no grade 3 or 4 reactions. CONCLUSIONS: Depigmented polymerized grass pollen extract is immunogenic and clinically effective in rush preseasonal SCIT. This form of immunotherapy may be an attractive option for some patients.

Sustained clinical efficacy of sublingual immunotherapy with a high-dose grass pollen extract.

BACKGROUND: Sublingual immunotherapy (SLIT) with a high-dose 6-grass pollen SingleDose preparation was shown to be effective and safe in a 2-year randomized, double-blind, placebo-controlled trial. OBJECTIVE: We evaluated the effect of the third year of SLIT in comparison to the second year. METHODS: 46 grass pollen-allergic patients who had received active treatment for 3 consecutive years were included in the safety set. Diary data from 39 subjects were evaluated to calculate symptom and medication scores as well as 'well days'. RESULTS: Symptoms and medication intake further decreased in the third year of SLIT during the grass pollen season in comparison to the previous years and the number of 'well days' increased accordingly. No serious adverse events occurred during the three years of SLIT. CONCLUSION: The third year of SLIT with the high-dose 6-grass pollen preparation results in sustained and even further increased clinical efficacy.

[Recording cervical and ocular vestibular evoked myogenic potentials. Part 2: influencing factors, evaluation of findings and clinical significance]. / Die Ableitung zervikaler und okulärer vestibulär evozierter myogener Potenziale. Teil 2: Einflussfaktoren, Bewertung der Befunde und klinische Bedeutung.

VEMP measurements are subject to various influencing factors: patient age, threshold, sound intensity and frequency. Using air (AC) and bone conduction (BC) the vestibular receptors and afferents of the otolith organs can be activated to varying degrees. Recordings of cervical (cVEMP) and ocular VEMP (oVEMP) are clinically possible. AC-cVEMP are primarily an indicator of the sacculocollic reflex pathway. Together with findings on the vestibuloocular reflex (VOR) and complimentary otolith tests, VEMP enable otolith function analysis of each side separately. In addition, the distinction between combined or isolated canal and otolith dysfunction in terms of subtyping and patterns of damage in mono- and bilateral disorders, such as vestibular neuritis or bilateral vestibulopathy, is possible. Moreover, VEMP is relevant in terms of prognostic and therapeutic considerations as well as expert assessments.

[Recording cervical and ocular vestibular evoked myogenic potentials: part 1: anatomy, physiology, methods and normal findings]. / Die Ableitung zervikaler und okulärer vestibulär evozierter myogener Potenziale: Teil 1: Anatomie, Physiologie, Methodik und Normalbefunde.

Vestibular evoked myogenic potentials (VEMP) have gained in clinical significance in recent years, now forming an integral part of neurootological examinations to establish the functional status of the otolith organs. They are sensitive to low-frequency acoustic stimuli. When stimulated, receptors in the sacculus and utriculous are activated. By means of reflexive connections, myogenic potentials can be recorded when the relevant muscles are tonically activated. The vestibulocolic (sacculocollic) reflex travels from the otolith organs over the central circuitry to the ipsilateral sternocleidomastoid muscle. Myogenic potentials can be recorded by means of cervical VEMP (cVEMP). The vestibuloocular reflex crosses contralaterally to the extraocular eye muscle. Ocular VEMP (oVEMP) are recorded periocularly, preferably from the inferior oblique muscle. Various stimulation methods are used including air conduction and bone conduction.

Immunotherapy with depigmented-polymerized mixed tree pollen extract: a clinical trial and responder analysis.

BACKGROUND: Rhinoconjunctivitis because of tree pollen sensitization is common in Northern Europe. Specific subcutaneous immunotherapy (SCIT) is the only disease-modifying treatment, but unmodified allergen extracts carry a risk of allergic side-effects. Our objective was to examine efficacy and safety of a depigmented-polymerized mixed tree pollen extract. METHODS: A double-blind, placebo-controlled trial of 184 tree pollen allergic adults was performed. SCIT consisted of four increasing doses at 7-day intervals, then maintenance injections every 6 weeks for 18 months. Primary outcome was combined symptom and medication score during the 2008 season. Secondary outcomes included analysis at different levels of pollen exposure and a responder analysis. Adverse events were classified using the EAACI scale. Birch pollen-specific IgE and IgG(4) were measured before and after treatment. RESULTS: The combined symptom and medication score of actively treated patients was significantly lower than those on placebo (P < 0.04). Increased efficacy was seen at high pollen exposure (median score 2.1 for active [IQR 0.7-3.4] vs 4.2 [IQR 2.4-5.3] for placebo for days with 500 or more pollen grains per m(3) , a 50% reduction, P < 0.01). A modified responder analysis revealed 64% responders in the active and 32% in the placebo group (P < 0.01). There were 17 systemic reactions. All were mild (grade 1 or 2) and required no treatment. Serum birch-specific IgG(4) increased in the SCIT group (P < .01). CONCLUSIONS: SCIT with depigmented- polymerized tree pollen extract was clinically effective and well tolerated. Responder analysis suggested that one-third of patients treated with immunotherapy may not respond.

[Specific immunotherapy with depigmented allergoids]. / Depigmentierte Allergoide für die allergenspezifische Immuntherapie.

Specific immunotherapy is the only available causative treatment for IgE-mediated allergic conditions. The state of the art is treatment via the subcutaneous route with crude extracts in a water solution, with physically linked (semidepot) extracts or chemically modified semidepot extracts (allergoids). A relatively new purification method combines depigmentation followed by polymerization with glutaraldehyde. This modification results in increased tolerance with a reduction in both local and systemic adverse effects. As controlled clinical trials have shown, the effectiveness is comparable to that of specific immunotherapy with crude allergen extracts. Recent data suggest that the modified polymerized allergoids allow a safe rush titration in a few days or even in 1 day (ultra-rush titration).