Conjunctival Provocation Test Research Articles

Strong Dose-response Using a Conjunctival Provocation Test During a Phase II Allergen Immunotherapy Study With Subcutaneously Administered Tyrosine Adsorbed Modified Grass Allergen + MPL

Strong Dose-response Using a Conjunctival Provocation Test During a Phase II Allergen Immunotherapy Study With Subcutaneously Administered Tyrosine Adsorbed Modified Grass Allergen + MPL

Conjunctival Provocation Test in Diagnosis of Peanut Allergy in Children

H Lindvik, Carlsen KC Lodrup, P Mowinckel, J Navaratnam, MP Borres, KH Carlsen. Clin Exp Allergy. 2017;47(6):785–794 To investigate whether the conjunctival provocation test (CPT) may be an alternative to oral food challenge (OFC) for the diagnosis of peanut allergy. The primary aim in this study was to assess the diagnostic value of the CPT. Secondary aims were evaluating the predictive value of the CPT for peanut anaphylactic reactions and examining the safety of the CPT. This cross-sectional, case-control study included 102 children with clinical or laboratory-suspected peanut allergy and a control group of 28 children of similar age who were peanut tolerant. A previous clinical adverse reaction to peanut was …

CONJUNCTIVAL PROVOCATION TESTING IN A DOSE FINDING STUDY WITH SUBCUTANEOUS IMMUNOTHERAPY WITH GRASS + MPL

Introduction The total symptom score (TSS) measured during conjunctival provocation testing (CPT) was used as primary endpoint of a Phase II study to evaluate the dose response for a subcutaneous immunotherapy (SCIT) product (1.0 ml) with modified allergen tyrosine adsorbate (MATA) and monophosphoryl lipid A (MPL) adjuvants developed for treatment of allergic rhinoconjunctivitis due to grass pollen [EudraCT 2017-000333-31]. Doses of 5100, 14400, 27600 and 35600 standardized units (SU) and placebo were evaluated. Methods CPTs were performed at screening, pre-dose and approximately 4 weeks post-treatment. TSS was calculated as the sum of 4 symptoms (eye redness, tearing, itching and irritation), each scored on a 4-point scale. Concentrations of 0.3, 1.0, 3.0, 10 and 30 Histamine Equivalent Potency units (HEP)/mL were available for testing. A TSS ≥ 6 points was required at screening and pre-dose. Results The blinded results showed a mean TSS of 7.5 (95% CI: 7.3-7.6) and 4.4 points (95% CI: 4.2-4.7) at pre-dose and post-treatment, respectively. For 251 patients of the 426 patients (58.9%) a positive post-treatment CPT was achieved at least one higher concentration of allergen compared to pre-dose. Conclusions In this Phase II study, CPT was used to establish a dose response of a grass MATA MPL SCIT product using a wide range of cumulative dose regimens. The blinded results indicate adequate CPT performance which may well support the selection of the optimal dose for Phase III, which would be an important milestone in the development of an efficacious and safe pre-seasonal state-of-the-art grass SCIT.

Conjunctival provocation tests: prediction of seasonal allergy.

The conjunctival provocation test (CPT) is often used to clearly identify the specific allergen causing the symptoms of allergic rhinoconjunctivitis but also to assess the clinical efficacy of an allergen immunotherapy (AIT). As there is no consensus about its predictive value, the aim of this publication is to evaluate under which conditions the CPT can predict the symptom severity during the allergy season after previous AIT. Three out of four randomized controlled trials (RCTs) showed a correlation between CPT reactivity and symptoms occurring under natural allergen exposure after previous AIT. Furthermore, one RCT found that performing the CPT 4 weeks after initiating AIT can identify early responders who also show a benefit during the season. Another RCT suggested that conducting the CPT prior to starting AIT can be used to identify patients who may benefit more from treatment than others. The assessment of the reviewed literature led us to the conclusion that the CPT has a predictive value and can consequently be used to assess the efficacy of an administered AIT if performed according to a standardized challenge protocol with high-quality allergen extracts.

Early nonreactivity in the conjunctival provocation test predicts beneficial outcome of sublingual immunotherapy

BackgroundClinical practice needs a common parameter that can provide an early, reliable estimation of the outcome of sublingual immunotherapy (SLIT) in an upcoming pollen season. We investigated whether the conjunctival provocation test (CPT) can predict the beneficial outcome of SLIT in patients with allergic rhinoconjunctivitis after 4 weeks of treatment.MethodsWe conducted two separate prospective, randomized, double-blind, placebo-controlled, multicenter trials. Adults 18–75 years of age received placebo or SLIT tablets containing tree or grass pollen allergoids and underwent CPTs. Participants receiving SLIT were divided into two groups (reactive, nonreactive) according to their CPT reactions after 4 weeks of treatment. These two groups were compared with regard to clinical outcome parameters (total combined score, rhinoconjunctivitis total symptom score, total rescue medication score, well days) assessed during the pollen season for the 14-day (tree) or 30-day (tree/grass) peaks and for the entire 60-day seasons. Participants’ global evaluations of therapy after completing treatment were also compared.ResultsThe tree pollen trial randomized 188 participants; 182 participants were evaluable, 76 of whom received SLIT and were suitable for this post hoc analysis. The grass pollen trial included 90 participants; 82 participants were evaluable, 44 of whom underwent SLIT. Comparing SLIT participants who reacted to the CPT after 4 weeks (tree: 77.6%; grass: 79.5%) with those who ceased to show a reaction (tree: 22.4%; grass: 20.5%) (tree: P = 0.0001; grass: P = 0.003), the total combined score for the 14-day (P = 0.017) and 30-day peaks (P = 0.042) as well as the rhinoconjunctivitis total symptom score assessed for the 14-day peak (P = 0.024) were significantly lower in the nonreactive group of the tree pollen trial. In the grass pollen trial, the nonreactive group rated their SLIT treatment significantly better (P = 0.019).ConclusionsUsing clinically meaningful outcome parameters during the pollen season, both trials independently led to similar results when comparing participants’ reactions to the CPT 4 weeks after beginning SLIT. These results suggest that CPT allows an early estimation of allergic rhinoconjunctivitis symptoms before an upcoming season. Thus, the CPT can be used as a valuable parameter to predict the beneficial outcome of ongoing SLIT.Trial registrationBoth trials registered with the Medical Ethics Committee of the North Rhine Medical Council (EudraCT numbers 2012-004916-79 (grass pollen trial) and 2013-002129-43 (tree pollen trial)) and the German Federal Ministry of Health (Paul-Ehrlich-Institut).

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

BackgroundThe 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.MethodsThe 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 (ED 50), a measure of potency.ResultsStatistically 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 ED 50 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.ConclusionIncreasing 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.

Reliability of a New Symptom Score in a Titrated Quantitative Conjunctival Provocation Test Supported by an Objective Photodocumentation

Background: Allergen provocation tests are useful methods for proving the clinical relevance of an allergen-specific sensitization. Among these methods, the conjunctival provocation test (CPT) represents an easy-to-use tool. However, its readout parameters have not yet been internationally standardized or validated. Photodocumentation has been shown as a good option for objectifying a CPT reaction, supporting the local investigator assessment. Based on test-retest reliability of the score and an objective digital photoanalysis of the conjunctival redness, this study aimed to prove the reproducibility of a new CPT scoring system for use in clinical trials (ClinicalTrials.gov identifier: NCT02690740). Methods: A titrated quantitative CPT was conducted outside of the pollen season in a final cohort of 23 adult patients with birch or grass pollen-induced allergic rhinoconjunctivitis. Conjunctival symptoms were analyzed using a standardized symptom score. Conjunctival redness was also evaluated by an external observer and correlated with a digital photoanalysis using MATLAB software. Results: A test-retest correlation of 0.6 (p < 0.01) was found for the symptom score results. Likewise, a correlation of 0.65 (p < 0.01) was observed in the digital photoanalysis. The total symptom score showed a decrease in the mean value of 0.48 score points in the retest. Conclusions: This study reveals both a valuable test-retest correlation of the proposed score as well as a good correlation of eye redness with the (objective) photodocumentation. Based on our results, we can recommend the use of this scoring system as a valuable clinical protocol for future clinical trials.

Lolium perenne peptide immunotherapy is well tolerated and elicits a protective B-cell response in seasonal allergic rhinitis patients.

BackgroundSystemic allergic reactions are a risk for allergen immunotherapy that utilizes intact allergen preparations. We evaluated the safety, efficacy and immune mechanisms of short‐course treatment with adjuvant‐free Lolium perenne peptides (LPP) following a 6‐week dose‐escalation protocol.MethodsIn a prospective, dose‐escalation study, 61 grass pollen–allergic patients received 2 subcutaneous injections of LPP once weekly for 6 weeks. Safety was assessed evaluating local reactions, systemic reactions and adverse events. The clinical effect of LPP was determined by reactivity to the conjunctival provocation test (CPT). Specific IgE, IgG4 and blocking antibodies were measured at baseline (V1), during (V6) and after treatment (V8).ResultsNo fatality, serious adverse event or epinephrine use was reported. Mean wheal diameters after injections were <0.6 cm and mean redness diameters <2.5 cm, independent of dose. Transient and mostly mild adverse events were reported in 33 patients. Two patients experienced a grade I and 4 patients a grade II reaction (AWMF classification). At V8, 69.8% of patients became nonreactive to CPT. sIgG4 levels were higher at V6 (8.1‐fold, P < .001) and V8 (12.2‐fold, P < .001) than at V1. The sIgE:sIgG4 ratio decreased at V6 (−54.6%, P < .001) and V8 (−71.6%, P < .001) compared to V1. The absolute decrease in IgE‐facilitated allergen binding was 18% (P < .001) at V6 and 25% (P < .001) at V8.ConclusionIncreasing doses of subcutaneous LPP appeared safe, substantially diminished reactivity to CPT and induced blocking antibodies as early as 4 weeks after treatment initiation. The benefit/risk balance of LPP immunotherapy remains to be further evaluated in large studies.

Comparison of symptoms during a conjunctival provocation test (CPT) and a controlled exposure to birch pollen in the Strasbourg Environmental Exposure Chamber (EEC) ( ALYATEC)

Comparison of symptoms during a conjunctival provocation test (CPT) and a controlled exposure to birch pollen in the Strasbourg Environmental Exposure Chamber (EEC) ( ALYATEC)

Predicting reactivity threshold in children with anaphylaxis to peanut.

Peanut allergy necessitates dietary restrictions, preferably individualized by determining reactivity threshold through an oral food challenge (OFC). However, risk of systemic reactions often precludes OFC in children with severe peanut allergy. We aimed to determine whether clinical and/or immunological characteristics were associated with reactivity threshold in children with anaphylaxis to peanut and secondarily, to investigate whether these characteristics were associated with severity of the allergic reaction during OFC. A double-blinded placebo-controlled food challenge (DBPCFC) with peanut was performed in 96 5- to 15-year-old children with a history of severe allergic reactions to peanut and/or sensitization to peanut (skin prick test [SPT] ≥3 mm or specific immunoglobulin E [s-IgE] ≥0.35 kUA/L). Investigations preceding the DBPCFC included a structured interview, SPT, lung function measurements, serological immunology assessment (IgE, IgG and IgG4 ), basophil activation test (BAT) and conjunctival allergen provocation test (CAPT). International standards were used to define anaphylaxis and grade the allergic reaction during OFC. During DBPCFC, all 96 children (median age 9.3, range 5.1-15.2) reacted with anaphylaxis (moderate objective symptoms from at least two organ systems). Basophil activation (CD63+ basophils ≥15%), peanut SPT and the ratio of peanut s-IgE/total IgE were significantly associated with reactivity threshold and lowest observed adverse events level (LOAEL) (all P < .04). Basophil activation best predicted very low threshold level (<3 mg of peanut protein), with an optimal cut-off of 75.8% giving a 93.5% negative predictive value. None of the characteristics were significantly associated with the severity of allergic reaction. In children with anaphylaxis to peanut, basophil activation, peanut SPT and the ratio of peanut s-IgE/total IgE were associated with reactivity threshold and LOAEL, but not with allergy reaction severity.

Dose-Finding Study of Carbamylated Monomeric Allergoid Tablets in Grass-Allergic Rhinoconjunctivitis Patients

To determine the optimal effective and safe dose of sublingual immunotherapy tablets containing carbamylated monomeric allergoids in patients with grass pollen-induced allergic rhinoconjunctivitis. In this prospective, randomized, double-blind, active-controlled, multicenter, Phase II study, four different daily doses were applied preseasonally for 12 weeks. Of 158 randomized adults, 155 subjects (safety population) received 300 units of allergy (UA)/day (n=36), 600 UA/day (n=43), 1000 UA/day (n=39), or 2000 UA/day (n=37). After treatment, 54.3, 47.6, 59.0 and 51.4% of patients, respectively, ceased to react to the highest allergen concentration in a conjunctival provocation test. Furthermore, the response threshold improved in 70.4, 62.9, 76.7 and 66.7% of patients, respectively. No serious adverse events occurred. This study found 1000 UA/day to be the optimal effective and safe dose.

Molecular diagnostics of ocular allergy

SummaryOcular allergies may severely impact on daily activities and overall quality of life. Conventional allergy testing with skin prick tests and circulating serum immunoglobulin E often falls short of identifying the culprit ocular allergens. On the other hand, targeting the ocular milieu may prove valuable for ocular allergy diagnostics. Conjunctival provocation testing and specific immunoglobulin E detection in tear fluid provide data on local ocular hypersensitivity. We focused on specific IgE testing by means of a commercial allergen microarray (ISAC® 112, Thermo Fisher Scientific). We report here the contribution of allergen microarray testing to identifying the culprit allergen in a 42‐year old woman presenting with perennial allergic conjunctivitis.

Conjunctival provocation test in diagnosis of peanut allergy in children.

Peanut allergy frequently causes severe allergic reactions. Diagnosis includes detection of IgE to peanuts in serum or by skin prick tests. While children may have allergic sensitization without having clinical peanut allergy, oral peanut challenge is often required for accurate diagnosis. The conjunctival provocation test is used for diagnosis and evaluation of treatment effect in inhalant allergies, but it has not been evaluated as a tool for diagnosing peanut allergy. To investigate whether the conjunctival provocation tests may be feasible, accurate and safe in diagnosing clinically relevant peanut allergy in patients with suspected peanut allergy. This cross-sectional case-control study in children with clinical or laboratory suspected peanut allergy included 102 children recruited from the regional paediatric departments and specialist practices during one year from April 2011. A peanut-tolerant control group of 28 children of similar age was recruited locally. A double-blind placebo-controlled conjunctival provocation test with peanut extract was performed in all children, while oral peanut provocation was performed as double-blind placebo-controlled challenge in children with suspected peanut allergy and as an open challenge in the control children. All 81 children with a positive double-blind placebo-controlled oral food challenge (OFC) also had a positive conjunctival provocation test. None of the children with negative conjunctival provocation test had a positive OFC. The sensitivity and the specificity of the conjunctival provocation test were 0.96 and 0.83, respectively. No children had severe adverse reaction caused by the conjunctival provocation test, whereas 23 children suffered an anaphylactic reaction to the OFC. Conjunctival allergen challenge appears to be feasible, accurate and safe in diagnosing children referred for suspected peanut allergy.

Conjunctival allergen provocation test : guidelines for daily practice.

Conjunctival allergen provocation test (CAPT) reproduces the events occurring by instilling an allergen on the ocular surface. This paper is the compilation of a task force focussed on practical aspects of this technique based on the analysis of 131 papers. Main mechanisms involved are reviewed. Indications are diagnosing the allergen(s)-triggering symptoms in IgE-mediated ocular allergy in seasonal, acute or perennial forms of allergic conjunctivitis, especially when the relevance of the allergen is not obvious or in polysensitized patients. Contraindications are limited to ongoing systemic severe pathology, asthma and eye diseases. CAPT should be delayed if receiving systemic steroids or antihistamines. Local treatment should be interrupted according to the half-life of each drug. Prerequisites are as follows: obtaining informed consent; evidencing of an allergen by skin prick tests and/or serum-specific IgE dosages; being able to deal with an unlikely event such as acute asthma exacerbation, urticaria or anaphylaxis, or an exacerbation of allergic conjunctivitis. Allergen extracts should be diluted locally prior to administration. Positive criteria are based on itching or quoted according to a composite score. An alternative scoring is based on itching. CAPT remains underused in daily practice, although it is a safe and simple procedure which can provide valuable clinical information.

Digitally Analyzed Conjunctival Redness: Does Repeated Conjunctival Provocation Intrinsically Cause Local Desensitization of the Eye?

Background: Allergic reactions in patients with seasonal or perennial rhinoconjunctivitis mediated by airborne allergens can be effectively assessed with the conjunctival provocation test (CPT). The CPT is a fast and easy diagnostic procedure that challenges the ocular mucosa with instillations of allergen solutions into the conjunctival region. This paper aimed to investigate the possible influence of repeated diagnostic CPT procedures on the patient's clinical presentation, i.e. to analyze desensitization effects caused by diagnostic solutions and to show the reproducibility of CPT results. Methods: Treatment progress in 120 placebo-treated patients from 2 immunotherapeutic dose-finding studies was estimated and documented, as based on the CPT which was applied at 4 visits with intervals of 4, 8 and 16 weeks. High-resolution digital photos collected as part of the CPT documentation were analyzed by an external observer and by digital analysis software to determine conjunctival redness, completely independent of the subjectivity of investigators and patients. Results: Two extremal scenarios of the redness changes were considered after provocation with 10,000 standard quality units/ml. A maximal decrease of about 3% (t test: p = 0.0002; U test: p = 0.001) and a minimal decrease of about 1% (t test: p = 0.254; U test: p = 0.431) were found. Conclusions: The observed decrease in conjunctival hyperemia can be explained by local desensitization or by placebo effect. Due to the setup of both studies considered, we could not ascertain how these factors influence the decrease in redness. In order to attribute the observed effects to local conjunctival desensitization with certainty, further pilot studies are needed.

Conjunctival Provocation Test in Daily Practice: Four Ocular Symptoms Vs Ocular Pruritus Score System

Conjunctival Provocation Test in Daily Practice: Four Ocular Symptoms Vs Ocular Pruritus Score System

Altered Serum IgE and IgG4 Response to Dermatophagoides Pteronyssinus Allergens during Specific Immunotherapy

A T U R D A Y Baoqing Sun, MHA, Zheng Peiyan; The First Affiliated Hospital of Guangzhou, Guangzhou, China, State Key Laboratory of Respiratory Disease, National Clinical Center for Respiratory Diseases, Guangzhou Institute of Respiratory Diseases, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China. RATIONALE: We investigated the changes in serum-specific IgE (sIgE) and IgG4 (sIgG4) against house dustmite (HDM) and its components Der p 1 and Der p 2 during specific immunotherapy (SIT), and evaluated the clinical efficacy thereof. METHODS: We retrospectively analyzed 51 HDM-sensitized children aged 5 to 16 years diagnosed with allergic rhinitis and/or asthma, following 36 monthsofSIT.Wealsocollecteddata fromacontemporarycontrol cohort of 50 patients administered routine medications for HDM allergy. . In the test cases, we recorded the sIgE and sIgG4 levels against thewhole allergen ofHDM(Der p), Der p 1 and Der p 2 at baseline and at 6, 12, 24 and 36 months of SIT. RESULTS: The serum sIgE response increased up to 6 months of SIT, but subsequently declined. At 36 months, the anti-Der p 1 and anti-Der p 2 sIgEs plummeted below the baseline. During SIT, the increased serum sIgG4 responsewas the greatest against Der p, followed byDer p 1 and Der p 2. The decline in sIgE/sIgG4 ratio for Der 1 was higher than for the other allergensmaximumdecline. Comparedwith older children, children aged 5 to 8 manifested a clearer sIgG4 response, especially against Der p 1 and Der p 2 versus Der p. CONCLUSIONS: SIT for HDM stimulated an early sIgE and sIgG4 response against HDM allergens. with a progressive decline in the ratio of sIgE/sIgG4, especially against Der p 1. Younger children may manifest a more rapid response to SIT than older ones. S 197 Conjunctival Provocation Test in Daily Practice: Four Ocular Symptoms Vs Ocular Pruritus Score System

XXIV World Allergy Congress 2015

XXIV World Allergy Congress 2015

Conjunctival Provocation Tests: A Predictive Factor for Patients' Seasonal Allergic Rhinoconjunctivitis Symptoms

No parameters currently exist that can reliably predict the impact of preseasonal immunotherapy on the symptoms occurring during the season. The purpose of our studies was to prove a correlation between preseasonal conjunctival allergen challenge and coseasonal primary clinical endpoints using the total combined score, ie, a combination of symptoms and medication score, as the primary outcome parameter. Twelve weeks before both the birch and the grass pollen seasons, 2 separate prospective, double-blind, randomized, controlled studies were conducted followed by posttrial observations for each study during the active season. In the studies, patients who reacted to conjunctival allergen challenge were treated with sublingual immunotherapy tablets that contain either birch and/or alder or grass pollen allergoids. In all, 158 patients were included in the grass and 160 in the tree pollen study; of these, 100 and 109 patients, respectively, took part in the posttrial observations. When comparing patients with and without a positive reaction in the final conjunctival allergen challenge, the results revealed a significant difference in the total combined score (grass: P < .001; birch: P = .025). The same applied to the rescue medication score (P = .005; P = .025). A significant difference regarding the rhinoconjunctivitis symptom score was shown in the grass pollen study (P = .002), and the difference of well days was significant in the tree pollen study (P = .049). When comparing patients based on their reaction to allergen challenge after immunotherapy, each study leads to similarly significant results. Therefore, conjunctival allergen challenge can be used effectively as a parameter to predict allergic rhinoconjunctivitis symptoms during the season in patients treated with preseasonal sublingual immunotherapy tablets. Whether this can be transferred to untreated patients needs to be determined.

Comparing safety of abrasion and tape-stripping as skin preparation in allergen-specific epicutaneous immunotherapy

Comparing safety of abrasion and tape-stripping as skin preparation in allergen-specific epicutaneous immunotherapy