A randomized, 5‐arm dose finding study with a mite allergoid <scp>SCIT</scp> in allergic rhinoconjunctivitis patients

Pfaar, Oliver; Nell, Marja J.; Boot, J. D.; Versteeg, Serge A.; Ree, Ronald van; Roger, Albert; Riechelmann, Herbert; Sperl, Annette; Elberink, J. N. G. Oude; Diamant, Zuzana; Bachert, Claus

doi:10.1111/all.12860

Cited by 47 publications

(36 citation statements)

References 30 publications

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“…In PQBirch204, the shape of the dose response curve showed that the highest dose of 27 300 SU was approaching a “plateau” (Figures and ). Nonmonotonic curves may occur with a sublingual immunotherapy (SLIT) and allergoid house dust mite SCIT . Further assurance about the reproducibility of this method of analysis is confirmed by the overlapping of the mean TSS scores from the PQBirch203 on the PQBirch204 MCP‐Mod dose response curves.…”

Section: Discussionmentioning

confidence: 93%

“…Efficacy of allergen immunotherapy (AIT) is related to the cumulative dose (CD) of the allergen or allergoid for symptom control and immunological changes. No consensus exists on the best method to select the optimal effective and tolerable CD.…”

Section: Introductionmentioning

confidence: 99%

“…Dose response curves in studies of AIT products to date are either monotonic (exponential), or nonmonotonic (higher dose less effective than the lower) . In either case, the ideal study design comprises a wide range of CDs and sufficient subjects to allow the dose response curve to be tested.…”

Section: Introductionmentioning

confidence: 99%

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

Worm

Higenbottam

Pfaar

et al. 2018

Allergy

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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.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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

Worm

Higenbottam

Pfaar

et al. 2018

Allergy

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“…Allergen titration should be limited to research settings, therapy control (testing the response to certain treatments, if continuation of therapy needs to be decided), dose finding processes (to determine the sensitivity threshold of each allergen in research settings), or patients with extremely high grades of sensitization, in whom the standardized concentration might evoke anaphylaxis and asthma attacks …”

Section: Resultsmentioning

confidence: 99%

EAACI Position paper on the standardization of nasal allergen challenges

Augé

Vent

Agache

et al. 2018

Allergy

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Nasal allergen challenge (NAC) is an important tool to diagnose allergic rhinitis. In daily clinical routine, experimentally, or when measuring therapeutic success clinically, nasal allergen challenge is fundamental. It is further one of the key diagnostic tools when initiating specific allergen immunotherapy. So far, national recommendations offered guidance on its execution; however, international divergence left many questions unanswered. These differences in the literature caused EAACI to initiate a task force to answer unmet needs and find a consensus in executing nasal allergen challenge. On the basis of a systematic review containing nasal allergen challenges of the past years, task force members reviewed evidence, discussed open issues, and studied variations of several subjective and objective assessment parameters to propose a standardized way of a nasal allergen challenge procedure in clinical practice. Besides an update on indications, contraindications, and preparations for the test procedure, main recommendations are a bilaterally challenge with standardized allergens, with a spray device offering 0.1 mL per nostril. A systematic catalogue for positivity criteria is given for the variety of established subjective and objective assessment methods as well as a schedule for the challenge procedure. The task force recommends a unified protocol for NAC for daily clinical practice, aiming at eliminating the previous difficulty of comparing NAC results due to unmet needs.

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“…The safety profile of allergen immunotherapy (AIT) has been thoroughly documented in well-designed clinical studies (8)(9)(10) . Also, recently, the Immunotherapy Interest Group of the European Academy of Allergy and Clinical Immunology (EAACI)…”

Section: Discussionmentioning

confidence: 99%