Abstract
Background
International guidelines recommend that allergen-specific immunotherapy for pollen-induced
rhinoconjunctivitis is initiated preseasonally. However, because subjects often present
to physicians with allergy symptoms during the pollen season, “within-season” initiation
of specific immunotherapy is of special interest.
Objective
We evaluated the immunomodulatory effects and tolerability of subcutaneous immunotherapy
(SCIT) with Standardized Quality (SQ) 6-grass mix and rye allergen extract, using
an 8-day intra-seasonal up-dosing schedule to 10,000 SQ-units (SQ-U).
Methods
In a 9-week, multicenter, randomized, double-blind, placebo-controlled trial, adults
(mean age, 34.6 years; 99.3% whites) with grass pollen–induced rhinoconjunctivitis
(mean disease duration, 15.1 years) were randomized 3:1 to receive SCIT or placebo.
Treatment was initiated during the 2008 pollen season, with an 8-day up-dosing from
100 to 10,000 SQ-U (6 daily injections) followed by 2 maintenance injections of 10,000
SQ-U at intervals of 2 and 4 weeks, respectively. The primary end point examined immunologic
effects, assessing the difference in IgE-blocking factor (serum components competing
with IgE for allergen binding) between SCIT and placebo at week 9. Secondary/explorative
end points included the difference in IgE-blocking factor, specific IgG4, and specific IgE at various times. Tolerability (adverse events, local and systemic
allergic reactions) of the up-dosing schedule was also evaluated.
Results
Of the 148 treated subjects 144 (SCIT n = 109; placebo n = 35) were analyzed for the
primary parameter. Immunologic response (significantly higher increase in IgE-blocking
factor and IgG4 levels) occurred with SCIT versus placebo at week 9 (IgE-blocking factor, P = 0.0017; IgG4, P = 0.0215). Significant differences were observed as early as week 3. AEs were reported
in 60.7% of SCIT- and 30.6% of placebo-treated subjects, with no treatment-related
serious AEs. Local allergic reactions occurred in 46.4% of SCIT and 8.3% of placebo
subjects (χ2 test, P < 0.0001). No significant difference was observed between groups in the incidence
of systemic reactions (7.1% SCIT vs 5.6% placebo; χ2 test, P = 0.7413).
Conclusions
This trial provides the first description of short (8-day) intra-seasonal up-dosing
with SCIT, which induced immunologic effects after only 3 weeks, and was generally
well tolerated, although it induced a marked increase in the rate of local reactions
compared with placebo. ClinicalTrials.gov identifier NCT00807547; ALK trial ID SHX0562.
Key words
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Article info
Publication history
Accepted:
September 10,
2012
Footnotes
Data from this article were published, in part, in abstract form as Klimek L, Wolf H, Pfaar O, Wüstenberg E. Allergy. 2010;65(Suppl 92):264–265 (poster at European Academy of Allergy and Clinical Immunology Congress 2010, London, United Kingdom); and Pfaar O, Wolf H, Liefold N, Schnitker J, Wüstenberg, E Klimek L. Allergo J. 2009;18:S29–S30 (oral presentation at Fourth German Allergy Congress 2009, Berlin, Germany).
Identification
Copyright
© 2012 Elsevier HS Journals, Inc. Published by Elsevier Inc. All rights reserved.
