Immunologic effect and tolerability of intra-seasonal subcutaneous immunotherapy with an 8-day up-dosing schedule to 10,000 standardized quality-units: a double-blind, randomized, placebo-controlled trial.
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 IgG(4), 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 IgG(4) levels) occurred with SCIT versus placebo at week 9 (IgE-blocking factor, P = 0.0017; IgG(4,)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 (χ(2) test, P < 0.0001). No significant difference was observed between groups in the incidence of systemic reactions (7.1% SCIT vs 5.6% placebo; χ(2) 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.
Center for Rhinology and Allergology, Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Mannheim, Wiesbaden, Germany. oliver.pfaar@allergiezentrum.org
Oliver
O
Pfaar
Hendrik
H
Wolf
Ludger
L
Klimek
Jörg
J
Schnitker
Eike
E
Wüstenberg
D000293:Adolescent; D000328:Adult; D000368:Aged; D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology; D003233:Conjunctivitis, Allergic / Q000276:immunology / Q000628:therapy*; D004306:Dose-Response Relationship, Immunologic; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods*; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D010936:Plant Extracts / Q000008:administration & dosage / Q000276:immunology; D006109:Poaceae / Q000276:immunology; D011058:Pollen / Q000276:immunology; D017410:Practice Guidelines as Topic; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology / Q000628:therapy*; D012621:Seasons; D012434:Secale / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D000485:Allergens; D007074:Immunoglobulin G; D010936:Plant Extracts; D007073:Immunoglobulin E