Recommended Topic Related To:

Grastek

"The U.S. Food and Drug Administration recently approved Oralair to treat allergic rhinitis (hay fever) with or without conjunctivitis (eye inflammation) that is induced by certain grass pollens in people ages 10 through 65 years. Oralair is the f"...

Grastek

CLINICAL PHARMACOLOGY

Mechanism Of Action

The precise mechanisms of action of allergen immunotherapy are not known.

Clinical Studies

The efficacy of GRASTEK in the treatment of allergic rhinitis with or without conjunctivitis in Timothy grass pollen allergic subjects 5 years of age and older, with or without mild asthma, was evaluated during the first grass pollen season in two trials of approximately 24 weeks treatment duration. The sustained effect of GRASTEK was evaluated in one trial conducted over 5 grass pollen seasons. All three trials were randomized, double-blind, parallel group, multicenter clinical trials. Subjects had a history of grass pollen induced rhinitis with or without conjunctivitis and sensitivity to Timothy grass pollen as determined by specific testing (IgE). In these three studies, subjects initiated GRASTEK or placebo approximately 12 weeks prior to the pollen season. In the long-term study, subjects received GRASTEK or placebo daily for 3 consecutive years and were followed for 2 years without treatment.

Efficacy was established by self-reporting of rhinoconjunctivitis daily symptom scores (DSS) and daily medication scores (DMS). Daily rhinoconjunctivitis symptoms included four nasal symptoms (runny nose, stuffy nose, sneezing, and itchy nose), and two ocular symptoms (gritty/itchy eyes and watery eyes). The rhinoconjunctivitis symptoms were measured on a scale of 0 (none) to 3 (severe). Subjects in clinical trials were allowed to take symptom-relieving medications (including systemic and topical antihistamines and topical and oral corticosteroids) as needed. The daily medication score measured the use of standard open-label allergy medications. Predefined values were assigned to each class of medication. Generally, systemic and topical antihistamines were given the lowest score, topical steroids an intermediate score, and oral corticosteroids the highest score. The sums of the DSS and DMS were combined into the Total Combined Score (TCS) which was averaged over the entire grass pollen season.

First Season Efficacy

Adults and Children

This placebo-controlled trial evaluated 1501 subjects 5 through 65 years of age (approximately 80% were 18 years and older) comparing GRASTEK (N=752) and placebo (N=749) administered as a sublingual tablet daily for approximately 24 weeks. The subject population was 84% White, 9% African American and 4% Asian. The majority of subjects were male (52%). In this study, approximately 25% of subjects had mild, intermittent asthma and 85% of all subjects were sensitized to other allergens in addition to grass pollen. Subjects with a clinical history of symptomatic allergies to non-grass pollen allergens that required treatment during the grass pollen season were excluded from the studies. All treatment groups were balanced with regard to baseline characteristics.

Subjects treated with GRASTEK had a decrease in the TCS throughout the grass pollen season compared to placebo-treated subjects. Similarly, the DSS and DMS were decreased in subjects treated with GRASTEK compared to placebo throughout the grass pollen season, and the TCS was decreased compared to placebo during the peak grass pollen season (see Table 3).

Table 3: Total Combined Scores (TCS), Rhinoconjunctivitis Daily Symptom Scores (DSS), and Daily Medication Scores (DMS) During the Grass Pollen Season

Endpoint* GRASTEK
(N)† Score‡
Placebo
(N)†Score‡
Treatment Difference
(GRASTEK - Placebo)
Difference Relative to Placebo§Estimate
(95% CI)
TCS
Entire Season

(629)
3.24

(672)
4.22
-0.98 -23%
(-36.0, -13.0)
TCS
Peak Season

(620)
3.33

(663)
4.67
-1.33 -29%
(-39.0, -15.0)
DSS
Entire Season

(629)
2.49

(672)
3.13
-0.64 -20%
(-32.0, -10.0)
DMS
Entire Season

(629)
0.88

(672)
1.36
-0.48 -35%
(-49.3, -20.8)
TCS=Total Combined Score (DSS + DMS); DSS=Daily Symptom Score; DMS=Daily Medication Score.
* Non-parametric analysis for TCS and DSS endpoints: Parametric analysis using zero-inflated lognormal model for DMS.
† Number of subjects in analyses.
‡ For TCS and DSS endpoints the group medians are reported, treatment difference and that relative to placebo is based on group medians. For DMS, the group means are reported and difference relative to placebo is based on estimated group means.
§ Difference relative to placebo computed as:
(GRASTEK - placebo)/placebo x 100.

Children

This double-blind clinical trial of approximately 24 weeks duration evaluated 344 pediatric subjects 5 to 17 years of age who were treated with either GRASTEK or placebo once daily. The subject population was 88% White, 7% African American, and 2% Asian. The majority (65%) of subjects were male. The mean age of subjects was 12.3 years. In this study, 26% of subjects had mild intermittent asthma and most subjects (89%) were sensitized to other allergens in addition to grass pollen. Subjects with a clinical history of symptomatic allergies to non-grass pollen allergens that required treatment during the grass pollen season were excluded from the studies. All treatment groups were balanced with regard to baseline characteristics.

Pediatric subjects treated with GRASTEK had a decrease in TCS throughout the grass pollen season compared to placebo treated subjects (see Table 4). Similarly, the DSS and DMS were decreased in GRASTEK compared to placebo throughout the grass pollen season.

Table 4: Total Combined Scores (TCS), Rhinoconjunctivitis Daily Symptom Scores (DSS) and Daily Medication Scores (DMS) During the Entire Grass Pollen Season

Endpoint* GRASTEK
(N=149)†+ Score‡
Placebo
(N=158)†+ Score‡
Treatment Difference (GRASTEK -Placebo) Difference Relative to Placebo§ Estimate (95% CI)
TCS 4.62 6.25 -1.63 -26%
(-38.2, -10.1)
DSS 3.71 4.91 -1.20 -24%
(-36.4, -9.1)
DMS 0.91 1.33 -0.42 -32%
(-57.7, 4.0)
TCS=Total combined score (DSS + DMS); DSS=Daily Symptom Score; DMS=Daily Medication Score.
* Parametric analysis using analysis of variance model for all endpoints.
† Number of subjects in analyses.
‡ The estimated group means are reported and difference relative to placebo is based on estimated group means.
§ Difference relative to placebo computed as: (GRASTEK - placebo)/placebo x 100.

Sustained Effect

Adult Subjects 18 Years and Older

The sustained effect of GRASTEK was measured in a 5-year double-blind study. The study included 634 randomized subjects between 18 and 65 years of age. The subject population was 96% White, 2% Asian and 1% African American. The majority (59%) of subjects were male. The mean age of subjects was 34 years. Subjects received either GRASTEK or placebo daily for 3 consecutive years and were then observed for 2 subsequent years during which they did not receive study drug. Subjects treated with GRASTEK had a decrease in TCS throughout the grass pollen season during the three years of active treatment. This effect was sustained during the grass pollen season in the first year after discontinuation of GRASTEK (see Table 5), but not in the second year.

Table 5: Rhinoconjunctivitis Total Combined Score (TCS), Daily Symptom Score (DSS), and Daily Medication Score (DMS) During the Entire Grass Pollen Season from the 5-Year Study

Endpoint Difference Relative to Placebo*
(95% CI)
Treatment Year 1
N=568†
Treatment Year 2‡
N=316†
Treatment Year 3
N=287†
Post Treatment Year 1
N=257†
TCS -34.2%
(-42.0%, -26.3%)
-40.9%
(-51.8%, -29.5%)
-34.0%
(-45.5%, -21.4%)
-27.2%
(-39.9%, -12.4%)
DSS -31.2%
(-38.8%, -23.4%)
-36.2%
(-46.5%, -26.2%)
-29.0%
(-40.3%, -16.3%)
-26.2%
(-37.6%, -12.2%)
DMS -38.4%
(-49.8%, -26.5%)
-45.5%
(-60.4%, -28.2%)
-40.1%
(-55.4%, -21.2%)
-28.6%
(-46.3%, -6.0%)
TCS=Total Combined Score
(DSS + DMS); DSS=Daily Symptom Score; DMS=Daily Medication Score.
* Difference relative to placebo computed as:
(GRASTEK - placebo)/placebo x 100.
† Number of subjects in analyses.
‡ Study extended from 1 to 5 years
(site closures, subject unwillingness to participate beyond 1 year).

Last reviewed on RxList: 5/1/2014
This monograph has been modified to include the generic and brand name in many instances.

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