1. HATSJOE Study Symptomatic treatment of pollen-related allergic rhinoconjunctivitis in children: a randomized controlled trial.

2. Background – Research Questions
Allergic rhinitis/rhinoconjunctivitis (AR) ~12% prevalence in children
Intranasal corticosteroids (INCS) VS Antihistamines
Children (especially <12 years)
Oculair symptoms
INCS daily VS INCS on demand
Physician advise vs patient use

3. Participants Children aged 6-18 years old From GP medical file:
ICPC R97
ATC R01AC, R01AD, R06AA, R06AE, R06AX or S01GX
Sensitization to grass pollen (determined by CAP RAST or Skin Prick test, positive test: class ≥2).
A minimum retrospective AR symptom score of 7/21
Written informed consent

4. Intervention Cohort 1: April – June 2013 Cohort 2: April – July 2014
Randomization to:
INCS daily (on a daily basis: Fluticasone propionate nasal spray, < 12 years old 100 mcg/day , ≥12 years old 200 mcg/day)
INCS on demand (used when needed: Fluticasone propionate, as described in INCS continuous)
Antihistamines on demand (used when needed: Levocetirizine dihydrochloride (diHCl) tablet, 5 mg/day)

5. Outcome measures Primary outcome measure
Percentage of symptom free days
(4 nose symptoms and 3 eye symptoms, recorded in the daily diary)
Secondary outcomes measures
1) mean daily allergy symptom score
2) mean eye symptom score
3) mean nose symptom score
4) mean daily allergy symptom score per symptom (total of 7)
5) percentage of symptom free days for each symptom separately
6) proportion of rescue medication-free days and use of rescue medication
7) disease-specific quality of life
8) patient preference of medication over the total period of three months

6. Table 1. Baseline Characteristics
INCS Continuous (n=50)
INCS
on demand
(n=52)
Antihistamines
(n=48)
Boys N(%) 22
(44) 30
(57.7) 26
(54.2)
Age (y) Mean (SD)
12.1
(3.3)
11.8
(3.1)
11.0
Retrospective symptom score1
Total [mean (SD)]2
4.6
(3.2)
5.2
(2.6)
5.4
(3.6)
Nose [mean (SD)]3
2.2
(2.3)
2.1
(2.2)
2.9
Eye [mean (SD)]4
2.4
(2.7)
3.1
(2.0)
(2.5)
Asthma N(%) 8
(17.4) 5
(9.8)
Grass sensitization class >2 N(%) 31
(62) 36
(69.2)
(62.5)
Birch pollen sensitization N(%)
(60)
(59.6) 28
(58.3)
HDM sensitization N(%) 25
(50)
(53.8) 24
Current use of secondary care for AR5 N(%) 6
(12.5) 4
(7.8)
(8.7)
Cohort 1 N(%) 18
(36) 16
(30.8) 17
(35.4)
Participants with evaluable days, ITT population N(%) 45
(90) 41
(88.5) 46
(85.4)
1 (n=12 missing) 2 (scale 0-21)3 (scale 0-12)4(scale 0-9) 5(n=5 missing)

7. Medication use Antihistamine: 43 tablets (on average for 91 days)
INCS daily: 90% of the days (SD 16)
23.1 ml fluticasone (± 257 sprays)
INCS on demand: 30% of the days (SD 21)
9.1 ml fluticasone (± 102 sprays)

8. Results % Symptom free days INCS daily: 22% INCS on demand : 30%
Antihistamines: 15%
Clinically relevant difference set at 10%-point in symptom free days
INCS on the demand vs INCS daily
8% in favour of INCS on demand (95%CI: -5 to +21%)
(due to significantly better score on eye symptoms)
INCS daily vs Antihistamine
7% in favour of INCS daily (95%CI: -6% to +19%)

9. Conclusions INCS daily is not superior to INCS on demand
Antihistamines are not superior to INCS daily
On demand use of INCS leads to 61% less corticosteroid use

10. Questions?

11. Flowchart

12. Measurements Daily online diary PRQLQ/AdolRQLQ (Juniper et al.1,2)
Patient preference questionnaire
1 Juniper E, Howland W, Roberts N, Thompson A, King D. Measuring quality of life in children with rhinoconjunctivitis. . J Allergy Clin Immunol 1998; 101:
2 Juniper E, Guyatt G, Dolovich J. Assessment of quality of life in adolescents with allergic rhinoconjunctivitis: development and testing of a questionnaire for clinical trials. J Allergy Clin Immunol 1994; 93:

13. Statistics Two comparisons: INCS daily vs INCS on demand
INCS daily vs antihistamines on demand
Treatment effects will be tested 2-sided with a significance level of 2,5% using an ANCOVA.
Covariates
Age Gender
Grass sensitization class Birch pollen sensitization
HDM sensitization Cohort
Baseline symptom sum score at entry into study
Current use of secondary care for their AR

14. INCS D vs Antihistamine
Table 2. Results of the univariate analyses of the symptom free days (intention-to-treat in pollenseason)
INCS daily
INCS on demand
INCS D vs INCS OD
Antihistamine
INCS D vs Antihistamine
mean (95% CI)
P-value
P-Value
Percentage symptom free days
22 (14-30)
30 (22-38)
0,062
15 ( )
0,815
Percentage well days
52 (43-62)
60 (51-69)
0,1
46 (38-54)
0,72
Percentage nose symptom free days
total
31 (21-40)
36 (27-45)
0,431
19 ( )
0,151,3,7
sneezing
57 (47-67)
54 (44-64)
0,915
38 (29-47)
0,0171,2,3,6,7
nose blockage
62 (52-73)
58 (49-68)
0,932
50 (41-60)
0,359
runny nose
67 (58-76)
72 (65-79)
0,134
51 (43-60)
0,0711,3,7
itching nose
49 (40-59)
59 (49-69)
0,192
41 (32-49)
0,356
Percentage eye symptom free days
40 (31-50)
56 (47-65)
0,0051,2,4,6
0,0717
itching eyes
43 (33-53)
61 (52-69)
0,0021,2,3,4,6,7
52 (44-60)
0,0224,5,6
redness
71 (62-81)
80 (74-87)
0,0222,6
78 (70-86)
0,0544,5,6
tearing
68 (59-77)
73 (64-81)
0,165
70 (62-77)
0,382
P<0.05 in Other scenario’s: 1 Pollen season Per Protocol(PP); 2 Grass season Intention to Treat (I.T.T.); 3 Grass season P.P.; 4 Birch season I.T.T.; 5 Birch season P.P.; 6 All days I.T.T.; 7 All days P.P.

15. INCS D vs Antihistamine
Table 3. Symptomscores
Table 3. Diary allergic symptomscores, per randomization group
INCS daily
INCS on demand
INCS D vs INCS OD
Antihistamine
INCS D vs Antihistamine
Mean
(95% CI)
P-value
Mean Daily Symptom Score (Range 0-21)
3,90
(3,03 - 4,7)
3,26
(2,51 - 4,01)
0,840
4,63
(3,81 – 5,4)
0,640
Mean Nose Symptom Score (Range 0-12)
2,20
(1,69 - 2,71)
2,08 (1,63 - 2,54)
0,416
3,14
(2,62 – 3,65)
0,0501,2,3,6,7
Mean Eye Symptom Score (Range 0-9)
1,69
(1,28 - 2,11)
1,18
(0,84 - 1,52)
0,0092,6
1,50
(1,09 – 1,90)
0,1174,5
P<0.05 in Other scenario’s: 1 Pollen season Per Protocol(PP); 2 Grass season Intention to Treat (I.T.T.); 3 Grass season P.P.; 4 Birch season I.T.T.; 5 Birch season P.P.; 6 All days I.T.T.; 7 All days P.P.