219 / 236
scheduled time the next day. If you don’t take [the product] for
more than one day, contact your health provider before
restarting.’’
2,3,40
CAN SLIT ALLERGENS BE COMBINED?
The European experience suggests that distinct SLIT tablets
(grass and ragweed) can be administered separately to the same
patient. One open-label, controlled, 4-parallel-group, randomized
study showed favorable results in patients sensitized to grass and
birch with 2 SLIT products
14
; another reported favorable results
in patients given SLIT with grass plus olive extract.
27
Ongoing
studies suggest that dual administration of SLIT products can
be well tolerated. However, there are no published data on the
concomitant use of the 3 products approved in the United States
with each other or with SCIT, and the PIs state that concomitant
dosing might increase the likelihood of local or systemic adverse
reactions to either SCIT or SLIT.
WHAT ADVERSE EVENTS CAN OCCUR WITH SLIT?
Adverse reactions associated with SLIT can be local
or systemic. Local reactions, such as oral or mild
gastrointestinal symptoms, are fairly common, affecting up to
TABLE III.
Randomized trials comparing the clinical effects of SCIT and SLIT
Study, year
Allergen
(duration)
Patients
enrolled/dropouts
Age
range (y)
Main results
Piazza et al,
15
1993
Mite (2 y)
SCIT
5
17/0
SLIT
5
14/0
LNIT
5
12/0
Control
5
14/0
15-60 SLIT: decrease in symptoms at 3 mo but not 12-24 mo
SCIT: decrease in symptoms at 3, 12, and 24 mo; IgE, IgG, and IgG
4
changed only in SCIT. No change at all in LNIT.
Quirino et al,
16
1996
*
Grass (1 y)
SCIT
5
10/0
SLIT
5
15/0
18-60 Significant reduction in symptom and drug intake score in both
groups vs baseline. No change in IgE level. Increase in IgG level and
reduction of skin reactivity only in the SCIT group.
Mungan et al,
17
1999
Mite (1 y)
SCIT
5
15/0
SLIT
5
10/0
Placebo
5
11/0
18-65 Reduction in rhinitis score for SLIT and SCIT. Asthma score
reduction only for SCIT. Reduction in drug score for both SLIT and
SCIT. Reduction in SPT diameter only in the SCIT group.
Khinchi et al,
18
2002
*
Birch (2 y)
SCIT
5
24/5
SLIT
5
23/9
Placebo
5
24/9
18-60 Reduction in rhinitis score in SLIT and SCIT. No significant
difference between the 2 treatments, both superior to placebo.
Medication scores SLIT and SCIT decreased vs placebo. No change in QoL.
Mauro et al,
19
2007
Birch (4 mo) SCIT
5
23/8
SLIT
5
24/5
18-65 During pollen season, no SLIT-SCIT difference in symptoms plus drug
scores. Specific IgG
4
levels significantly increased with SCIT only.
Antunez et al,
20
2007
Mite (2 y)
SCIT
5
12/1
SLIT
5
11/1
8-17 Improvement in subjective evaluation and VAS in both groups. Increase in IgG
4
levels only for SCIT. Decreases IgE/IgG
4
levels in both.
Tahamiler et al,
21
2008
Mite (3
1
3 y) SCIT
5
96/NR
SLIT
5
97/NR
NR (adults) Decrease in symptom score and nasal provocation scores in both groups after 3 y
of treatment (greater in SCIT). Improvement maintained after 3 y only in SCIT.
Ventura et al,
22
2009
Cypress (1 y) SCIT
5
10
SLIT
5
10
18-65 Decrease in symptom scores in both groups (no value given): decrease in nasal
eosinophil counts in SLIT.
Eifan et al,
23
2010
Mite (1 y)
SCIT
5
16/2
SLIT
5
16/1
Drug
5
16/2
5-12 Significant reduction in total rhinitis and asthma scores, medication scores, VAS
scores, and skin reactivity for both SCIT and SLIT.
No difference between routes of administration.
Yukselen et al,
24
2011
Mite (1 y)
SCIT
5
10/1
SLIT
5
11/1
Placebo
5
11/0
7-14 Significant reduction in symptom and medication score vs baseline with both
treatments. SCIT is better than SLIT vs placebo.
Keles et al,
25
2011
*
Mite (1 y)
SCIT
5
15/2
SLIT
5
15/2
SCIT
1
SLIT
5
15/1
Drugs
5
15/3
5-12 Decreased asthma attacks and use of steroids at 4, 12, and 18 mo for SCIT and
SCIT plus SLIT at 12 mo only for SLIT. No change in VAS score for asthma
with SCIT or SIT alone.
QoL
, Quality of life;
NR
, not reported;
SCIT
, subcutaneous immunotherapy;
SLIT
, sublingual immunotherapy;
SPT
, skin prick test;
VAS
, visual analog scale.
*Double-blind double-dummy.
TABLE IV.
Optimal maintenance doses of allergen based on available dose-ranging studies
Author, year
Total patients randomized
Allergen/preparation
Optimal maintenance dose
Durham et al,
34
2006
855
Timothy grass/tablets
15
m
g of Phl p 5/d
Didier et al,
35
2007
628
5-Grass mix tablets
25
m
g/mL group 5/d
Creticos et al,
30
2014
784 AR/ARC
Ragweed tablets
12
m
g of Amb a 1/d
Bergmann et al,
31
2014
AR/ARC
Dust mite
28
m
g of Der p 1, 120
m
g of Der f 1 (500 IR)
Mosbech et al, 2014
32
and 2015
36
Asthma 604
AR 204
Dust mite tablet
6 SQ-HDM
6 SQ-HDM
Nolte et al,
33
2015
124
Dust mite tablets
12 DU
*
AR
, Allergic rhinitis;
ARC
, allergic rhinoconjunctivitis;
HDM
, house dust mite.
*Same product as the Mosbech et al studies but different dosing units.
J ALLERGY CLIN IMMUNOL
nnn
2015
LI ET AL
197